Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Local cortical structure pattern and genetic links in schizophrenia: An MRI and CRISPR/Cas9 study","authors":"Pei-Shan Hou ,&nbsp;Shu-Fei Lin ,&nbsp;Jun-Ding Zhu ,&nbsp;Chih-Yun Chung ,&nbsp;Shih-Jen Tsai ,&nbsp;Albert C. Yang","doi":"10.1016/j.pnpbp.2025.111270","DOIUrl":"10.1016/j.pnpbp.2025.111270","url":null,"abstract":"<div><div>While the etiology of schizophrenia (SZ) remains elusive, its diverse phenotypes suggest the involvement of distinct functional cortical areas, and the heritability of SZ implies the underlying genetic factors. This study aimed to integrate imaging and molecular analyses to elucidate the genetic underpinnings of SZ. We investigated the local cortical structural pattern changes in Brodmann areas (BAs) by calculating the cortical structural pattern index (SPI) using magnetic resonance imaging analysis from 194 individuals with SZ and 330 controls. Significant local structural changes were detected in certain Brodmann areas in symmetric or asymmetric patterns, such as symmetric changes in the BA4 primary motor area and BA23 part of posterior cingulate cortex, and asymmetric changes in the BA13 insula, BA11 inferior orbitofrontal area, and BA 24, and BA 31 cingulate cortex. Following genome-wide association tests, we found genetic variants and SNP-mapped genes and verified the areal preferential expression profiles in the developing human and mouse neocortex. Finally, we performed a loss-of-function analysis using the CRISPR/Cas9 system to investigate the effects of disrupting the SZ-related SNP-mapped Morf4l1, Reep3, or Tmed3 gene on cortical cell fate to understand their roles in generating appropriate composition of cortical neurons. This study outlines a pipeline for identifying local structural changes, associated genetic causes, and potential molecular mechanisms underlying mental disorders. Additionally, these data shed light on establishing a structurally integral cerebral cortex for higher cognitive functions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111270"},"PeriodicalIF":5.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043350","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":"Subdiaphragmatic vagotomy reduces hypothalamic oxytocin expression and blood levels after oral MDMA administration in male rats","authors":"Yong Yue ,&nbsp;Xiayun Wan ,&nbsp;Guilin Liu ,&nbsp;Tingting Zhu ,&nbsp;Dan Xu ,&nbsp;Mingming Zhao ,&nbsp;Yi Cai ,&nbsp;Rumi Murayama ,&nbsp;Hirofumi Hashimoto ,&nbsp;Naohiko Anzai ,&nbsp;Kenji Hashimoto","doi":"10.1016/j.pnpbp.2025.111260","DOIUrl":"10.1016/j.pnpbp.2025.111260","url":null,"abstract":"<div><div>3,4-Methylenedioxymethamphetamine (MDMA) is a widely recognized entactogen frequently used recreationally. It is known for its interaction with the serotonin and oxytocin systems, which underlie its entactogenic effects in humans. Recently, we demonstrated that the gut-brain axis, mediated by the subdiaphragmatic vagus nerve, contributes to MDMA-induced resilience enhancement in rodents. This study investigates whether subdiaphragmatic vagotomy (SDV) affects plasma oxytocin levels and the expression of oxytocin and c-Fos in the hypothalamus following a single oral dose of MDMA in rats. SDV significantly reduced baseline plasma oxytocin levels and oxytocin expression in the paraventricular and supraoptic nuclei of the hypothalamus. Furthermore, SDV markedly attenuated MDMA-induced increases in plasma oxytocin and the expression of oxytocin and c-Fos in these hypothalamic regions. These findings suggest that the subdiaphragmatic vagus nerve plays a critical role in brain-body communication, mediating MDMA's pharmacological effects on the oxytocin system.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111260"},"PeriodicalIF":5.