Publications - All publications https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Bcontroller%5D=Publications&cHash=da7a47b09b0e8fbc494e48903cf8d0f2 en-us PURE Extension typo3support@science.au.dk (Web Department) 30 <![CDATA[Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=bad91077-f0b0-4028-8e0a-b8371ab4ce41&tx_pure_pure5%5BshowType%5D=pub&cHash=daead912324f266f0bbf01b772b24807 Bauer, M., Glenn, T., Achtyes, E. D., et al. Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.

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Research Wed, 01 Dec 2021 23:03:34 +0100 bad91077-f0b0-4028-8e0a-b8371ab4ce41
<![CDATA[Pulmonary maternal immune activation does not cross the placenta but leads to fetal metabolic adaptation]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=0a4c0c81-fa34-4acb-9aa1-39a1c0915c75&tx_pure_pure5%5BshowType%5D=pub&cHash=2707599be816d877d31dde88ca724469 Hansen, S. S. K., Krautz, R., Rago, D., et al. The fetal development of organs and functions is vulnerable to perturbation by maternal inflammation which may increase susceptibility to disorders after birth. Because it is not well understood how the placenta and fetus respond to acute lung- inflammation, we characterize the response to maternal pulmonary lipopolysaccharide exposure across 24 h in maternal and fetal organs using multi-omics, imaging and integrative analyses. Unlike maternal organs, which mount strong inflammatory immune responses, the placenta upregulates immuno-modulatory genes, in particular the IL-6 signaling suppressor Socs3. Similarly, we observe no immune response in the fetal liver, which instead displays metabolic changes, including increases in lipids containing docosahexaenoic acid, crucial for fetal brain development. The maternal liver and plasma display similar metabolic alterations, potentially increasing bioavailability of docosahexaenoic acid for the mother and fetus. Thus, our integrated temporal analysis shows that systemic inflammation in the mother leads to a metabolic perturbation in the fetus.

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Research Sat, 01 Jun 2024 23:03:34 +0200 0a4c0c81-fa34-4acb-9aa1-39a1c0915c75
<![CDATA[Approaches to embryonic neurodevelopment]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=9445f459-b6b7-45c0-ac3f-d778a0c31df3&tx_pure_pure5%5BshowType%5D=pub&cHash=eeac32c05a2d0cab50571221c7fc3523 Rafati, A. H., Joca, S., Vontell, R. T., Wegener, G., Ardalan, M. The development of the human central nervous system initiates in the early embryonic period until long after delivery. It has been shown that several neurological and neuropsychiatric diseases originate from prenatal incidents. Mathematical models offer a direct way to understand neurodevelopmental processes better. Mathematical modelling of neurodevelopment during the embryonic period is challenging in terms of how to 'Approach', how to initiate modelling and how to propose the appropriate equations that fit the underlying dynamics of neurodevelopment during the embryonic period while including the variety of elements that are built-in naturally during the process of neurodevelopment. It is imperative to answer where and how to start modelling; in other words, what is the appropriate 'Approach'? Therefore, one objective of this study was to tackle the mathematical issue broadly from different aspects and approaches. The approaches were divided into three embryonic categories: cell division, neural tube growth and neural plate growth. We concluded that the neural plate growth approach provides a suitable platform for simulation of brain formation/neurodevelopment compared to cell division and neural tube growth. We devised a novel equation and designed algorithms that include geometrical and topological algorithms that could fit most of the necessary elements of the neurodevelopmental process during the embryonic period. Hence, the proposed equations and defined mathematical structure would be a platform to generate an artificial neural network that autonomously grows and develops.

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Research Mon, 01 Jul 2024 23:03:34 +0200 9445f459-b6b7-45c0-ac3f-d778a0c31df3
<![CDATA[Regulation of mitochondrial dysfunction by estrogens and estrogen receptors in Alzheimer's disease]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=df6e16fb-0bc2-43d7-acee-24dbf04f7ec3&tx_pure_pure5%5BshowType%5D=pub&cHash=841bb7aa56555f4f96448d087c7332ad Arjmand, S., Ilaghi, M., Sisakht, A. K., et al. Alzheimer's disease (AD) is a neurodegenerative disorder that primarily manifests itself by progressive memory loss and cognitive decline, thus significantly affecting memory functions and quality of life. In this review, we proceed from the understanding that the canonical amyloid-β hypothesis, while significant, has faced setbacks, highlighting the need to adopt a broader perspective considering the intricate interplay of diverse pathological pathways for effective AD treatments. Sex differences in AD offer valuable insights into a better understanding of its pathophysiology. Fluctuation of the levels of ovarian sex hormones during perimenopause is associated with changes in glucose metabolism, as a possible window of opportunity to further understand the roles of sex steroid hormones and their associated receptors in the pathophysiology of AD. We review these dimensions, emphasizing the potential of estrogen receptors (ERs) to reveal mitochondrial functions in the search for further research and therapeutic strategies for AD pharmacotherapy. Understanding and addressing the intricate interactions of mitochondrial dysfunction and ERs potentially pave the way for more effective approaches to AD therapy.

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Research Mon, 27 May 2024 23:03:34 +0200 df6e16fb-0bc2-43d7-acee-24dbf04f7ec3
<![CDATA[Subanesthetic S-ketamine does not acutely alter striatal dopamine transporter binding in healthy Sprague Dawley female rats]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=838c6ce3-2282-49d5-8f46-486f2d31d1aa&tx_pure_pure5%5BshowType%5D=pub&cHash=d7e204890fd6083c4a2c907e457358c1 Bærentzen, S. L., Thomsen, J. B., Thomsen, M. B., et al. Major depressive disorder is one of the most prevalent mental health disorders, posing a global socioeconomic burden. Conventional antidepressant treatments have a slow onset of action, and 30% of patients show no clinically significant treatment response. The recently approved fast-acting antidepressant S-ketamine, an N-methyl-D-aspartate receptor antagonist, provides a new approach for treatment-resistant patients. However, knowledge of S-ketamine's mechanism of action is still being established. Depressed human subjects have lower striatal dopamine transporter (DAT) availability compared to healthy controls. Rodent studies report increased striatal dopamine concentration in response to acute ketamine administration. In vivo [ 18F]FE-PE2I ([ 18F]-(E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β-(4'-methyl-phenyl) nortropane) positron emission tomography (PET) imaging of the DAT has not previously been applied to assess the effect of acute subanesthetic S-ketamine administration on DAT availability. We applied translational in vivo [ 18F]FE-PE2I PET imaging of the DAT in healthy female rats to evaluate whether an acute subanesthetic intraperitoneal dose of 15 mg/kg S-ketamine alters DAT availability. We also performed [ 3H]GBR-12935 autoradiography on postmortem brain sections. We found no effect of acute S-ketamine administration on striatal DAT binding using [ 18F]FE-PE2I PET or [ 3H]GBR-12935 autoradiography. This negative result does not support the hypothesis that DAT changes are associated with S-ketamine's rapid antidepressant effects, but additional studies are warranted.

