Biological psychiatry global open science最新文献

{"title":"Pharmacological Enhancement of Adult Hippocampal Neurogenesis Improves Behavioral Pattern Separation in Young and Aged Male Mice","authors":"Wei-li Chang ,&nbsp;Karly Tegang ,&nbsp;Benjamin A. Samuels ,&nbsp;Michael Saxe ,&nbsp;Juergen Wichmann ,&nbsp;Denis J. David ,&nbsp;Indira Mendez David ,&nbsp;Angélique Augustin ,&nbsp;Holger Fischer ,&nbsp;Sabrina Golling ,&nbsp;Jens Lamerz ,&nbsp;Doris Roth ,&nbsp;Martin Graf ,&nbsp;Sannah Zoffmann ,&nbsp;Luca Santarelli ,&nbsp;Ravi Jagasia ,&nbsp;René Hen","doi":"10.1016/j.bpsgos.2024.100419","DOIUrl":"10.1016/j.bpsgos.2024.100419","url":null,"abstract":"<div><h3>Background</h3><div>Impairments in behavioral pattern separation (BPS)—the ability to distinguish between similar contexts or experiences—contribute to memory interference and overgeneralization seen in many neuropsychiatric conditions, including depression, anxiety, posttraumatic stress disorder, dementia, and age-related cognitive decline. Although BPS relies on the dentate gyrus and is sensitive to changes in adult hippocampal neurogenesis, its significance as a pharmacological target has not been tested.</div></div><div><h3>Methods</h3><div>In this study, we applied a human neural stem cell high-throughput screening cascade to identify compounds that increase human neurogenesis. One compound with a favorable profile, RO6871135, was then tested in young and aged mice for effects on BPS and anxiety-related behaviors.</div></div><div><h3>Results</h3><div>Chronic treatment with RO6871135 (7.5 mg/kg) increased adult hippocampal neurogenesis and improved BPS in a fear discrimination task in both young and aged mice. RO6871135 treatment also lowered innate anxiety-like behavior, which was more apparent in mice exposed to chronic corticosterone. Ablation of adult hippocampal neurogenesis by hippocampal irradiation supported a neurogenesis-dependent mechanism for RO6871135-induced improvements in BPS. To identify possible mechanisms of action, in vitro and in vivo kinase inhibition and chemical proteomics assays were performed. These tests indicated that RO6871135 inhibited CDK8, CDK11, CaMKIIa, CaMKIIb, MAP2K6, and GSK-3β. An analog compound also demonstrated high affinity for CDK8, CaMKIIa, and GSK-3β.</div></div><div><h3>Conclusions</h3><div>These studies demonstrate a method for empirical identification and preclinical testing of novel neurogenic compounds that can improve BPS and point to possible novel mechanisms that can be interrogated for the development of new therapies to improve specific endophenotypes such as impaired BPS.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 2","pages":"Article 100419"},"PeriodicalIF":4.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERK2 Signaling in the Nucleus Accumbens Facilitates Stress Susceptibility and Cocaine Reinstatement","authors":"Lyonna F. Parise ,&nbsp;Sergio D. Iñiguez ,&nbsp;Brandon L. Warren ,&nbsp;Eric M. Parise ,&nbsp;Ryan K. Bachtell ,&nbsp;David M. Dietz ,&nbsp;Eric J. Nestler ,&nbsp;Carlos A. Bolaños-Guzmán","doi":"10.1016/j.bpsgos.2024.100416","DOIUrl":"10.1016/j.bpsgos.2024.100416","url":null,"abstract":"<div><h3>Background</h3><div>Second-messenger signaling within the mesolimbic reward circuit plays a key role in the negative effects of stress and the underlying mechanisms that promote drug abuse. Because the nucleus accumbens (NAc) integrates reward valence, we investigated how ERK2 (extracellular signal-regulated protein kinase-2) signaling affects the development of stress-related comorbidities, including negative affect and drug sensitivity.</div></div><div><h3>Methods</h3><div>We assessed how chronic unpredictable stress influenced the phosphorylation of ERK2-signaling proteins within the NAc of male Sprague Dawley rats. Using a herpes simplex virus, we either upregulated or downregulated NAc ERK2 activation and evaluated behavioral responses to stress-eliciting stimuli (elevated plus maze, open field, forced swim test) and cocaine-seeking behavior (conditioned place preference, self-administration). We also examined ERK2-mediated modifications in spine morphology of medium spiny neurons within the NAc.