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043356","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":"Lycopene mitigates paclitaxel-induced cognitive impairment in mice; Insights into Nrf2/HO-1, NF-κB/NLRP3, and GRP-78/ATF-6 axes","authors":"Nora Zakaria ,&nbsp;Esther T. Menze ,&nbsp;Doaa A. Elsherbiny ,&nbsp;Mariane G. Tadros ,&nbsp;Mina Y. George","doi":"10.1016/j.pnpbp.2025.111262","DOIUrl":"10.1016/j.pnpbp.2025.111262","url":null,"abstract":"<div><div>Chemotherapy-induced cognitive impairment, referred to as “chemobrain”, is widely acknowledged as a significant adverse effect of cancer therapy. Paclitaxel, a chemotherapeutic drug, has been reported to cause cognitive impairment clinically and in animal models. However, the precise mechanisms are not fully understood. The current study explored the potential neuroprotective effect of lycopene in paclitaxel-induced cognitive impairment in mice and its potential underlying mechanisms. Mice were randomly allocated into six groups: control, paclitaxel-treated (10 mg/kg), lycopene-treated (5, 10, and 20 mg/kg) + paclitaxel, and lycopene alone-treated (20 mg/kg) groups. The effect of lycopene treatment on behavioral function and histological examination was assessed. Lycopene (20 mg/kg) was selected for additional investigation into the underlying mechanisms. Lycopene treatment counteracted paclitaxel-induced oxidative stress by reducing lipid peroxidation and enhancing catalase levels. Additionally, lycopene-treated mice demonstrated a significant elevation in nuclear factor erythroid 2-related factor 2 with no significant effect on hemeoxygenase-1. Moreover, paclitaxel administration elevated endoplasmic reticulum stress markers; glucose-regulated protein78, activating Transcription Factor 6, C/EBP <em>homologous protein,</em> and apoptosis marker annexin V which were significantly reduced by lycopene treatment. Furthermore, lycopene mitigated paclitaxel-induced neuroinflammation through the reduction of the levels of the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome axis markers; nuclear factor-κB, NLRP3, caspase-1, interleukin-1β, and interleukin-18. Our study findings may provide new evidence that lycopene mitigates paclitaxel-induced cognitive impairment in mice by reversing oxidative stress, endoplasmic reticulum stress, and inflammatory mechanisms.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111262"},"PeriodicalIF":5.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029624","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":"Roles of cerebrospinal fluid metabolites in mediating the relationship between cathepsins and narcolepsy type 1: A comprehensive Mendelian randomization analysis","authors":"Yanjuan Wu ,&nbsp;Qiming Gan ,&nbsp;Xiaofen Su ,&nbsp;Yutong Ding ,&nbsp;Quanzhen Liu ,&nbsp;Jingcun Wang ,&nbsp;Yuting Zhang ,&nbsp;Nuofu Zhang ,&nbsp;Kang Wu","doi":"10.1016/j.pnpbp.2025.111263","DOIUrl":"10.1016/j.pnpbp.2025.111263","url":null,"abstract":"<div><h3>Introduction</h3><div>To investigate the potential causal relationship between cathepsins and Narcolepsy Type 1 (NT1), along with the mediating influence of cerebrospinal fluid metabolites.</div></div><div><h3>Method</h3><div>We performed a comprehensive Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) data. Data on nine plasma cathepsins and 338 cerebrospinal fluid metabolites were sourced from the IEU OpenGWAS database, and NT1 were obtained from the FinnGen consortium's R10 release. Univariate MR (UVMR), multivariate MR (MVMR) and gene co-localization analyses were used to explore the potential causal relationship between cathepsins and NT1. In addition, mediation analyses were performed to explore the role of cerebrospinal fluid metabolites in mediating the relationship.</div></div><div><h3>Result</h3><div>In UVMR study, we identified a significant positive association between genetically elevated levels of plasma cathepsin B (OR = 2.022, 95 % CI: 1.456–2.809, <em>p</em> &lt; 0.01) and cathepsin F (OR = 0.676, 95 % CI: 0.473–0.966, <em>p</em> = 0.031) with NT1. However, in the MVMR analysis, only cathepsin B maintained a consistent effect (OR = 1.920, 95 % CI: 1.378–2.675, <em>p</em> &lt; 0.001). Subsequent co-localization analysis indicated shared causal variants between cathepsin B and NT1, further highlighting the robustness of our findings. Additionally, mediation MR revealed that the association between cathepsin B and NT1 was mediated by sphingomyelin and 1-(1-alkenyl-palmitoyl1)-2-propenoyl-gpc, accounting for 2.6 % and 4.7 % of the effect, respectively.</div></div><div><h3>Conclusion</h3><div>Our findings suggest a probable causal relationship between increased cathepsin B levels and NT1, with the potential of cerebrospinal fluid fatty acid metabolism disorder playing a mediating role in the development of this association. This indicates the potential of cathepsin B as a promising biomarker for NT1, highlighting significant implications for the diagnosis and treatment of this condition.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111263"},"PeriodicalIF":5.