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Research Mon, 01 Jul 2024 23:03:34 +0200 838c6ce3-2282-49d5-8f46-486f2d31d1aa
<![CDATA[The Interplay between the Estrogen Ensemble and Antidepressants: A Search for Therapeutic Insights]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=4f0f7726-4104-473a-ba41-44ebaf0a470d&tx_pure_pure5%5BshowType%5D=pub&cHash=56cfb90abb0e22b4a1e25777fc621f53 Arjmand, S. Research Mon, 01 Jan 2024 23:03:34 +0100 4f0f7726-4104-473a-ba41-44ebaf0a470d <![CDATA[Mice lacking interleukin-18 gene display behavioral changes in animal models of psychiatric disorders: Possible involvement of immunological mechanisms]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=24fda937-d689-4669-b1a1-d53f83605e21&tx_pure_pure5%5BshowType%5D=pub&cHash=af06b1de27d84b0f95cae85e2316ae03 Lisboa, S. F. S., Issy, A. C., Biojone, C., et al. Research Mon, 01 Jan 2018 23:03:34 +0100 24fda937-d689-4669-b1a1-d53f83605e21 <![CDATA[Elastase-2 Knockout Mice Display Anxiogenic- and Antidepressant-Like Phenotype: Putative Role for BDNF Metabolism in Prefrontal Cortex]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=01b80576-e892-4668-bf22-5b71c9f33446&tx_pure_pure5%5BshowType%5D=pub&cHash=de86331eba27c9899808438809a5aa0a Diniz, C. R. A. F., Becari, C., Lesnikova, A., et al. Research Mon, 01 Jan 2018 23:03:34 +0100 01b80576-e892-4668-bf22-5b71c9f33446 <![CDATA[Antidepressant-like effect of losartan involves TRKB transactivation from angiotensin receptor type 2 (AGTR2) and recruitment of FYN]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=54e89c4d-f359-42e5-8899-c7c68ef71f3c&tx_pure_pure5%5BshowType%5D=pub&cHash=8b50995656c979dcc9464ab430993478 Diniz, C. R. A. F., Casarotto, P. ., Fred, S. M., Biojone, C., Castren, E., Joca, S. Research Mon, 01 Jan 2018 23:03:34 +0100 54e89c4d-f359-42e5-8899-c7c68ef71f3c <![CDATA[Dual mechanism of TRKB activation by anandamide through CB1 and TRPV1 receptors]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=a29c8684-f255-48ce-84d2-4cd053f70fb2&tx_pure_pure5%5BshowType%5D=pub&cHash=8eaa0ee3c137cba038a87f198e00c2ed Diniz, C. R. A. F., Biojone, C., Joca, S., et al. Research Tue, 01 Jan 2019 23:03:34 +0100 a29c8684-f255-48ce-84d2-4cd053f70fb2 <![CDATA[Reduced P2X receptor levels are associated with antidepressant effect in the learned helplessness model]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=a0513fec-94c0-476d-89e6-63e1ffe421f7&tx_pure_pure5%5BshowType%5D=pub&cHash=107cd8c12cfecfb68527c421e8035010 Ribeiro, D. E., Casarotto, P. ., Stanquini, L., et al. Research Tue, 01 Jan 2019 23:03:34 +0100 a0513fec-94c0-476d-89e6-63e1ffe421f7 <![CDATA[New insights into the involvement of serotonin and BDNF-TrkB signalling in cannabidiol's antidepressant effect]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=e155e580-5c42-4a90-a90f-a92bde8dfc44&tx_pure_pure5%5BshowType%5D=pub&cHash=d9ada2c4cede0ad043a8da9737c23063 Guldager, M. B., Biojone, C., Rodrigues Da Silva, N., Dornela Godoy, L., Joca, S. Research Mon, 01 Jan 2024 23:03:34 +0100 e155e580-5c42-4a90-a90f-a92bde8dfc44 <![CDATA[Excessive sucrose consumption reduces synaptic density and increases cannabinoid receptors in Göttingen minipigs]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=34963b4a-f3c1-4873-99c3-f143a4675e0d&tx_pure_pure5%5BshowType%5D=pub&cHash=5b4900f0553baf1ccf38e90dbef86dec Bærentzen, S. L., Thomsen, M., Alstrup, A. K. O., et al. Diets high in sucrose and fat are becoming more prevalent the world over, accompanied by a raised prevalence of cardiovascular diseases, cancers, diabetes, obesity, and metabolic syndrome. Clinical studies link unhealthy diets with the development of mental health disorders, particularly depression. Here, we investigate the effects of 12 days of sucrose consumption administered as 2 L of 25% sucrose solution daily for 12 days in Göttingen minipigs on the function of brain receptors involved in reward and motivation, regulating feeding, and pre- and post-synaptic mechanisms. Through quantitative autoradiography of cryostat sections containing limbic brain regions, we investigated the effects of sucrose restricted to a 1-h period each morning, on the specific binding of [3H]raclopride on dopamine D2/3 receptors, [3H]UCB-J at synaptic vesicle glycoprotein 2A (SV2A), [3H]MPEPγ at metabotropic glutamate receptor subtype 5 (mGluR5) and [3H]SR141716A at the cannabinoid receptor 1 (CB1). Compared to control diet animals, the sucrose group showed significantly lower [3H]UCB-J and [3H]MPEPγ binding in the prefrontal cortex. The sucrose-consuming minipigs showed higher hippocampal CB1 binding, but unaltered dopamine D2/3 binding compared to the control group. We found that the sucrose diet reduced the synaptic density marker while increasing CB1 binding in limbic brain structures, which may subserve maladaptive changes in appetite regulation and feeding. Further studies of the effects of diets and lifestyle habits on brain neuroreceptor and synaptic density markers are warranted.

