Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"The gut-brain axis: Unveiling the impact of xenobiotics on neurological health and disorders","authors":"Sushruta Koppula ,&nbsp;Nitu Wankhede ,&nbsp;Ashishkumar Kyada ,&nbsp;Suhas Ballal ,&nbsp;Renu Arya ,&nbsp;Anurag Kumar Singh ,&nbsp;Monica Gulati ,&nbsp;Astha Sute ,&nbsp;Sanskruti Sarode ,&nbsp;Shruti Polshettiwar ,&nbsp;Vaibhav Marde ,&nbsp;Brijesh Taksande ,&nbsp;Aman Upaganlawar ,&nbsp;Mohammad Fareed ,&nbsp;Milind Umekar ,&nbsp;Spandana Rajendra Kopalli ,&nbsp;Mayur Kale","doi":"10.1016/j.pnpbp.2024.111237","DOIUrl":"10.1016/j.pnpbp.2024.111237","url":null,"abstract":"<div><div>The Gut-Brain Axis (GBA) is a crucial link between the gut microbiota and the central nervous system. Xenobiotics, originating from diverse sources, play a significant role in shaping this interaction. This review examines how these compounds influence neurotransmitter dynamics within the GBA. Environmental pollutants can disrupt microbial populations, impacting neurotransmitter synthesis—especially serotonin, gamma-aminobutyric acid (GABA), and dopamine pathways. Such disruptions affect mood regulation, cognition, and overall neurological function. Xenobiotics also contribute to the pathophysiology of neurological disorders, with changes in serotonin levels linked to mood disorders and imbalances in GABA and dopamine associated with anxiety, stress, and reward pathway disorders. These alterations extend beyond the GBA, leading to complications in neurological health, including increased risk of neurodegenerative diseases due to neuroinflammation triggered by neurotransmitter imbalances. This review provides a comprehensive overview of how xenobiotics influence the GBA and their implications for neurological well-being.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111237"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the role of environment in associative learning of nicotine-induced place preference conditioning in zebrafish","authors":"M.P. Faillace,&nbsp;L. Rocco,&nbsp;J. Ortiz,&nbsp;R. Bernabeu","doi":"10.1016/j.pnpbp.2024.111242","DOIUrl":"10.1016/j.pnpbp.2024.111242","url":null,"abstract":"<div><div>Environmental enrichment (EE) is a well-known strategy in animal behavior to improve the welfare and health of animals in captivity. EE provides animals with stimulating and engaging environments that promote natural behaviors, cognitive stimulation and stress reduction. EE turns out to be an important strategy to increase the validity and reproducibility of behavioral data. Zebrafish is a useful experimental model for pharmaceutical and toxicological screening to study mechanisms involved in behavioral flexibility. The present work examined for the first time whether exposure to an EE during conditioning in the conditioned place preference (EE-CPP) task modulates the rewarding properties of nicotine in zebrafish. Various combinations of preferred and avoided environments (via positive and aversive cues introduced in each compartment of the CPP tank) were tested in the EE-CPP task. Positive nicotine-CPP scores were obtained in all conditions tested, except when the aversive and preferred stimuli were placed in the same compartment. When two highly preferred stimuli (brown walls and plants) were associated with dots drawn on the floor of the nicotine-matched compartment, nicotine-CPP score was lower. These findings suggest that threatening stimuli in the environment where the drug is administered or consumed could disrupt conditioning and reduce drug rewarding effects. A series of other behavioral parameters corroborated EE-CPP scores. Our findings underscore the need for further research to better understand how these factors interact and influence an individual's vulnerability to nicotine addiction. The present study contributes to expand our understanding of the dynamics involved in the behavioral flexibility underlying nicotine addiction.