Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Relationships between clinical symptoms, cognitive functioning, and TMS-evoked potential features in patients with major depressive disorder","authors":"Jiaxin Li ,&nbsp;Xingxing Li ,&nbsp;Junyao Liu ,&nbsp;Shuochi Wei ,&nbsp;Dongsheng Zhou ,&nbsp;Dongmei Wang ,&nbsp;Xiangyang Zhang","doi":"10.1016/j.pnpbp.2024.111184","DOIUrl":"10.1016/j.pnpbp.2024.111184","url":null,"abstract":"<div><h3>Background</h3><div>Cognitive impairment is a common clinical symptom of patients with major depressive disorder (MDD). Transcranial magnetic stimulation-evoked potentials (TEPs) detect cortical excitability and connectivity and provide potential biomarkers for MDD patients and their cognitive impairment<em>.</em> This study aimed to investigate the interrelationships between clinical symptoms, cognitive function, and electrophysiological marker TEPs in patients with MDD.</div></div><div><h3>Methods</h3><div>A total of 117 participants were recruited, including 59 MDD patients and 58 healthy controls. Clinical symptoms were assessed by the Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale, and cognitive functioning was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). TEPs were recorded by transcranial magnetic stimulation combined with electroencephalography (TMS-EEG).</div></div><div><h3>Results</h3><div>MDD patients exhibited lower RBANS total (<em>P</em> &lt; 0.001), immediate memory (<em>P</em> = 0.001), language (<em>P</em> = 0.003), attention (<em>P</em> &lt; 0.001), and delayed memory (<em>P</em> = 0.008) scores than HCs. Patients with MDD had larger amplitudes for N100 (<em>P</em> = 0.040) and N280 (<em>P</em> = 0.037)<em>,</em> compared to HCs<em>.</em> Correlation analysis indicated significant correlations between the following RBANS scores and TEPs: language and N45 amplitude (<em>r</em> = 0.222, <em>P</em> = 0.024), language and P60 amplitude (<em>r</em> = 0.278, <em>P</em> = 0.004), attention and P180 amplitude (<em>r</em> = 0.213, <em>P</em> = 0.030), RBANS total score and P30 amplitude (<em>r</em> = 0.198, <em>P</em> = 0.044), visuospatial/constructional index and N100 amplitude (<em>r</em> = −0.272, <em>P</em> = 0.005).</div></div><div><h3>Conclusion</h3><div>The results of this study indicate that cortical dysfunction and cognitive impairment are present in patients with MDD and that there is a strong correlation between them, suggesting that TEPs detected by the TMS-EEG may be used as a biomarker for MDD patients and their cognitive impairment.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111184"},"PeriodicalIF":5.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645214","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":"The immune regulatory mechanism of ketamine-induced psychiatric disorders: A new perspective on drug-induced psychiatric symptoms","authors":"Peipei Wang ,&nbsp;Junmei Hu ,&nbsp;Congliang Chen ,&nbsp;Zihan Jiang ,&nbsp;Yu Zhang ,&nbsp;Kexin Lin ,&nbsp;Linchuan Liao ,&nbsp;Xia Wang","doi":"10.1016/j.pnpbp.2024.111194","DOIUrl":"10.1016/j.pnpbp.2024.111194","url":null,"abstract":"<div><div>Ketamine, a psychoactive substance strictly regulated by international drug conventions, is classified as a “new type drug” due to its excitatory, hallucinogenic, or inhibitory effects. The etiology of ketamine-induced psychiatric symptoms is multifaceted, with the immune regulatory mechanism being the most prominent among several explanatory theories. In recent years, the interaction between the immune system and nervous system have garnered significant attention in neuropsychiatric disorder research. Notably, the infiltration of peripheral lymphocytes into the central nervous system has emerged as an early hallmark of certain neuropsychiatric disorders. However, a notable gap exists in the current literature, regarding the immune regulatory mechanisms, specifically the peripheral immune alterations, associated with ketamine-induced psychiatric symptoms. To address this void, this article endeavors to provide a comprehensive overview of the pathophysiological processes implicated in psychiatric disorders or symptoms, encompassing those elicited by ketamine. This analysis delves into aspects such as nerve damage, alterations within the central immune system, and the regulation of the peripheral immune system. By emphasizing the intricate crosstalk between the peripheral immune system and the central nervous system, this study sheds light on their collaborative role in the onset and progression of psychiatric diseases or symptoms. This insight offers fresh perspectives on the underlying mechanisms, diagnosis and therapeutic strategies for mental disorders stemming from drug abuse.