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Research Sun, 01 Sep 2024 23:03:34 +0200 34963b4a-f3c1-4873-99c3-f143a4675e0d
<![CDATA[The efficacy of ball blankets on insomnia in depression in outpatient clinics]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=108cee4c-f918-4872-9675-0d4252d36bd8&tx_pure_pure5%5BshowType%5D=pub&cHash=77252f3d7a8aeca421ddccadc1fd6e02 Kristiansen, S. T., Videbech, P., Speed, M., Dionysopoulos, P., Bjerrum, M. B., Larsen, E. R. Many patients with depression report insomnia symptoms that profoundly affect their health and well-being. Non-pharmacological treatments of insomnia may be preferable for some patients. In this randomised crossover trial, we investigated the efficacy of the Protac Ball Blanket® on insomnia among patients with depression. Included patients (n = 45) were diagnosed with unipolar depression, and with subjective insomnia and poor sleep quality (Pittsburgh Sleep Quality Index Score > 5). Each patient slept 2 weeks with a Protac Ball Blanket® and 2 weeks with a control duvet. Randomisation defined the order of the 2-week sleep periods. Patients served as their own control in this design. The primary outcome was changes in total night-time sleep. Secondary outcomes were sleep-onset latency, number of awakenings, wake after sleep onset, daily use of pro necessitate sedatives and hypnotics, subjective sleep quality (Pittsburgh Sleep Quality Index), insomnia severity (Insomnia Severity Index), symptoms of depression (Hamilton Depression Rating Scale, Major Depression Inventory), symptoms of anxiety (Beck Anxiety Index), and patient-reported outcomes concerning interpersonal sensitivity, neurasthenia, anxiety and depression (Self-Reported Symptom State Scale). Paired two-sided t-tests were used to compare the means of the differences of the outcomes. Protac Ball Blanket® increased total night-time sleep by 12.9 min (95% confidence interval: 1.21–24.63, p = 0.031). Among the secondary outcomes, Protac Ball Blanket® decreased Hamilton Depression Rating Scale by 2.78 (95% confidence interval: −5.44; −0.11, p = 0.042) and Insomnia Severity Index by 2.98 (95% confidence interval: −5.45; −0.50, p = 0.020). No changes were observed in sleep-onset latency, number of awakenings, wake after sleep onset, Pittsburgh Sleep Quality Index, Major Depression Inventory, Beck Anxiety Index, Self-Reported Symptom State Scale, and medication use. The results suggest that some patients may benefit from Protac Ball Blanket® as an add-on non-pharmacological treatment to improve sleep in depression.

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Research Mon, 01 Jan 2024 23:03:34 +0100 108cee4c-f918-4872-9675-0d4252d36bd8
<![CDATA[Novelty-induced Consolidation of Hippocampus-Dependent Memories]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=00c85d04-effb-4fa1-8edf-a8f4e181178e&tx_pure_pure5%5BshowType%5D=pub&cHash=73372d8242397f0f8265ab8c74af93b5 Højgaard, K. Research Sun, 01 Jan 2023 23:03:34 +0100 00c85d04-effb-4fa1-8edf-a8f4e181178e <![CDATA[Dynamic multi-pinhole collimated brain SPECT of Parkinson’s disease by [<sup>123</sup>I]FP-CIT]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=c98c2ffb-4adb-4c6c-8c06-604318ac921e&tx_pure_pure5%5BshowType%5D=pub&cHash=5862548acfaa43d1456fd7939a29d886 Fredensborg, F. L.H., Thilsing-Hansen, K., Simonsen, J. A., et al. We investigated the feasibility of using a dopamine transporter (DaT) tracer ligand ([123I]FP-CIT) along with novel multi-pinhole brain collimators for dynamic brain single photon emission computed tomography (SPECT) in suspected Parkinson's disease patients. Thirteen patients underwent dynamic tracer acquisitions before standard imaging. Uptake values were corrected for partial volume effects. Specific binding ratio (SBRcalc) was calculated, reflecting binding potential relative to non-displaceable binding (BPND) in the cortex. Additional pharmacokinetic parameters (BPND, R1, k2) were estimated using the simplified reference tissue model, revealing differences between Kahraman low-score (LS) and high-score (HS) groups. Results showed increasing striatal tracer uptake until 100 min post-injection, with consistent values afterward. Uptake and SBRcalc ratios matched visual assessment. LS patients had lower putamen than caudate nucleus tracer uptake, decreased BPND values, while R1 and k2 values were comparable to HS patients. In conclusion, dynamic multi-pinhole SPECT using DaT tracer with the extraction of pharmacokinetic parameters is feasible and could help enable early differentiation of reduced and normal DaT values.

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Research Fri, 01 Mar 2024 23:03:34 +0100 c98c2ffb-4adb-4c6c-8c06-604318ac921e
<![CDATA[Repeated cannabidiol treatment affects neuroplasticity and endocannabinoid signaling in the prefrontal cortex of the Flinders Sensitive Line (FSL) rat model of depression.]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=eae99117-90d2-47d0-be41-da75bcc52ac6&tx_pure_pure5%5BshowType%5D=pub&cHash=c54fd68081107b8a3a23960cb5eba287 Domingos, L. B., Müller, H. K., da Silva, N. R., et al. Delayed therapeutic responses and limited efficacy are the main challenges of existing antidepressant drugs, thereby incentivizing the search for new potential treatments. Cannabidiol (CBD), non-psychotomimetic component of cannabis, has shown promising antidepressant effects in different rodent models, but its mechanism of action remains unclear. Herein, we investigated the antidepressant-like effects of repeated CBD treatment on behavior, neuroplasticity markers and lipidomic profile in the prefrontal cortex (PFC) of Flinders Sensitive Line (FSL), a genetic animal model of depression, and their control counterparts Flinders Resistant Line (FRL) rats. Male FSL animals were treated with CBD (10 mg/kg; i.p.) or vehicle (7 days) followed by Open Field Test (OFT) and the Forced Swimming Test (FST). The PFC was analyzed by a) western blotting to assess markers of synaptic plasticity and cannabinoid signaling in synaptosome and cytosolic fractions; b) mass spectrometry-based lipidomics to investigate endocannabinoid levels (eCB). CBD attenuated the increased immobility observed in FSL, compared to FRL in FST, without changing the locomotor behavior in the OFT. In synaptosomes, CBD increased ERK1, mGluR5, and Synaptophysin, but failed to reverse the reduced CB1 and CB2 levels in FSL rats. In the cytosolic fraction, CBD increased ERK2 and decreased mGluR5 expression in FSL rats. Surprisingly, there were no significant changes in eCB levels in response to CBD treatment. These findings suggest that CBD effects in FSL animals are associated with changes in synaptic plasticity markers involving mGluR5, ERK1, ERK2, and synaptophysin signaling in the PFC, without increasing the levels of endocannabinoids in this brain region.