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111242"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroanatomical subtypes of tobacco use disorder and relationship with clinical and molecular features","authors":"Mengzhe Zhang,&nbsp;Xiaoyu Niu,&nbsp;Jinghan Dang,&nbsp;Jieping Sun,&nbsp;Qiuying Tao,&nbsp;Weijian Wang,&nbsp;Shaoqiang Han,&nbsp;Jingliang Cheng,&nbsp;Yong Zhang","doi":"10.1016/j.pnpbp.2024.111235","DOIUrl":"10.1016/j.pnpbp.2024.111235","url":null,"abstract":"<div><h3>Background</h3><div>Individual neurobiological heterogeneity among patients with tobacco use disorder (TUD) hampers the identification of neuroimaging phenotypes.</div></div><div><h3>Methods</h3><div>The current study recruited 122 TUD individuals and 57 healthy controls, and obtained their 3D-T1 images. Heterogeneity through discriminative analysis (HYDRA) was applied to uncover the potential subtype of TUD where regional gray matter volume (GMV) was treated as the feature. Then we examined the clinical, neuroimaging and molecular characteristics of subtypes.</div></div><div><h3>Results</h3><div>Two distinct neuroanatomical subtypes were found. In subtype 1, TUD individuals showed decreased GMV in right orbitofrontal cortex (OFC), while subtype 2 exhibited distributed pattern of widely GMV increase. Moreover, subtype 1 showed older initial smoking age, longer duration of smoking than Subtype 2. Persistent smoking behavior in subtype 1 is more likely caused by substance dependence/addiction rather than psychosocial factors. GMV correlated negatively with cumulative tobacco exposure in Subtype 1 but not in Subtype 2. Besides, neuroanatomical aberrance in subtype 1 was mainly associated with dopamine system, while neuroanatomical abnormalities in subtype 2 were primarily associated with GABAa.</div></div><div><h3>Conclusions</h3><div>Overall, our results revealed two opposite neuroanatomical subtypes of TUD, which largely overlapped with their clinical and molecular features respectively. TUD subtypes taxonomy based on objective anatomy could help to facilitate the development of individualized treatment for TUD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111235"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Static and dynamic connectivity structure of white-matter functional networks across the adult lifespan","authors":"Zeqiang LinLi ,&nbsp;Kang Hu ,&nbsp;Qingdong Guo ,&nbsp;Shuixia Guo","doi":"10.1016/j.pnpbp.2025.111252","DOIUrl":"10.1016/j.pnpbp.2025.111252","url":null,"abstract":"<div><div>Aging of the human brain involves intricate biological processes, resulting in complex changes in structure and function. While the effects of aging on gray matter (GM) connectivity are extensively studied, white matter (WM) functional changes have received comparatively less attention. This study examines age-related WM functional dynamics using resting-state fMRI across the adult lifespan. We identified GM and WM functional networks (FNs) using k-means clustering. Static and dynamic analyses of WM functional network connectivity (FNC) were performed to explore age effects on WM-FNs and recurrent patterns of dynamic FNC. We identified 9 WM and 12 GM FNs. Age-related effects on WM FNC strength and WM-GM FNC dynamics included linear positive and U-shaped age trajectories in static FNC strength, and linear negative and inverted U-shaped trajectories in FNC temporal variability. Three distinct brain states with significant age-related differences were identified and validated. These findings were largely replicated in the validation analysis. High integration and low temporal variability in WM-GM FNC may indicate reduced adaptability of the network system in older adults, offering insights into brain aging processes.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111252"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multimodal neuroimaging meta-analysis of functional and structural brain abnormalities in attention-deficit/hyperactivity disorder.","authors":"Chao Chen, Shilin Sun, Ruoyi Chen, Zixuan Guo, Xinyue Tang, Guanmao Chen, Pan Chen, Guixian Tang, Li Huang, Ying Wang","doi":"10.1016/j.pnpbp.2024.111199","DOIUrl":"10.1016/j.pnpbp.2024.111199","url":null,"abstract":"<p><strong>Background: </strong>Numerous neuroimaging studies utilizing resting-state functional imaging and voxel-based morphometry (VBM) have identified variations in distinct brain regions among individuals with attention-deficit/hyperactivity disorder (ADHD). However, the results have been inconsistent.