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111194"},"PeriodicalIF":5.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632833","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":"Transcriptional signatures of gray matter volume changes in mild traumatic brain injury","authors":"Lu Wang ,&nbsp;He Wang ,&nbsp;Yijing Zhang ,&nbsp;Mengjing Cai ,&nbsp;Zhihui Zhang ,&nbsp;Minghuan Lei ,&nbsp;Yujie Zhang ,&nbsp;Jiaxuan Zhao ,&nbsp;Ying Wang ,&nbsp;Jinglei Xu ,&nbsp;Ying Zhai ,&nbsp;Jinghan Sun ,&nbsp;Qi An ,&nbsp;Wenjie Cai ,&nbsp;Yifan Jiang ,&nbsp;Feng Liu ,&nbsp;Yanmin Peng ,&nbsp;Lining Guo","doi":"10.1016/j.pnpbp.2024.111195","DOIUrl":"10.1016/j.pnpbp.2024.111195","url":null,"abstract":"<div><h3>Background</h3><div>Neuroimaging studies have shown that patients with mild traumatic brain injury (mTBI) often exhibit changes in gray matter volume (GMV) in the brain. However, the results regarding these changes are inconsistent, and the underlying molecular mechanisms remain unclear. This study aimed to investigate GMV changes in mTBI patients and uncover the molecular mechanisms driving these alterations.</div></div><div><h3>Methods</h3><div>We conducted a neuroimaging meta-analysis on nine studies, involving 396 mTBI patients and 338 healthy controls, to identify consistent patterns of GMV changes. Additionally, we utilized the Allen Human Brain Atlas database to explore transcriptome-neuroimaging spatial correlations, identifying genes whose expression profiles are linked to GMV changes in mTBI patients. Enrichment analyses were also performed to determine the biological significance of the altered GMV-related genes.</div></div><div><h3>Results</h3><div>We observed consistent GMV increases in the bilateral middle cingulate/paracingulate gyri, right striatum, and right dorsolateral superior frontal gyrus, along with GMV decreases in the right insula and left lingual gyrus. Moreover, we found spatial associations between mTBI-related GMV changes and the expression of 977 genes, which were primarily enriched in specific biological processes, body tissues, and developmental time windows of the cerebral cortex.</div></div><div><h3>Conclusion</h3><div>Our findings improve the understanding of GMV abnormalities in mTBI patients and provide insights into the molecular mechanisms underlying these changes.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111195"},"PeriodicalIF":5.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632835","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":"Social isolation intensifies adgrl3.1-related externalizing and internalizing behaviors in zebrafish","authors":"Barbara D. Fontana ,&nbsp;Nancy Alnassar ,&nbsp;William H.J. Norton ,&nbsp;Matthew O. Parker","doi":"10.1016/j.pnpbp.2024.111193","DOIUrl":"10.1016/j.pnpbp.2024.111193","url":null,"abstract":"<div><div>Externalizing disorders (EDs) are characterized by outward-directed behaviors such as aggression and hyperactivity. They are influenced by gene-environment interactions, yet our understanding of the genetic predispositions and environmental contexts that give rise to them is incomplete. Additionally, people with EDs often exhibit comorbid internalizing symptoms, which can complicate the clinical presentation and treatment strategies. Following on from our previous studies, we examined genes x environment interaction as a risk factor for EDs by looking at internalizing and externalizing behaviors after social isolation. Specifically, we subjected <em>adgrl3.1</em> knockout zebrafish — characterized by hyperactivity and impulsivity — to a 2-week social isolation protocol. We subsequently assessed the impact on anxiety-like behavior, abnormal repetitive behaviors, working memory, and social interactions. Genotype-specific additive effects emerged, with socially isolated <em>adgrl3.1</em> knockout fish exhibiting intensified comorbid phenotypes, including increased anxiety, abnormal repetitive behaviors, reduced working memory, and altered shoaling, when compared to WT fish. The findings demonstrate that genetic predispositions interact with environmental stressors, such as social isolation, to exacerbate both externalizing and internalizing symptoms. This underlines the necessity for comprehensive diagnostic and intervention strategies.