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Research Wed, 01 May 2024 23:03:34 +0200 eae99117-90d2-47d0-be41-da75bcc52ac6
<![CDATA[Sildenafil, alone and in combination with imipramine or escitalopram, display antidepressant-like effects in an adrenocorticotropic hormone-induced (ACTH) rodent model of treatment-resistant depression]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=a385936c-1909-4593-9cb2-3147667fb4dd&tx_pure_pure5%5BshowType%5D=pub&cHash=43c4ae9779a86e2678671edcd08fd991 Bernardus Saayman, J. L., Harvey, B. H., Wegener, G., Brink, C. B. Background: Major depressive disorder (MDD) represents a challenge with high prevalence and limited effectiveness of existing treatments, particularly in cases of treatment-resistant depression (TRD). Innovative strategies and alternative drug targets are therefore necessary. Sildenafil, a selective phosphodiesterase type 5 (PDE5) inhibitor, is known to exert neuroplastic, anti-inflammatory, and antioxidant properties, and is a promising antidepressant drug candidate. Aim: To investigate whether sildenafil monotherapy or in combination with a known antidepressant, can elicit antidepressant-like effects in an adrenocorticotropic hormone (ACTH)-induced rodent model of TRD. Methods: ACTH-naïve and ACTH-treated male Sprague-Dawley (SD) rats received various sub-acute drug treatments, followed by behavioural tests and biochemical analyses conversant with antidepressant actions. Results: Sub-chronic ACTH treatment induced significant depressive-like behaviour in rats, evidenced by increased immobility during the forced swim test (FST). Sub-acute sildenafil (10 mg/kg) (SIL-10) (but not SIL-3), and combinations of imipramine (15 mg/kg) (IMI-15) and sildenafil (3 mg/kg) (SIL-3) or escitalopram (15 mg/kg) (ESC-15) and SIL-3, exhibited significant antidepressant-like effects. ACTH treatment significantly elevated hippocampal levels of brain-derived neurotrophic factor (BDNF), serotonin, norepinephrine, kynurenic acid (KYNUA), quinolinic acid (QUINA), and glutathione. The various mono- and combined treatments significantly reversed some of these changes, whereas IMI-15 + SIL-10 significantly increased glutathione disulfide levels. ESC-15 + SIL-3 significantly reduced plasma corticosterone levels. Conclusion: This study suggests that sildenafil shows promise as a treatment for TRD, either as a stand-alone therapy or in combination with a traditional antidepressant. The neurobiological mechanism underlying the antidepressant-like effects of the different sildenafil mono- and combination therapies reflects a multimodal action and cannot be explained in full by changes in the individually measured biomarker levels.

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Research Mon, 01 Apr 2024 23:03:34 +0200 a385936c-1909-4593-9cb2-3147667fb4dd
<![CDATA[Unravelling the complex tapestry of addiction]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=fa147f8e-9811-47a7-b48f-a23ee44f470c&tx_pure_pure5%5BshowType%5D=pub&cHash=3ebf69b4b5538c4d21c963251fedd2c6 Wegener, G. Research Mon, 01 Apr 2024 23:03:34 +0200 fa147f8e-9811-47a7-b48f-a23ee44f470c <![CDATA[Mutation in the TRKB Cholesterol Recognition Site that blocks Antidepressant Binding does not Influence the Basal or BDNF-Stimulated Activation of TRKB]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=0e46f887-c8d3-4d69-b5d7-d6fe476dc9b3&tx_pure_pure5%5BshowType%5D=pub&cHash=0e987d2c1eb586708b096f79177402c2 Biojone, C., Cannarozzo, C., Seiffert, N., et al. Brain-derived neurotrophic factor (BDNF) acting upon its receptor Neurotrophic tyrosine kinase receptor 2 (NTRK2, TRKB) plays a central role in the development and maintenance of synaptic function and activity- or drug-induced plasticity. TRKB possesses an inverted cholesterol recognition and alignment consensus sequence (CARC), suggesting this receptor can act as a cholesterol sensor. We have recently shown that antidepressant drugs directly bind to the CARC domain of TRKB dimers, and that this binding as well as biochemical and behavioral responses to antidepressants are lost with a mutation in the TRKB CARC motif (Tyr433Phe). However, it is not clear if this mutation can also compromise the receptor function and lead to behavioral alterations. Here, we observed that Tyr433Phe mutation does not alter BDNF binding to TRKB, or BDNF-induced dimerization of TRKB. In this line, primary cultures from embryos of heterozygous Tyr433Phe mutant mice (hTRKB.Tyr433Phe) are responsive to BDNF-induced activation of TRKB, and samples from adult mice do not show any difference on TRKB activation compared to wild-type littermates (TRKB.wt). The behavioral phenotype of hTRKB.Tyr433Phe mice is indistinguishable from the wild-type mice in cued fear conditioning, contextual discrimination task, or the elevated plus maze, whereas mice heterozygous to BDNF null allele show a phenotype in context discrimination task. Taken together, our results indicate that Tyr433Phe mutation in the TRKB CARC motif does not show signs of loss-of-function of BDNF responses, while antidepressant binding to TRKB and responses to antidepressants are lost in Tyr433Phe mutants, making them an interesting mouse model for antidepressant research.

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Research Sun, 01 Dec 2024 23:03:34 +0100 0e46f887-c8d3-4d69-b5d7-d6fe476dc9b3
<![CDATA[Long-term impact of maternal obesity on the gliovascular unit and ephrin signaling in the hippocampus of adult offspring]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=f97a17a6-f73c-4ef8-ad95-d70f28b75b9d&tx_pure_pure5%5BshowType%5D=pub&cHash=64a2f1b23a7c1551123ecf90db758ee5 Shiadeh, S. M. J., Goretta, F., Svedin, P., Jansson, T., Mallard, C., Ardalan, M. Background: Children born to obese mothers are at increased risk of developing mood disorders and cognitive impairment. Experimental studies have reported structural changes in the brain such as the gliovascular unit as well as activation of neuroinflammatory cells as a part of neuroinflammation processing in aged offspring of obese mothers. However, the molecular mechanisms linking maternal obesity to poor neurodevelopmental outcomes are not well established. The ephrin system plays a major role in a variety of cellular processes including cell–cell interaction, synaptic plasticity, and long-term potentiation. Therefore, in this study we determined the impact of maternal obesity in pregnancy on cortical, hippocampal development, vasculature and ephrin-A3/EphA4-signaling, in the adult offspring in mice. Methods: Maternal obesity was induced in mice by a high fat/high sugar Western type of diet (HF/HS). We collected brain tissue (prefrontal cortex and hippocampus) from 6-month-old offspring of obese and lean (control) dams. Hippocampal volume, cortical thickness, myelination of white matter, density of astrocytes and microglia in relation to their activity were analyzed using 3-D stereological quantification. mRNA expression of ephrin-A3, EphA4 and synaptic markers were measured by qPCR in the brain tissue. Moreover, expression of gap junction protein connexin-43, lipocalin-2, and vascular CD31/Aquaporin 4 were determined in the hippocampus by immunohistochemistry. Results: Volume of hippocampus and cortical thickness were significantly smaller, and myelination impaired, while mRNA levels of hippocampal EphA4 and post-synaptic density (PSD) 95 were significantly lower in the hippocampus in the offspring of obese dams as compared to offspring of controls. Further analysis of the hippocampal gliovascular unit indicated higher coverage of capillaries by astrocytic end-feet, expression of connexin-43 and lipocalin-2 in endothelial cells in the offspring of obese dams. In addition, offspring of obese dams demonstrated activation of microglia together with higher density of cells, while astrocyte cell density was lower. Conclusion: Maternal obesity affects brain size, impairs myelination, disrupts the hippocampal gliovascular unit and decreases the mRNA expression of EphA4 and PSD-95 in the hippocampus of adult offspring. These results indicate that the vasculature–glia cross-talk may be an important mediator of altered synaptic plasticity, which could be a link between maternal obesity and neurodevelopmental/neuropsychiatric disorders in the offspring. Graphical Abstract: (Figure presented.).