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025850","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":"Unraveling the genetic links between depression and type 2 diabetes","authors":"Ancha Baranova ,&nbsp;Dongming Liu ,&nbsp;Vikas Chandhoke ,&nbsp;Hongbao Cao ,&nbsp;Fuquan Zhang","doi":"10.1016/j.pnpbp.2025.111258","DOIUrl":"10.1016/j.pnpbp.2025.111258","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes (T2D) is a chronic metabolic disorder that has high comorbidity with mental disorders. The genetic relationships between T2D and depression are far from being well understood.</div></div><div><h3>Methods</h3><div>We performed genetic correlation, polygenic overlap, Mendelian randomization (MR) analyses, cross-trait meta-analysis, and Bayesian colocalization analysis to assess genetic relationships between T2D and depression, in the forms of major depressive disorder (MDD) and depressed affect (DAF). Then, the summary data-based MR (SMR) analysis was performed to prioritize genes contributing to MDD and to T2D from functional perspective. MDD-driven signaling pathways were constructed to understand the influence of MDD on T2D at the molecular level.</div></div><div><h3>Results</h3><div>T2D has positive genetic correlations both with MDD (r_g = 0.14) and with DAF (r_g = 0.19). The polygenic overlap analysis showed that about 60 % of causal variants for T2D are shared with MDD and DAF. The MR analysis indicated that genetic liabilities to both MDD (OR: 1.24, 95 % CI: 1.11–1.38) and DAF (OR: 1.48, 95 % CI: 1.23–1.78) are associated with an increased risk for T2D, while genetic liability to T2D is not associated with the risk for MDD (OR: 1.00, 95 % CI: 0.99–1.01) or DAF (OR: 1.01, 95 % CI: 1.00–1.02). The cross-trait meta-analysis identified 271 genomic loci, of which 29 were novel. Genetic predisposition to MDD and T2D shares six overlapping loci, involving some well-characterized genes, such as <em>TCF4</em> and <em>NEGR1</em>. Colocalization analysis revealed three shared chromosome regions between MDD and T2D, which covers mediator genes including SCYL1, DENND1A, and MAD1L1. Molecular pathway analysis suggests mechanisms that promote the development of T2D through inflammatory pathways overactive in patients with MDD. The SMR analysis and the meta-analysis highlighted seven genes with functional implications for both MDD and T2D, including <em>TNKS2</em>, <em>CCDC92</em>, <em>FADS1</em>, <em>ERI1</em>, <em>THUMPD3</em>, <em>NUCKS1</em>, and <em>PM20D1</em>.</div></div><div><h3>Conclusions</h3><div>Our study points out that depression, in the forms of MDD and DAF, may increase the risk of T2D. Analysis of underlying genetic variation and the molecular pathways, connecting depression and T2D, indicate that the pathophysiological foundations of these two conditions have a notable overlap.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111258"},"PeriodicalIF":5.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016534","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":"Perinatal exposure to methadone or buprenorphine impairs hippocampal-dependent cognition and brain development in juvenile rats","authors":"Arshman S. Sahid ,&nbsp;Melissa J. Bebbington ,&nbsp;Abigail Marcus ,&nbsp;Sarah J. Baracz ,&nbsp;Kelsey S. Zimmermann ,&nbsp;JuLee Oei ,&nbsp;Meredith C. Ward ,&nbsp;Kelly J. Clemens","doi":"10.1016/j.pnpbp.2025.111255","DOIUrl":"10.1016/j.pnpbp.2025.111255","url":null,"abstract":"<div><div>The opioid crisis continues to escalate, disproportionately affecting women of reproductive age. Traditionally the first line of treatment for pregnant women with opioid use disorder is the mu-opioid receptor agonist methadone. However, in recent years, the use of buprenorphine as a replacement therapy has increased as it has fewer side-effects and longer duration of action. Either drug significantly improves outcomes for the mother, but their impact on the developing infant is less certain. To this end, we directly compared the effects of perinatal methadone (MET; 9 mg/kg/day starting dose) versus buprenorphine (BUP; 1 mg/kg/day starting dose) delivered via mini osmotic pump on the long-term behavior of offspring and associated molecular changes in the brain. Opioid exposure across pregnancy resulted in reduced weight gain and smaller litters compared to sham controls, and female pups in particular gained weight at a slower rate across development. Opioid treatment delayed neuromuscular reflex development, with subtle differences observed between