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111193"},"PeriodicalIF":5.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632831","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 new pharmacological strategy against treatment-resistant depression","authors":"Juan Pedro Pineda-Gómez ,&nbsp;Carmelo Millón ,&nbsp;Noelia Cantero-García ,&nbsp;Marta Flores-Gómez ,&nbsp;David Ladrón de Guevara-Miranda ,&nbsp;Antonio Flores-Burgess ,&nbsp;Zaida Díaz-Cabiale","doi":"10.1016/j.pnpbp.2024.111191","DOIUrl":"10.1016/j.pnpbp.2024.111191","url":null,"abstract":"<div><div>Major depressive disorder affects more than 50 million people in the world. However, 50% of patients don't respond to two or more drugs or psychotherapeutic treatments, named treatment-resistant depression (TRD). In this work, we propose a new augmentation treatment against TRD based on combining Fluoxetine (FLX) and the N-terminal fragment Galanin, GAL(1–15). In Wistar Kyoto (WKY) rats, akin to endogenous depression genetically, we evaluate GAL(1–15)’s impact on FLX-induced behaviours on tests measuring despair and anhedonia. We explored GALR2 involvement using the antagonist M871 and an in vivo model with siRNA 5-HT1A knockdown. Also, the 5-HT1AR was analyzed by autoradiography binding in several brain regions. We analyze the corticosterone levels and a dexamethasone-suppressed corticotropin-releasing hormone stimulation to study the HPA axis regulation. Our results shows that only the combination of FLX + GAL(1–15) induced antidepressant effects in the WKY animals in Behavioural tests related to despair. This combination also reduced corticosterone levels in the WKY animals and modulated the functional characteristics of the serotoninergic receptor 5-HT1A in the prefrontal cortex. These novel results suggest combining GAL(1–15) with FLX is a new potentiation strategy in TRD cases. It shows the innovative potential of the interactions between the galaninergic and serotonergic systems to find new strategies and drugs against resistant depression.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111191"},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632837","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":"Resveratrol prevents offspring's behavioral impairment associated with immunogenic stress during pregnancy","authors":"Rener Mateus Francisco Duarte ,&nbsp;Erika Renata Ribeiro-Barbosa ,&nbsp;Frederico Rogério Ferreira ,&nbsp;Foued Salmen Espindola ,&nbsp;Vanessa Beatriz Monteiro Galassi Spini","doi":"10.1016/j.pnpbp.2024.111188","DOIUrl":"10.1016/j.pnpbp.2024.111188","url":null,"abstract":"<div><div>Evidence suggests that prenatal maternal immunological stress is associated with an increased risk of neurological and psychiatric disorders in the developing offspring. Protecting the embryo during this critical period of neurodevelopment, when the brain is especially vulnerable, is therefore crucial. Polyphenols, with their antioxidant and anti-inflammatory properties, offer promising therapeutic approaches. This study demonstrated a series of behavioral changes induced by maternal immune activation (MIA) triggered by an antigenic solution derived from the H1N1 virus. These changes include significant differences in anxiety and risk assessment behaviors, increased immobility in the forced swim test, impairments in memory and object recognition, and social deficits resembling autism. The phenolic compound resveratrol (RSV) was evaluated for its in vitro antioxidant capacity and characterized using infrared spectroscopy. Administering RSV from embryonic day 14 (E14) to embrionyc day 19 (E19) during MIA effectively reduced its harmful effects on the offspring. This was evidenced by a significant restoration of social behaviors, memory, and recognition, as well as anxiolytic and antidepressant effects in the adult offspring. These findings contribute to new therapeutic strategies for preventing psychiatric disorders associated with neurodevelopmental stressors.