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Research Thu, 01 Feb 2024 23:03:34 +0100 f97a17a6-f73c-4ef8-ad95-d70f28b75b9d
<![CDATA[The arterial blood sampling associated with PET imaging studies can lead to post-scan complications in Göttingen minipigs]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=c9dcf4e9-33cd-497a-8ead-f77d4e374913&tx_pure_pure5%5BshowType%5D=pub&cHash=0ea52ea6facacc94e8515d4c2b7df10b Alstrup, A. K. O., Lillethorup, T. P., Landau, A., Afzelius, P. Research Tue, 21 May 2024 23:03:34 +0200 c9dcf4e9-33cd-497a-8ead-f77d4e374913 <![CDATA[Automated behavioral phenotyping of ouabain-treated flinders sensitive line rats: toward an animal model for the mixed state?]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=415c61c9-a044-45bf-9656-b0fe18e33304&tx_pure_pure5%5BshowType%5D=pub&cHash=6a5ce6793b3d931c5f0352c80fa54219 Arjmand, S., Andreatini, R., Wegener, G. Research Sun, 01 Jan 2023 23:03:34 +0100 415c61c9-a044-45bf-9656-b0fe18e33304 <![CDATA[An acute thrombus formation in the left coronary artery of an atypical Kawasaki patient]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=b4efeee1-e376-49db-998a-97d8ea04bb7a&tx_pure_pure5%5BshowType%5D=pub&cHash=484f01fd4c9108b9b28c1f4c35738111 Bagheri, M. M., Arjmand, S., Torabinejad, M. H., Behzadi, M.

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Research Mon, 01 Jan 2018 23:03:34 +0100 b4efeee1-e376-49db-998a-97d8ea04bb7a
<![CDATA[Evaluation and awareness of over the counter use of non-steroidal anti-inflammatory drugs]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=c477787e-a2fb-47ff-806a-014a8f5cec8a&tx_pure_pure5%5BshowType%5D=pub&cHash=7edc02230939653336a48bc707f7f75f Amirimoghadam, P., Zihayat, B., Dabaghzadeh, F., et al.

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Research Wed, 01 Mar 2017 23:03:34 +0100 c477787e-a2fb-47ff-806a-014a8f5cec8a
<![CDATA[Attenuation Effect of Cannabinoid Type 1 Receptor Activation on Methamphetamine-Induced Neurodegeneration and Locomotion Impairments among Male Rats]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=03b331ca-5924-4d3f-b784-c1bd48cbd305&tx_pure_pure5%5BshowType%5D=pub&cHash=60bf47dd2d5f23cd310ef27a4860a03f Ramshini, E., Dabiri, S., Arjmand, S., et al. Research Sun, 01 Jan 2017 23:03:34 +0100 03b331ca-5924-4d3f-b784-c1bd48cbd305 <![CDATA[Bipolar disorder and the endocannabinoid system]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=320a7a41-257d-4662-9dc7-a3fab36cc784&tx_pure_pure5%5BshowType%5D=pub&cHash=6fcb3f8c555d7b90d4d1ed2b84c4a3f2 Arjmand, S., Behzadi, M., Kohlmeier, K. A., Mazhari, S., Sabahi, A., Shabani, M. OBJECTIVE: Bipolar disorder (BD) is a debilitating, lifelong neuropsychiatric illness characterised by unsteady mood states which vacillate from (hypo)mania to depression. Despite the availability of pharmaceutical agents which can be effective in ameliorating the acute affective symptoms and prevent episodic relapse, BD is inadequately treated in a subset of patients. The endocannabinoid system (ECS) is known to exert neuromodulatory effects on other neurotransmitter systems critical in governing emotions. Several studies ranging from clinical to molecular, as well as anecdotal evidence, have placed a spotlight on the potential role of the ECS in the pathophysiology of BD. In this perspective, we present advantages and disadvantages of cannabis use in the management of illness course of BD and provide mechanistic insights into how this system might contribute to the pathophysiology of BD.

RESULTS: We highlight the putative role of selective cannabinoid receptor 2 (CB2) agonists in BD and briefly discuss findings which provide a rationale for targeting the ECS to assuage the symptoms of BD. Further, data encourage basic and clinical studies to determine how cannabis and cannabinoids (CBs) can affect mood and to investigate emerging CB-based options as probable treatment approaches.

CONCLUSION: The probable role of the ECS has been almost neglected in BD; however, from data available which suggest a role of ECS in mood control, it is justified to support conducting comprehensive studies to determine whether ECS manipulation could positively affect BD. Based on the limited available data, we suggest that activation of CB2 may stabilise mood in this disorder.

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Research Thu, 01 Aug 2019 23:03:34 +0200 320a7a41-257d-4662-9dc7-a3fab36cc784
<![CDATA[Comparing Copper Serum Level and Cognitive Functioning in Patients With Schizophrenia and Healthy Controls]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=d628f382-8fec-4bdf-aab9-7ef9161505d7&tx_pure_pure5%5BshowType%5D=pub&cHash=5a380199a917487de15bac0763efb059 Mazhari, S., Arjmand, S., Eslami Shahrbabaki, M., Karimi Ghoughari, E.