</p><p><strong>Methods: </strong>A comprehensive voxel-wise meta-analysis was performed on studies employing resting-state functional imaging and gray matter volume (GMV), examining discrepancies between individuals with ADHD and neurotypical controls (NCs). The analysis utilized the Seed-based d Mapping software.</p><p><strong>Results: </strong>A systematic review of the literature identified 21 functional imaging studies (595 ADHD and 564 controls) and 50 GMV studies (1907 ADHD and 1611 controls). In general, individuals with ADHD exhibited increased resting-state functional activity in the right parahippocampal gyrus and bilateral orbitofrontal cortex (OFC), as well as decreased resting-state functional activity in the bilateral cingulate cortex (including the posterior cingulate cortex [PCC], median cingulate cortex [MCC], and anterior cingulate cortex [ACC]). The VBM meta-analysis revealed decreased GMV in the bilateral OFC, right putamen (extending to right superior temporal gyrus [STG]), left inferior frontal gyrus (IFG), right superior frontal gyrus (SFG), ACC, and precentral gyrus among individuals with ADHD.</p><p><strong>Conclusions: </strong>The multimodal meta-analyses indicated that individuals with ADHD exhibit abnormalities in both function and structure in the bilateral OFC. In addition, a few regions exhibited only functional or only structural abnormalities in ADHD, such as in the limbic, prefrontal, primary sensorimotor regions.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111199"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporoparietal structural-functional coupling abnormalities in drug-naïve first-episode major depressive disorder","authors":"Qian Zhang ,&nbsp;Aoxiang Zhang ,&nbsp;Ziyuan Zhao ,&nbsp;Qian Li ,&nbsp;Yongbo Hu ,&nbsp;Xiaoqi Huang ,&nbsp;Graham J. Kemp ,&nbsp;Weihong Kuang ,&nbsp;Youjin Zhao ,&nbsp;Qiyong Gong","doi":"10.1016/j.pnpbp.2024.111211","DOIUrl":"10.1016/j.pnpbp.2024.111211","url":null,"abstract":"<div><h3>Introduction</h3><div>Major depressive disorder (MDD) is a debilitating and heterogeneous disease. Many MDD patients experience concurrent anxiety symptoms, often referred to as anxious depression (MDD-ANX). The relationships between network alterations in structural connectivity (SC) and functional connectivity (FC) in MDD and its anxiety-related subtype remain areas that require further investigation.</div></div><div><h3>Methods</h3><div>We investigated SC-FC coupling at the system and regional levels in 80 never-treated first-episode MDD patients and 80 healthy control (HC) subjects. For brain systems and regions showing significant between-group coupling differences, we further conducted subgroup comparisons between MDD-ANX, non-anxious depression (MDD-NANX) and HC. We also investigated topological features at the corresponding levels, and assessed the correlation patterns between significant coupling alterations and the topological and clinical characteristics.</div></div><div><h3>Results</h3><div>Relative to HC, MDD patients showed increased SC-FC coupling in the temporal system (right hippocampus and left superior temporal gyrus [STG]) but decreased coupling in the parietal system (right postcentral gyrus and left angular gyrus). These systems and regions were further characterized by disturbed inter-module connections and impaired structural network efficiency in MDD. Notably, SC-FC coupling of the right hippocampus was significantly increased in MDD-ANX compared to MDD-NANX, which further showed distinct correlation patterns with structural network efficiency.</div></div><div><h3>Conclusions</h3><div>Alterations in both SC-FC coupling and topological properties in the temporal and parietal regions provide insights into the interplay between the structural and functional network abnormalities in MDD. SC-FC coupling alterations in the right hippocampus, associated with structural nodal efficiency, may be implicated in the neuropathology of anxious depression.