</div></div><div><h3>Results</h3><div>Chronic unpredictable stress increased the phosphorylation of ERK2-signaling proteins within the NAc. Viral-mediated activation of NAc ERK2 enhanced susceptibility to both depression- and anxiety-related stimuli and increased cocaine-seeking behavior (conditioned place preference and reinstatement). These behavioral changes were associated with an increase in stubby and mushroom spines of NAc medium spiny neurons. Conversely, downregulation of ERK2 activation attenuated affect-related behavioral responses in the forced swim test and blunted cocaine’s rewarding effects without influencing NAc spine morphology.</div></div><div><h3>Conclusions</h3><div>NAc ERK2 contributes to stress-induced behavioral deficits, including anxiety- and depression-like phenotypes, while promoting cocaine-seeking behavior. These findings suggest that ERK2 signaling in the NAc plays a role in the comorbidity of these related syndromes.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 2","pages":"Article 100416"},"PeriodicalIF":4.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum BDNF Increase After 9-Month Contemplative Mental Training Is Associated With Decreased Cortisol Secretion and Increased Dentate Gyrus Volume: Evidence From a Randomized Clinical Trial","authors":"Lara M.C. Puhlmann ,&nbsp;Pascal Vrtička ,&nbsp;Roman Linz ,&nbsp;Sofie L. Valk ,&nbsp;Ioannis Papassotiriou ,&nbsp;George P. Chrousos ,&nbsp;Veronika Engert ,&nbsp;Tania Singer","doi":"10.1016/j.bpsgos.2024.100414","DOIUrl":"10.1016/j.bpsgos.2024.100414","url":null,"abstract":"<div><h3>Background</h3><div>In this study, we investigated whether mindfulness- and meditation-based mental training that improves stress regulation can upregulate BDNF (brain-derived neurotrophic factor), an important promoter of hippocampal neuroplasticity, and examined cortisol reduction as a mediating pathway.</div></div><div><h3>Methods</h3><div>In a randomized clinical trial, 332 healthy adults were randomly assigned to one of the 3 training cohorts or a passive control cohort. Training participants completed up to three 3-month-long modules targeting attention-based mindfulness, socio-affective skills, or socio-cognitive skills. We examined change in serum BDNF levels after each 3-month training interval; evaluated whether training effects were linked to reduced cortisol release in the long-term, diurnally, and when acutely stress-induced; and explored associations with hippocampal volume changes.</div></div><div><h3>Results</h3><div>In the combined training cohorts, BDNF increased significantly and cumulatively after 3-, 6-, and 9-month training relative to the pretraining baseline (3 month: <em>t</em>₅₁₆ = 3.57 [estimated increase: 1353 pg/mL], 6 month: <em>t</em>₅₁₆ = 3.45 [1557 pg/mL], 9 month: <em>t</em>₅₁₆ = 3.45 [2276 pg/mL]; all <em>p</em>s &lt; .001). After 9 months, training cohort BDNF was not higher than control cohort BDNF, which displayed unexplained variance. However, moderated mediation analysis showed that only training effects, and not control cohort BDNF change, were partially mediated by simultaneously reduced long-term cortisol release (3-month averages) measured in hair (15.1% mediation, <em>p</em> = .021). Individually greater BDNF increase after training correlated with more reduced long-term and stress-induced cortisol release. Moreover, greater BDNF increase after 9 months of training correlated with dentate gyrus volume increase (<em>t</em>₁₀₈ = 2.09, <em>p</em> = .039).</div></div><div><h3>Conclusions</h3><div>Longitudinal contemplative training may promote a neurobiological pathway from stress reduction to increased BDNF levels to enhanced hippocampal volume. However, single serum BDNF measurements can be unreliable for assessing long-term neurotrophic effects in healthy adults. Future studies should investigate nonspecific BDNF measurement effects before considering application in preventive health care.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 2","pages":"Article 100414"},"PeriodicalIF":4.