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Research Wed, 01 Jan 2020 23:03:34 +0100 d628f382-8fec-4bdf-aab9-7ef9161505d7
<![CDATA[Cannabinoids and Tremor Induced by Motor-related Disorders: Friend or Foe?]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=6db05bc4-538a-467e-96a7-dd573834440f&tx_pure_pure5%5BshowType%5D=pub&cHash=ea64acde28fc8f2edd57c4d94423035b Arjmand, S., Vaziri, Z., Behzadi, M., Abbassian, H., Stephens, G. J., Shabani, M. Research Thu, 01 Oct 2015 23:03:34 +0200 6db05bc4-538a-467e-96a7-dd573834440f <![CDATA[Contribution of CB1Rs in anxiety-related behaviors but not locomotor deficits induced by methamphetamine]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=0647b132-7ca1-4cec-8159-6a614c179c0b&tx_pure_pure5%5BshowType%5D=pub&cHash=fdd68f55d03c8170291d36acc2327c4d Ramshini, E., Sepehri, G., Ahmadi-Zeidabadi, M., Arjmand, S., Khaksari, M., Shabani, M. Research Thu, 01 Feb 2018 23:03:34 +0100 0647b132-7ca1-4cec-8159-6a614c179c0b <![CDATA[Modulation of sphingosine-1-phosphate receptor ameliorates harmaline-induced essential tremor in rat]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=f52aedc2-46ea-4df0-9f8f-afc93debc88a&tx_pure_pure5%5BshowType%5D=pub&cHash=2f718b01ecf032ae298f61514644e071 Dahmardeh, N., Asadi-Shekaari, M., Arjmand, S., Kalantaripour, T., Basiri, M., Shabani, M. Research Sat, 01 Jul 2017 23:03:34 +0200 f52aedc2-46ea-4df0-9f8f-afc93debc88a <![CDATA[Nitric oxide pathway presumably does not contribute to antianxiety and memory retrieval effects of losartan]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=7fd7ebec-54a4-4955-827e-d9a380527e54&tx_pure_pure5%5BshowType%5D=pub&cHash=3821b9c1016dfb26b277fca7bf0e6450 Aghaei, I., Arjmand, S., Yousefzadeh Chabok, S., Tondar, M., Shabani, M. Research Fri, 01 Sep 2017 23:03:34 +0200 7fd7ebec-54a4-4955-827e-d9a380527e54 <![CDATA[A Brain on a Roller Coaster: Can the Dopamine Reward System Act as a Protagonist to Subdue the Ups and Downs of Bipolar Disorder?]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=c4046f69-8ecf-4875-8bd1-85a2e57e056b&tx_pure_pure5%5BshowType%5D=pub&cHash=592a999799e302a15c2ef74ca6b535cd Arjmand, S., Behzadi, M., Stephens, G. J., et al. Research Thu, 01 Jun 2017 23:03:34 +0200 c4046f69-8ecf-4875-8bd1-85a2e57e056b <![CDATA[A road to bring Brij52 back to attention: Shear stress sensitive Brij52 niosomal carriers for targeted drug delivery to obstructed blood vessels]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=fadd2c26-4f7c-4b24-8ab5-a56b453aeabb&tx_pure_pure5%5BshowType%5D=pub&cHash=b8b54c77f2187821b6b12691cc983988 Arjmand, S., Pardakhty, A., Forootanfar, H., Khazaeli, P. Research Sat, 01 Dec 2018 23:03:34 +0100 fadd2c26-4f7c-4b24-8ab5-a56b453aeabb <![CDATA[Role of anxiety and depression in association with migraine and myofascial pain temporomandibular disorder]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=dd5ed20b-9d04-4b91-8d98-ab35757ccf62&tx_pure_pure5%5BshowType%5D=pub&cHash=61f901a7a9c68c1d2084c17a2308ffee Shabani, M., Nazeri, M., Ghahrechahi, H., et al. Research Mon, 01 Jan 2018 23:03:34 +0100 dd5ed20b-9d04-4b91-8d98-ab35757ccf62 <![CDATA[Laccase-Mediated Treatment of Pharmaceutical Wastes]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=232dc9ae-cf06-4b47-bd1d-4ec17a86e392&tx_pure_pure5%5BshowType%5D=pub&cHash=b243a1c15b7e6f2f5ee3bdef60dd64cf Forootanfar, H., Arjmand, S., Behzadi, M., Faramarzi, M. A. Research Mon, 01 Jan 2018 23:03:34 +0100 232dc9ae-cf06-4b47-bd1d-4ec17a86e392 <![CDATA[Validity and reliability of a Persian version of the Dissociative Experiences Scale II (DES-II) on Iranian patients diagnosed with schizophrenia and mood disorders]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=daecd52b-434f-4ae7-a050-9593e2bcce13&tx_pure_pure5%5BshowType%5D=pub&cHash=cee8c66bf9a5d3876d878e6f3c39a3c7 Ghaffarinejad, A., Sattari, N., Raaii, F., Arjmand, S. Research Tue, 01 Oct 2019 23:03:34 +0200 daecd52b-434f-4ae7-a050-9593e2bcce13 <![CDATA[When Thoughts Are in a Race: Area 10 and Bipolar Disorders]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=e1c9332b-a1b7-4bd4-a8fc-2aada6afe650&tx_pure_pure5%5BshowType%5D=pub&cHash=8ff84d92aa0b5092a524b944f791622c Arjmand, S., Sabahi, A., Sheibani, V. Research Tue, 01 Oct 2019 23:03:34 +0200 e1c9332b-a1b7-4bd4-a8fc-2aada6afe650 <![CDATA[Looking into a Deluded Brain through a Neuroimaging Lens]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=b80722cc-9629-4f06-96ae-83019394f8e4&tx_pure_pure5%5BshowType%5D=pub&cHash=7d7fb8165c8610a7d865bf966486c43f Arjmand, S., Kohlmeier, K. A., Behzadi, M., Ilaghi, M., Mazhari, S., Shabani, M. Delusions are irrational, tenacious, and incorrigible false beliefs that are the most common symptom of a range of brain disorders including schizophrenia, Alzheimer’s, and Parkinson’s disease. In the case of schizophrenia and other primary delusional disorders, their appearance is often how the disorder is first detected and can be sufficient for diagnosis. At this time, not much is known about the brain dysfunctions leading to delusions, and hindering our understanding is that the complexity of the nature of delusions, and their very unique relevance to the human experience has hampered elucidation of their underlying neurobiology using either patients or animal models. Advances in neuroimaging along with improved psychiatric and cognitive modeling offers us a new opportunity to look with more investigative power into the deluded brain. In this article, based on data obtained from neuroimaging studies, we have attempted to draw a picture of the neural networks involved when delusion is present and evaluate whether different manifestations of delusions engage different regions of the brain.