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111188"},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632769","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":"MicroRNA-specific targets for neuronal plasticity, neurotransmitters, neurotrophic factors, and gut microbes in the pathogenesis and therapeutics of depression","authors":"Cong-Ya Chen,&nbsp;Yu-Fei Wang,&nbsp;Lan Lei,&nbsp;Yi Zhang","doi":"10.1016/j.pnpbp.2024.111186","DOIUrl":"10.1016/j.pnpbp.2024.111186","url":null,"abstract":"<div><div>Depression is of great concern because of the huge burden, and it is impacted by various epigenetic modifications, e.g., histone modification, covalent modifications in DNA, and silencing mechanisms of non-coding protein genes, e.g., microRNAs (miRNAs). MiRNAs are a class of endogenous non-coding RNAs. Alternations in specific miRNAs have been observed both in depressive patients and experimental animals. Also, miRNAs are highly expressed in the central nervous system and can be delivered to different tissues via tissue-specific exosomes. However, the mechanism of miRNAs' involvement in the pathological process of depression is not well understood. Therefore, we summarized and discussed the role of miRNAs in depression. Conclusively, miRNAs are involved in the pathology of depression by causing structural and functional changes in synapses, mediating neuronal regeneration, differentiation, and apoptosis, regulating the gut microbes and the expression of various neurotransmitters and BDNF, and mediating inflammatory and immune responses. Moreover, miRNAs can predict the efficacy of antidepressant medications and explain the mechanism of action of antidepressant drugs and aerobic exercise to prevent and assist in treating depression.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111186"},"PeriodicalIF":5.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632839","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":"Sigma-1 receptor modulation by fluvoxamine ameliorates valproic acid-induced autistic behavior in rats: Involvement of chronic ER stress modulation, enhanced autophagy and M1/M2 microglia polarization","authors":"Ahmed F. Mohamed ,&nbsp;Mohamad A. El-Gammal ,&nbsp;Mohammed F. EL-Yamany ,&nbsp;Ahmed E. Khodeir","doi":"10.1016/j.pnpbp.2024.111192","DOIUrl":"10.1016/j.pnpbp.2024.111192","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a neurodevelopmental disorder. While, fluvoxamine (FVX) is an antidepressant and widely prescribed to ASD patients, clinical results are inconclusive and the mechanism of FVX in the management of ASD is unclear. This study determined the potential therapeutic impact of FVX, a sigma-1 receptor (S1R) agonist, against the valproic acid (VPA)-induced model of autism. On gestational day 12.5, Wistar pregnant rats were given a single intraperitoneal (i.p.) injection of either VPA (600 mg/kg) or normal saline (10 mL/kg, vehicle-control). Starting on postnatal day (PND) 21 to PND 50, FVX (30 mg/kg, P·O. daily) and NE-100, (S1R) antagonist, (1 mg/kg, i.p. daily) were given to male pups. Behavior tests and histopathological changes were identified at the end of the experiment. In addition, the cerebellum biomarkers of endoplasmic reticulum (ER) stress and autophagy were assessed. Microglial cell polarization to M1 and M2 phenotypes was also assessed. FVX effectively mitigated the histopathological alterations in the cerebellum caused by VPA. FVX enhanced sociability and stereotypic behaviors in addition to its noteworthy impact on autophagy enhancement, ER stress deterioration, and controlling microglial cell polarization. The current investigation confirmed that the S1R agonist, FVX, can lessen behavioral and neurochemical alterations in the VPA-induced rat model of autism.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111192"},"PeriodicalIF":5.