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111211"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative safety of prescribed Esketamine and ketamine in relation to renal and urinary disorders: A pharmacovigilance perspective","authors":"S. Chiappini ,&nbsp;A. Guirguis ,&nbsp;N. Schifano ,&nbsp;J.M. Corkery ,&nbsp;F. Semeraro ,&nbsp;A. Mosca ,&nbsp;G. D’Andrea ,&nbsp;G. Duccio Papanti ,&nbsp;D. Arillotta ,&nbsp;G. Floresta ,&nbsp;G. Martinotti ,&nbsp;F. Schifano","doi":"10.1016/j.pnpbp.2024.111213","DOIUrl":"10.1016/j.pnpbp.2024.111213","url":null,"abstract":"<div><div>Intranasal esketamine, approved with oral antidepressants for adults with treatment-resistant depression (TRD), is the S-enantiomer of ketamine and has higher potency and affinity for N-Methyl-<span>d</span>-Aspartate receptors. Administered intranasally, it offers rapid absorption and onset, essential for severe depressive symptoms or suicidal impulses. Comparative studies on esketamine and ketamine's urological safety profiles show esketamine has lower or comparable risks of renal and urinary disorders. Ketamine, however, has documented cases of nephrotoxicity and severe urological issues in recreational users.</div><div>The study aims to further evaluate and compare these profiles against other antidepressants and antipsychotics using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) data. ADR cases were reported to the FDA up to May 12, 2024, being drugs listed including esketamine, ketamine, quetiapine, aripiprazole, olanzapine, risperidone, citalopram, escitalopram, paroxetine, fluoxetine, sertraline, duloxetine, venlafaxine, amitriptyline, and clomipramine.</div><div>Risperidone showed the highest ADRs (107,418) and serious cases (71,515), with significant renal and urinary disorders reported, including acute kidney injury and urinary incontinence. Olanzapine, quetiapine, and aripiprazole also had high serious ADRs. Venlafaxine and fluoxetine were notable among antidepressants for acute kidney injury. Esketamine and ketamine were associated with lower urinary tract symptoms and nephrolithiasis. Disproportionality analysis revealed ketamine had higher odds of renal and urinary disorders compared to other drug classes, while esketamine had lower or comparable odds.</div><div>The data suggest a relatively favorable tolerability profile for these drugs, especially esketamine. However, the results highlight the necessity for more extensive studies to evaluate long-term safety and optimize treatment protocols.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111213"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neuropharmacology of kratom, a novel psychoactive natural product","authors":"MeShell Green ,&nbsp;Charles A. Veltri ,&nbsp;Walter C. Prozialeck ,&nbsp;Oliver Grundmann","doi":"10.1016/j.pnpbp.2024.111215","DOIUrl":"10.1016/j.pnpbp.2024.111215","url":null,"abstract":"<div><div>Kratom (<em>Mitragyna speciosa,</em> Korth.) is a tropical tree that is indigenous to Southeast Asia. When ingested, kratom leaves or decoctions from the leaves have been reported to produce complex stimulant and opioid-like effects. For generations native populations in Southeast Asia have used kratom products to stave off fatigue, improve mood, alleviate pain and manage symptoms of opioid withdrawal. Over the past 15–20 years, kratom use has spread to Western nations including the United States, where many individuals are using kratom products for the self-management of pain, opioid use disorder, anxiety and depression. The increased use of kratom has triggered a surge in research into the biochemistry, pharmacology and behavioral effects of kratom and its active constituents, especially mitragynine and 7-hydroxymitragynine. In this review, we highlight some of the recent animal studies showing that kratom and its constituent compounds have potential beneficial effects in animal models of pain, anxiety, depression and opioid dependence. We also highlight studies showing that kratom can modulate the functioning of opioid, noradrenergic, serotonergic and dopaminergic systems. The highlighted studies strongly suggest that kratom and its constituents may form the basis for the development of novel therapeutic agents.