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Research Wed, 01 Jul 2020 23:03:34 +0200 b80722cc-9629-4f06-96ae-83019394f8e4
<![CDATA[Prenatal cocaine exposure and its influence on pediatric epigenetic clocks and epigenetic scores in humans]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=69499261-a5b7-4cf5-a4db-361e1586a262&tx_pure_pure5%5BshowType%5D=pub&cHash=d6247ed011de3d99ebfa48d42ba1148b Viola, T. W., Danzer, C., Mardini, V., et al. The investigation of the effects of prenatal cocaine exposure (PCE) on offspring has been inconsistent, with few studies investigating biological outcomes in humans. We profiled genome-wide DNA methylation (DNAm) of umbilical cord blood (UCB) from newborns with (n = 35) and without (n = 47) PCE. We used DNAm data to (1) assess pediatric epigenetic clocks at birth and (2) to estimate epigenetic scores (ES) for lifetime disorders. We generated gestational epigenetic age estimates (DNAmGA) based on Knight and Bohlin epigenetic clocks. We also investigated the association between DNAmGA and UCB serum brain-derived neurotrophic factor (BDNF) levels. Considering the large-scale DNAm data availability and existing evidence regarding PCE as a risk for health problems later in life, we generated ES for tobacco smoking, psychosis, autism, diabetes, and obesity. A gene ontology (GO) analysis on the CpGs included in the ES with group differences was performed. PCE was associated with lower DNAmGA in newborns, and this effect remained significant when controlling for potential confounders, such as blood cell type composition predicted by DNAm and obstetric data. DNAmGA was negatively correlated with BDNF levels in the serum of UCB. Higher tobacco smoking, psychosis, and diabetes ES were found in the PCE group. The GO analysis revealed GABAergic synapses as a potential pathway altered by PCE. Our findings of decelerated DNAmGA and ES for adverse phenotypes associated with PCE, suggest that the effects of gestational cocaine exposure on the epigenetic landscape of human newborns are detectable at birth.

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Research Mon, 01 Jan 2024 23:03:34 +0100 69499261-a5b7-4cf5-a4db-361e1586a262
<![CDATA[From hormones to behavior through microglial mitochondrial function]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=6e9a36ad-aa90-48db-8e36-cd59972799ba&tx_pure_pure5%5BshowType%5D=pub&cHash=bbd5c55a6da070b79005a26f1677b17e Ardalan, M., Mallard, C. Research Fri, 01 Mar 2024 23:03:34 +0100 6e9a36ad-aa90-48db-8e36-cd59972799ba <![CDATA[A molecular perspective on mGluR5 regulation in the antidepressant effect of ketamine]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=48747c5d-eadd-4297-9ec7-53420a97be22&tx_pure_pure5%5BshowType%5D=pub&cHash=7e8d68d173b56e377122b335de095fd1 Elmeseiny, O. S. A., Müller, H. K. Ketamine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, has received much attention for its rapid antidepressant effects. A single administration of ketamine elicits rapid and sustained antidepressant effects in both humans and animals. Current efforts are focused on uncovering molecular mechanisms responsible for ketamine's antidepressant activity. Ketamine primarily acts via the glutamatergic pathway, and increasing evidence suggests that ketamine induces synaptic and structural plasticity through increased translation and release of neurotrophic factors, activation of mammalian target of rapamycin (mTOR), and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR)-mediated synaptic potentiation. However, the initial events triggering activation of intracellular signaling cascades and the mechanisms responsible for the sustained antidepressant effects of ketamine remain poorly understood. Over the last few years, it has become apparent that in addition to the fast actions of the ligand-gated AMPARs and NMDARs, metabotropic glutamate receptors (mGluRs), and particularly mGluR5, may also play a role in the antidepressant action of ketamine. Although research on mGluR5 in relation to the beneficial actions of ketamine is still in its infancy, a careful evaluation of the existing literature can identify converging trends and provide new interpretations. Here, we review the current literature on mGluR5 regulation in response to ketamine from a molecular perspective and propose a possible mechanism linking NMDAR inhibition to mGluR5 modulation.

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Research Thu, 01 Feb 2024 23:03:34 +0100 48747c5d-eadd-4297-9ec7-53420a97be22
<![CDATA[Involvement of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the antidepressant-like effect and in the stress response]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=49cc2008-814d-407b-abaf-931028971226&tx_pure_pure5%5BshowType%5D=pub&cHash=1263e650938f94ccc7ac1c6a034066f3 Moura Silveira, K. Research Sun, 01 Oct 2023 23:03:34 +0200 49cc2008-814d-407b-abaf-931028971226 <![CDATA[Translational Imaging of Synaptic Dysfunction in Mental Health Disorders]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=a3dc46d1-d091-4b4c-bbf6-4e0b57f13486&tx_pure_pure5%5BshowType%5D=pub&cHash=28d3a1a9e16c7f647fb74a0051cbe1c6 Bærentzen, S. L. Research Mon, 01 Jan 2024 23:03:34 +0100 a3dc46d1-d091-4b4c-bbf6-4e0b57f13486 <![CDATA[Rhesus monkeys exhibiting spontaneous ritualistic behaviors resembling obsessive-compulsive disorder]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=552850c8-79c6-4570-8d28-60d23bcafcc9&tx_pure_pure5%5BshowType%5D=pub&cHash=6c34a504ab08b9344abff49ab35094b9 Zhai, R., Tong, G., Li, Z., et al. Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric disorder that affects ∼2%-3% of the population globally. Studying spontaneous OCD-like behaviors in non-human primates may improve our understanding of the disorder. In large rhesus monkey colonies, we found 10 monkeys spontaneously exhibiting persistent sequential motor behaviors (SMBs) in individual-specific sequences that were repetitive, time-consuming and stable over prolonged periods. Genetic analysis revealed severely damaging mutations in genes associated with OCD risk in humans. Brain imaging showed that monkeys with SMBs had larger gray matter (GM) volumes in the left caudate nucleus and lower fractional anisotropy of the corpus callosum. The GM volume of the left caudate nucleus correlated positively with the daily duration of SMBs. Notably, exposure to a stressor (human presence) significantly increased SMBs. In addition, fluoxetine, a serotonergic medication commonly used for OCD, decreased SMBs in these monkeys. These findings provide a novel foundation for developing better understanding and treatment of OCD.

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Research Wed, 01 Nov 2023 23:03:34 +0100 552850c8-79c6-4570-8d28-60d23bcafcc9
<![CDATA[Putative effects of cannabidiol in depression and synaptic plasticity]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=d2debb85-7241-4877-83a3-ddcdc55dfcb9&tx_pure_pure5%5BshowType%5D=pub&cHash=1a8d3659715bc8bcc522a2e282da3c78 Joca, S., Silote, G. P., Sartim, A., Sales, A., Guimarães, F., Wegener, G. Significant limitations with the currently available antidepressant treatment strategies have inspired research on finding new and more efficient drugs to treat depression. Cannabidiol (CBD) is a nonpsychotomimetic component of Cannabis sativa and preclinical evidence suggests it can be a promising new antidepressant. The first evidence on CBD antidepressive properties was shown 10 years ago and it has been confirmed by several other groups since then. More recent studies have shown that CBD promotes rapid and sustained antidepressant effect in different animal models. Such effects seem to involve increased brain-derived neurotrophic factor (BDNF) signaling in limbic brain regions important for stress adaptation and depression neurobiology, resulting in increased synaptogenesis and neurogenesis. CBD has a complex pharmacology, with the ability to interact with multiple neurotransmitter systems involved in depression, including the serotonergic, glutamatergic, and endocannabinoid systems. It is not yet clear how these mechanisms are integrated to promote the molecular and behavioral effects induced by CBD. Despite evidence from animal studies, there is currently insufficient evidence from human studies to support that CBD could promote mood-improving effects in depressed patients. Nevertheless, this chapter reviews and discusses the current evidence and highlights the need for more investigation on the putative antidepressant effect induced by CBD.