MET and BUP. As juveniles, pups with prenatal MET exposure showed poor object recognition, although both MET and BUP have led to deficits in place recognition task. Immunofluorescence studies found corresponding decreases in astrocytes and myelin-positive cells in the hippocampus in both MET and BUP pups. Overall, both MET and BUP were associated with significant developmental and cognitive delays and changes in markers of neuronal development and inflammation, particularly in the hippocampus. The majority of changes were similar between MET and BUP-treated pups, suggesting that gestational exposure to either drug has a similar long-term negative impact on offspring.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111255"},"PeriodicalIF":5.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016528","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":"N, N-dimethyltryptamine (DMT) in rodent brain: Concentrations, distribution, and recent pharmacological data","authors":"Steven A. Barker","doi":"10.1016/j.pnpbp.2025.111259","DOIUrl":"10.1016/j.pnpbp.2025.111259","url":null,"abstract":"<div><div>Renewed interest in the clinical use of psychedelic drugs acknowledges their therapeutic effectiveness. It has also provided a changing frame of reference for older psychedelic drug study data, especially regarding concentrations of <em>N</em>, <em>N</em>-dimethyltryptamine (DMT) reported in rodent brains and recent discoveries in DMT receptor interactions in rat brain neurons and select brain areas. The mode of action of DMT in its newly defined role as a neuroplastogen, its effectiveness in treating neuropsychiatric disorders, and its binding to intracellular sigma-1 and 5HT2a receptors may define these possible roles.</div><div>Recent data also show psychedelics promote neuroplasticity via activation of sigma-1 receptors associated with the endoplasmic reticulum and binding to 5-HT2a receptors predominantly related to the intracellular membrane of the Golgi apparatus in cortical neurons and the failure of DMT to occupy cell surface 5-HT2a receptors. While DMT has been proposed as the endogenous ligand for sigma-1, there is no identified ligand for intracellular 5-HT2a receptors, which serotonin cannot acquire. DMT is proposed to be the missing endogenous ligand.</div><div>These data further suggest that DMT may be involved in brain development in rat pups. Brain levels of DMT have also been shown to be elevated by stress in the rat and appear to be under an inducible, adaptive, physiological regulatory system control. With DMT acting as the natural ligand for intracellular 5HT2a receptors in the Golgi, it may also explain the subjective effects observed from the administration of psychedelics in general and define some of the natural roles for DMT in particular.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111259"},"PeriodicalIF":5.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016535","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 effects of psychostimulants in menstruating women with ADHD – A gender health gap in ADHD treatment?","authors":"Hannelore Findeis,&nbsp;Maria Strauß","doi":"10.1016/j.pnpbp.2025.111261","DOIUrl":"10.1016/j.pnpbp.2025.111261","url":null,"abstract":"<div><h3>Introduction</h3><div>Attention-deficit/hyperactivity disorder is a chronic disorder that begins in childhood and often persists into adulthood. There are clinical observations of a cycle-dependent efficacy of psychostimulants in the treatment of ADHD. This relationship appears to be poorly researched.</div></div><div><h3>Methods</h3><div>A narrative literature review is used to provide an overview of the current state of research and to draw implications for necessary future research.</div></div><div><h3>Results</h3><div>Two studies examined the influence of psychostimulants on female sex hormones in women with ADHD. Another four studies suggested that ADHD symptoms worsen during the luteal phase of the menstrual cycle. Two studies provided a specific intervention tailored to the menstrual cycle.</div></div><div><h3>Discussion</h3><div>Women with ADHD remain understudied and are likely to be mistreated. Investigation of the efficacy of psychostimulants in menstruating women with ADHD seems necessary and long overdue.</div></div><div><h3>Conclusion</h3><div>This highlights the gender health gap in our society and the need for further research to develop an understanding of behavioural and neuroscientific processes in order to adapt treatment strategies for women with ADHD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111261"},"PeriodicalIF":5.