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607497","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":"Plasma neurofilament light chain levels are associated with delirium tremens in patients with alcohol use disorder","authors":"Yu-Chi Hou ,&nbsp;Francesco Bavato ,&nbsp;Tung-Hsia Liu ,&nbsp;Hu-Ming Chang ,&nbsp;Hsiang-Wei Kuo ,&nbsp;Shih-Chun Meng ,&nbsp;Yu-Li Liu ,&nbsp;Ming-Chyi Huang","doi":"10.1016/j.pnpbp.2024.111189","DOIUrl":"10.1016/j.pnpbp.2024.111189","url":null,"abstract":"<div><div>Delirium tremens (DT) is the most severe and life-threatening manifestation of alcohol withdrawal. Prompt identification and treatment are crucial in the clinical management of DT, but laboratory markers in this context are still lacking. Neurofilament light chain (NfL) has been proposed as a novel blood marker of neuroaxonal pathology. Therefore, we investigated the association between plasma NfL levels on admission and the occurrence of DT in patients with alcohol use disorder (AUD). NfL levels were measured on admission in 224 patients with AUD undergoing alcohol withdrawal treatment and in 116 healthy individuals. We monitored patients with AUD during the following 2 weeks of hospitalization and categorized them according to the prospective occurrence of DT (<em>n</em> = 25) or not (<em>n</em> = 199). Plasma NfL levels at admission were highest in patients who later developed DT, compared to AUD patients without DT, and healthy individuals (63.1 ± 47.2, 24.0 ± 22.4, 11.8 ± 6.1 pg/mL, respectively, <em>p</em> &lt; 0.001). Receiver operating characteristic analysis revealed that a cut-off NfL level of 27.2 pg/mL could discriminate AUD patients who later developed DT (sensitivity: 80.0 %; specificity: 72.4 %; area under the curve: 0.84, <em>p</em> &lt; 0.001), with an odds ratio of 9.43 (95 % CI 3.26–27.32; <em>p</em> &lt; 0.001) for the risk of developing DT. Our findings suggest that NfL levels at admission may predict DT occurrence in patients with AUD and implicate neuroaxonal pathology in the pathophysiology of DT. Further research is needed to validate these findings and to explore the underlying neurobiological mechanisms.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111189"},"PeriodicalIF":5.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607487","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":"Soluble epoxide hydrolase deletion rescues behavioral and synaptic deficits by AMPK-mTOR pathway in autism animals","authors":"Ming-Chia Chu ,&nbsp;Han-Fang Wu ,&nbsp;Chi-Wei Lee ,&nbsp;Chi-Chun Wu ,&nbsp;Hsiang Chi ,&nbsp;Chiung-Yuan Ko ,&nbsp;Yi-Chao Lee ,&nbsp;Chih-Wei Tang ,&nbsp;Po See Chen ,&nbsp;Hui-Ching Lin","doi":"10.1016/j.pnpbp.2024.111190","DOIUrl":"10.1016/j.pnpbp.2024.111190","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social defects often accompanied with emotional comorbidities. Aberrations in synaptic function and plasticity are the core feature in the pathophysiology of ASD. Targeting soluble epoxide hydrolase (sEH) has been found to exert protection in a wide-range of pathological conditions. However, the regulation of sEH deficiency on the synaptic deficits of ASD and the underlying mechanisms remain unclear. The valproate (VPA)-treated ASD animal model with genetic sEH knockout was applied in the present study. The results showed that the sEH expression was significantly increased in the prefrontal cortex of VPA-treated animals. Although no effect was found on tail malformation and body weight loss, genetic sEH deletion alleviated social deficits, and fear learning and memory extinction in the VPA-treated mice. After a series of electrophysiological assessments, we found that the beneficial effects of sEH deletion focused on the long-term synaptic plasticity, rather than presynaptic efficiency, in the VPA-treated mice. Furthermore, we observed that the dysregulated AMPK-mTOR pathway was restored under genetic sEH deletion in VPA-treated mice. Taken together, these findings uncovered an important role of sEH deficiency in the synaptic dysfunctions of ASD mediated by AMPK-mTOR pathway, providing a novel therapeutic target for ASD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111190"},"PeriodicalIF":5.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607498","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}