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small Nucleolar RNAs and the Brain: Growing Evidence Supporting Their Role in Psychiatric Disorders","authors":"Juliette Salles ,&nbsp;Rixing Lin ,&nbsp;Gustavo Turecki","doi":"10.1016/j.bpsgos.2024.100415","DOIUrl":"10.1016/j.bpsgos.2024.100415","url":null,"abstract":"<div><div>Noncoding RNAs comprise most of the transcriptome and represent an emerging area of research. Among them, small nucleolar RNAs (snoRNAs) have emerged as a promising target because they have been associated with the development and evolution of several diseases, including psychiatric disorders. snoRNAs are expressed in the brain, with some showing brain-specific expression that indicates specific roles in brain development, function, and dysfunction. However, the role of snoRNAs in conditions that affect the brain needs further investigation to be better understood. This scoping review summarizes existing literature on studies that have investigated snoRNAs in psychiatry and offers insight into potential pathophysiological mechanisms to be further investigated in future research.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 2","pages":"Article 100415"},"PeriodicalIF":4.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In This Issue – November","authors":"","doi":"10.1016/j.bpsgos.2024.100403","DOIUrl":"10.1016/j.bpsgos.2024.100403","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100403"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guide for Authors","authors":"","doi":"10.1016/S2667-1743(24)00123-X","DOIUrl":"10.1016/S2667-1743(24)00123-X","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100410"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subscribers Page","authors":"","doi":"10.1016/S2667-1743(24)00121-6","DOIUrl":"10.1016/S2667-1743(24)00121-6","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100408"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Board Page","authors":"","doi":"10.1016/S2667-1743(24)00120-4","DOIUrl":"10.1016/S2667-1743(24)00120-4","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100407"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgments","authors":"","doi":"10.1016/j.bpsgos.2024.100404","DOIUrl":"10.1016/j.bpsgos.2024.100404","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100404"},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corticotropin-Releasing Factor Modulates Binge-Like Ethanol Drinking in a Sex-Dependent Manner: Impact of Amygdala Deletion and Inhibition of a Central Amygdala to Lateral Hypothalamus Circuit","authors":"Sophie C. Bendrath ,&nbsp;Hernán G. Méndez ,&nbsp;Anne M. Dankert ,&nbsp;Jose Manuel Lerma-Cabrera ,&nbsp;Francisca Carvajal ,&nbsp;Ana Paula S. Dornellas ,&nbsp;Sophia Lee ,&nbsp;Sofia Neira ,&nbsp;Harold Haun ,&nbsp;Eric Delpire ,&nbsp;Montserrat Navarro ,&nbsp;Thomas L. Kash ,&nbsp;Todd E. Thiele","doi":"10.1016/j.bpsgos.2024.100405","DOIUrl":"10.1016/j.bpsgos.2024.100405","url":null,"abstract":"<div><h3>Background</h3><div>Binge alcohol drinking is a dangerous behavior that can contribute to the development of more severe alcohol use disorder. Importantly, the rate and severity of alcohol use disorder has historically differed between men and women, suggesting that there may be sex differences in the central mechanisms that modulate alcohol (ethanol) consumption. Corticotropin-releasing factor (CRF) is a centrally expressed neuropeptide that has been implicated in the modulation of binge-like ethanol intake, and emerging data highlight sex differences in CRF systems.</div></div><div><h3>Methods</h3><div>In the current report, we characterized CRF+ neurocircuitry arising from the central nucleus of the amygdala (CeA) and innervating the lateral hypothalamus (LH) in the modulation of binge-like ethanol intake in male and female mice.</div></div><div><h3>Results</h3><div>Using chemogenetic tools, we found that silencing the CRF+ CeA to LH circuit significantly blunted binge-like ethanol intake in male but not female mice. Consistently, genetic deletion of CRF from neurons of the CeA blunted ethanol intake exclusively in male mice. Furthermore, pharmacological blockade of the CRF₁ receptor in the LH significantly reduced binge-like ethanol intake in male mice only, while CRF₂ receptor activation in the LH failed to alter ethanol intake in either sex. Finally, a history of binge-like ethanol drinking reduced <em>C</em><em>rf</em> messenger RNA levels in the CeA regardless of sex.</div></div><div><h3>Conclusions</h3><div>These observations provide novel evidence that CRF+ CeA to LH neurocircuitry is more sensitive for modulating binge-like ethanol intake in male mice, which may provide insight into the mechanisms that guide known sex differences in binge-like ethanol intake.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 1","pages":"Article 100405"},"PeriodicalIF":4.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}