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016532","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":"Lower perturbational complexity index after transcranial magnetic stimulation in schizophrenia patients","authors":"Vicente Molina ,&nbsp;Inés Fernández-Linsenbarth ,&nbsp;Rosa Beño-Ruiz- de- la- Sierra ,&nbsp;Emma Osorio-Iriarte ,&nbsp;Alejandro Roig ,&nbsp;Antonio Arjona ,&nbsp;Víctor Rodríguez ,&nbsp;Pablo Núñez ,&nbsp;Jesús Poza ,&nbsp;Alvaro Díez-Revuelta ,&nbsp;Claudia Rodríguez-Valbuena ,&nbsp;Gema Mijancos-Martínez ,&nbsp;Alejandro Bachiller ,&nbsp;Miguel Angel Mañanas","doi":"10.1016/j.pnpbp.2025.111254","DOIUrl":"10.1016/j.pnpbp.2025.111254","url":null,"abstract":"<div><h3>Background</h3><div>Informational integration and differentiation of the cortex can be tested by methods such as the perturbational complexity index (PCI) combined with TMS-induced activity perturbation. The PCI is obtained by stimulating the cortex with TMS and measuring the resulting spatiotemporal cortical responses with high-density EEG.</div></div><div><h3>Methods</h3><div>We have compared PCI between 26 patients with schizophrenia (15 males), 15 of them First Episode (FE) (7 males), and 22 healthy controls (12 males).</div></div><div><h3>Results</h3><div>Values of PCI were significantly lower in patients with schizophrenia, as well as in FE considered alone. There was no significant relation between anomalous self-experiences or symptoms and PCI values in the patients: PCI values were unrelated to treatment doses or illness duration.</div></div><div><h3>Conclusions</h3><div>Our data suggest that spatiotemporal cortical responses to TMS pulses are reduced in patients regarding variability or spatial extension, which could imply a lower capacity for sustaining informational complexity.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111254"},"PeriodicalIF":5.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016527","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":"S1PR3 in hippocampal neurons improves synaptic plasticity and decreases depressive behavior via downregulation of RhoA/ROCK1","authors":"Huiqin Liu ,&nbsp;Shuhua Chen ,&nbsp;Hong Xiang ,&nbsp;Jie Xiao ,&nbsp;Shaoli Zhao ,&nbsp;Xiao Zhang ,&nbsp;Zhihao Shu ,&nbsp;Jing Zhang ,&nbsp;Jie Ouyang ,&nbsp;Quanjun Liu ,&nbsp;Qisheng Quan ,&nbsp;Jianing Fan ,&nbsp;Peng Gao ,&nbsp;Xinru Zheng ,&nbsp;Alex F. Chen ,&nbsp;Hongwei Lu","doi":"10.1016/j.pnpbp.2025.111256","DOIUrl":"10.1016/j.pnpbp.2025.111256","url":null,"abstract":"<div><div>The study investigates how Sphingosine-1-phosphate receptor 3 (S1PR3) and the Chronic Unpredictable Mild Stress (CUMS) affects depression-like behaviors. The S1P/S1PR3 signaling pathway is known to play a role in mood regulation, but it is not yet fully understood how it is connected to depression. This study looks to further explore this topic. To investigate the effect of CUMS on S1PR3 expression in hippocampus neurons and the synaptic plasticity, we observed animals' behavior with Sucrose Preference Test (SPT), Forced Swim Test (FST) and Open Field Test (OFT). Combining molecular and histological analysis, we investigated the S1PR3 expression, the change in synapse density, and synaptic structure change in the hippocampus. The CUMS caused a significant decrease in the S1PR3 expression, the density of the synaptic spine and synaptic ultrastructure change in mice. On the other hand, over-expression of S1PR3 by adeno-associated virus (AAV) in hippocampal neurons alleviated the depressive-like behaviors and synaptic deficits observed in stress-susceptible animals. Furthermore, the depressive-like phenotype and synaptic impairments were normalized by the expression of RhoA, implicating the RhoA/ROCK1 pathway in S1PR3 actions. Collectively, our findings provide strong evidence that S1PR3 plays a key role in hippocampal synaptic plasticity and depression and that modulation of S1PR3/RhoA/ROCK1 signaling may offer a novel therapeutic strategy for MDD. This study not only underscores the therapeutic potential of S1PR3 but also provides novel insights into the molecular mechanisms underlying depression.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111256"},"PeriodicalIF":5.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016529","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}