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Research Fri, 01 Jan 2021 23:03:34 +0100 d2debb85-7241-4877-83a3-ddcdc55dfcb9
<![CDATA[Proteomics identifies lipocalin-2 in neonatal inflammation associated with cerebrovascular alteration in mice and preterm infants]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=67dfd4a5-79d8-4a56-8646-c335f55514b6&tx_pure_pure5%5BshowType%5D=pub&cHash=92f27101cc16739380d8419085011c97 Gravina, G., Ardalan, M., Chumak, T., et al. Staphylococcus (S.) epidermidis is the most common nosocomial coagulase-negative staphylococci infection in preterm infants. Clinical signs of infection are often unspecific and novel markers to complement diagnosis are needed. We investigated proteomic alterations in mouse brain after S. epidermidis infection and in preterm infant blood. We identified lipocalin-2 (LCN2) as a crucial protein associated with cerebrovascular changes and astrocyte reactivity in mice. We further proved that LCN2 protein expression was associated with endothelial cells but not astrocyte reactivity. By combining network analysis and differential expression approaches, we identified LCN2 linked to blood C-reactive protein levels in preterm infants born <28 weeks of gestation. Blood LCN2 levels were associated with similar alterations of cytokines and chemokines in both infected mice and human preterm infants with increased levels of C-reactive protein. This experimental and clinical study suggests that LCN2 may be a marker of preterm infection/inflammation associated with cerebrovascular changes and neuroinflammation.

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Research Sat, 01 Jul 2023 23:03:34 +0200 67dfd4a5-79d8-4a56-8646-c335f55514b6
<![CDATA[In Ischemic Heart Disease, Reduced Sensitivity to Pressure at the Sternum Accompanies Lower Mortality after Five Years]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=cca13291-5942-4cb8-89a5-160de738bfff&tx_pure_pure5%5BshowType%5D=pub&cHash=21e0de44870bef2246b22ea30350f2e5 Ballegaard, S., Faber, J., Selmer, C., et al. Background: Autonomic nervous system dysfunction (ANSD) is associated with negative prognosis of ischemic heart disease (IHD). Elevated periosteal pressure sensitivity (PPS) at the sternum relates to ANSD and sympathetic hyperactivity. Two previous observational case–control studies of the effect of reduction of PPS suggested lower all-cause mortality from IHD and stroke. We now used a specific daily, adjunct, non-pharmacological program of reduction of elevated PPS to test the hypothetical association between the intervention and reduced all-cause mortality in patients with stable IHD in a randomized controlled trial (RCT). Methods: We completed active (n = 106) and passive interventions (n = 107) and compared the five-year mortalities. We also compared the five-year individual all-cause mortality of each participant to approximately 35.000 members of the general population of Denmark. Pooling the mortality data from the active group of the RCT with the two preliminary studies, we registered the mortality following active intervention of 1.168 person-years, compared to 40 million person-years of the pooled general population. Results: We recorded fewer deaths of the active RCT intervention group than of the corresponding control group from the general population (p = 0.01), as well as of the passive RCT intervention group (p = 0.035). The meta-analysis of the three studies together demonstrated reduced 4.2-year all-cause mortality of 60% (p = 0.007). Conclusions: The test of the hypothetical effect of an intervention aimed at the attenuation of ANSD accompanied by a lowered PPS revealed reduced all-cause mortality in patients with stable IHD.

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Research Fri, 01 Dec 2023 23:03:34 +0100 cca13291-5942-4cb8-89a5-160de738bfff
<![CDATA[Neuron-specific gene NSG1 binds to and positively regulates sortilin ectodomain shedding via a metalloproteinase-dependent mechanism]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=f5fc04d2-eab2-4893-8154-259cb1567eae&tx_pure_pure5%5BshowType%5D=pub&cHash=98235c04acdae0e5ca151e500db178a4 Overby, M., Serrano-Rodriguez, A., Dadras, S., et al. Increasing evidence suggests that aberrant regulation of sortilin ectodomain shedding can contribute to amyloid-β pathology and frontotemporal dementia, although the mechanism by which this occurs has not been elucidated. Here, we probed for novel binding partners of sortilin using multiple and complementary approaches and identified two proteins of the neuron-specific gene (NSG) family, NSG1 and NSG2, that physically interact and colocalize with sortilin. We show both NSG1 and NSG2 induce subcellular redistribution of sortilin to NSG1- and NSG2-enriched compartments. However, using cell surface biotinylation, we found only NSG1 reduced sortilin cell surface expression, which caused significant reductions in uptake of progranulin, a molecular determinant for frontotemporal dementia. In contrast, we demonstrate NSG2 has no effect on sortilin cell surface abundance or progranulin uptake, suggesting specificity for NSG1 in the regulation of sortilin cell surface expression. Using metalloproteinase inhibitors and A disintegrin and metalloproteinase 10 KO cells, we further show that NSG1-dependent reduction of cell surface sortilin occurred via proteolytic processing by A disintegrin and metalloproteinase 10 with a concomitant increase in shedding of sortilin ectodomain to the extracellular space. This represents a novel regulatory mechanism for sortilin ectodomain shedding that is regulated in a neuron-specific manner. Furthermore, this finding has implications for the development of strategies for brain-specific regulation of sortilin and possibly sortilin-driven pathologies.

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Research Fri, 01 Dec 2023 23:03:34 +0100 f5fc04d2-eab2-4893-8154-259cb1567eae
<![CDATA[From microRNA to protein, linking the neurotrophic hypothesis of depression to the Wistar Kyoto rat]]> https://tnu.au.dk/publications/all-publications?tx_pure_pure5%5Baction%5D=single&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Bid%5D=bb41c739-9fdb-4d80-b234-bee0bbb57d29&tx_pure_pure5%5BshowType%5D=pub&cHash=3c655021141e0c583f5c0912e143e1e9 Kaadt, E., Hedemann, N., Damgaard, C. K., Müller, H. K., Elfving, B. Research Sun, 01 Jan 2023 23:03:34 +0100 bb41c739-9fdb-4d80-b234-bee0bbb57d29