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111215"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A two-sample study on the relationship between polygenic risk score of serotonergic polymorphisms and social phobia: Interpersonal adaptability as a mediator","authors":"Yuting Yang ,&nbsp;Qi Lan ,&nbsp;Wenting Liang ,&nbsp;Mingzhu Zhou ,&nbsp;Wenping Zhao ,&nbsp;Pingyuan Gong","doi":"10.1016/j.pnpbp.2024.111220","DOIUrl":"10.1016/j.pnpbp.2024.111220","url":null,"abstract":"<div><h3>Backgrounds</h3><div>The influence of serotonin function on social phobia has been well-documented, yet the polygenic risk score of serotonergic polymorphisms for social phobia remains unclear.</div></div><div><h3>Methods</h3><div>We assessed two aspects of social phobia (i.e., social interaction anxiety and social phobia scrutiny fear) and created a polygenic risk score of seven serotonergic polymorphisms in two independent samples.</div></div><div><h3>Results</h3><div>The results from both samples indicated that a greater polygenic risk score, denoting a higher risk of anxiety, was associated with higher levels of social interaction anxiety and social phobia scrutinizing fear. Interestingly, the association between polygenic risk score and social interaction anxiety was mediated by interpersonal adaptability.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate the importance of serotonergic polymorphisms in social phobia and unveil a psychological pathway whereby interpersonal adaptability mediates the effect of serotonergic polymorphisms on social phobia.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111220"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal exposure to valproic acid induces sex-specific alterations in rat cortical and hippocampal neuronal structure and function in vitro","authors":"Olivia O.F. Williams ,&nbsp;Madeleine Coppolino ,&nbsp;Cecilia B. Micelli ,&nbsp;Ryan T. McCallum ,&nbsp;Paula T. Henry-Duru ,&nbsp;Joshua D. Manduca ,&nbsp;Jasmin Lalonde ,&nbsp;Melissa L. Perreault","doi":"10.1016/j.pnpbp.2024.111222","DOIUrl":"10.1016/j.pnpbp.2024.111222","url":null,"abstract":"<div><div>There are substantial differences in the characteristics of males and females with an autism spectrum disorder (ASD), yet there is little knowledge surrounding the mechanistic underpinnings of these differences. The valproic acid (VPA) rodent model is based upon the human fetal valproate spectrum disorder, which is associated with increased risk of developing ASD. This model, which displays significant social, learning, and memory alterations, has therefore been widely used to further our understanding of specific biological features of ASD. However, to date, almost all of the studies employing this model have used male rodents. To fill this knowledge gap, we evaluated sex differences for neuronal activity, morphology, and glycogen synthase kinase-3 (GSK-3) signaling in primary cortical (CTX) and hippocampal (HIP) neurons prepared from rats exposed to VPA <em>in utero</em>. <em>In vivo</em>, sex-specific VPA-induced alterations in the frontal CTX transcriptome at birth were also determined. Overall, VPA induced more robust changes in neuronal function and structure in the CTX than in the HIP. Male- and female-derived primary CTX neurons from rats exposed to prenatal VPA had elevated activity and showed more disorganized firing. In the HIP, only the female VPA neurons showed elevated firing, while the male VPA neurons exhibited disorganized activity. Dendritic arborization of CTX neurons from VPA rats was less complex in both sexes, though this was more pronounced in the females. Conversely, both female and male HIP neurons from VPA rats showed elevated complexity distal to the soma. Female VPA CTX neurons also had an elevated number of dendritic spines. The relative activity of the α and β isoforms of GSK-3 were suppressed in both female and male VPA CTX neurons, with no changes in the HIP neurons. On postnatal day 0, alterations in CTX genes associated with neuropeptides (<em>e.g.</em>, <em>penk</em>, <em>pdyn</em>) and receptors (<em>e.g.</em>, <em>drd1</em>, <em>adora2a</em>) were seen in both sexes, though they were downregulated in females and upregulated in males<em>.</em> Together these findings suggest that substantial sex differences in neuronal structure and function in the VPA model may have relevance to the reported sex differences in idiopathic ASD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111222"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}