Behavioral and Brain Functions最新文献

{"title":"The impact of paternal PTSD-like stress on cognitive behavior and hippocampal BDNF expression in adolescent male and female rat offspring: modulatory effects of lithium.","authors":"Zahra Ebrahimkhani, Hamidreza Behnoud, Ameneh-Sadat Kazemi, Batool Ghorbani Yekta","doi":"10.1186/s12993-026-00324-2","DOIUrl":"10.1186/s12993-026-00324-2","url":null,"abstract":"<p><p>Prenatal stress may lead to cognitive and behavioral dysfunction in the offspring. Large evidence has shown the deleterious effects of maternal stress on cognitive and behavioral functions of the offspring; however, the effect of paternal stress has not been well documented. In the present study, we aimed to investigate the effect of paternal stress (chronic electrical footshocks, post-traumatic stress disorder or PTSD-like model) on cognitive and behavioral functions, and brain-derived neurotrophic factor (BDNF) hippocampal level in both male and female offspring during adolescence. The father rat (stress-exposed) was exposed to three consecutive shocks in a fear conditioning apparatus for ten times during four weeks, in an uncertain and unpredictable schedule. Saline (0.5 mL) or lithium chloride (50 mg/kg) was intraperitoneally injected to male and female offspring during 21-41 postnatal day (PND). The results showed that paternal stress decreased locomotor activity in female offspring, and increased anxiety-like behavior in both male and female offspring, with more effect on females. Paternal stress also decreased pain subthreshold only in female offspring and impaired passive avoidance and spatial memory in both male and female offspring. Paternal stress also decreased BDNF expression level only in female offspring. However, lithium reversed most of the behavioral dysfunctions in rats' offspring with a history of paternal stress. We concluded that paternal stress significantly impairs cognitive and behavioral function in the offspring during adolescence, with more effect on females. Also, chronic lithium treatment may reverse the deleterious effects of paternal stress.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neural, neurotransmitter, and transcriptomic mechanisms underlying dispositional greed: exploring its link to negative psychopathology.","authors":"Lei Feng, Ying Hu, Xiang Li, Chang Liu, Yue Ge, Pinchun Wang, Weipeng Jin, Huibin Chang, Qiang Wang","doi":"10.1186/s12993-026-00328-y","DOIUrl":"10.1186/s12993-026-00328-y","url":null,"abstract":"","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of high-fat diet and feeding time on daily anxious-like behaviors in aged male rats.","authors":"Athena Rivera, Ellie Thorstenson, M Behnam Ghasemzadeh, Deanna M Arble","doi":"10.1186/s12993-026-00326-0","DOIUrl":"10.1186/s12993-026-00326-0","url":null,"abstract":"<p><p>Anxiety symptoms exhibit day-night variation, often peaking in the late afternoon or evening. Despite clinical recognition of anxiety's diurnal variation, time of day is rarely considered in the design or interpretation of anxiety research. In this study, we used aged (10-12 month) Long-Evans male rats to examine the extent in which time of day, chronic (> 15 weeks) high-fat diet feeding, and time-restricted feeding affect anxious-like behaviors in the elevated plus maze and the novelty box test. We find that anxious-like behaviors, such as closed-arm entries, are consistently higher during the animal's inactive phase. This day-night variation was unaffected by high-fat diet feeding. Interestingly, restricting food to a 12-hour window did not invert the day-night variation in anxiety but reduced anxious-like behavior overall. These findings underscore the importance of multiple testing times when measuring anxiety and illustrate the relative resiliency of daily patterns in anxiety expression. Overall, we conclude that time of day modulates anxious-like behavior and should be considered in experimental designs and therapeutic interventions for anxiety.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A brainstem-thalamocortical circuit mediates postoperative pain duration induced by sleep deprivation.","authors":"Lei Li, Huijie Zhang, Yinxiu Gao, Suliman Khan, Fengling Wu, Xiuhua Ren, Jingjing Zhang, Kelil Haji Bedane, Liguo Jian, Weidong Zang, Qian Bai, Jing Cao","doi":"10.1186/s12993-026-00325-1","DOIUrl":"10.1186/s12993-026-00325-1","url":null,"abstract":"<p><strong>Background: </strong>Postoperative sleep disturbances are common and have been shown to exacerbate incisional pain by enhancing the central nervous system's excitability. However, the specific neural circuit mechanisms underlying the pain chronification induced by postoperative sleep deprivation remain largely elusive.</p><p><strong>Methods: </strong>We established a model of postoperative pain by plantar incision with perioperative sleep deprivation 6 h/day for 3 consecutive days in male mice. The activity of the neurons in the paraventricular thalamus nucleus (PVT) and the locus coeruleus (LC) was assessed using immunofluorescence and fiber photometry. Viral tracing, immunofluorescence staining, chemogenetics, optogenetics, and fiber photometry were utilized to investigate the anatomical and functional connections of the neural circuit. Furthermore, chemogenetic and optogenetic manipulations, combined with behavioral tests, were employed to investigate the roles of various nuclei or neural circuits in the perioperative sleep deprivation-induced prolongation of postsurgical pain.</p><p><strong>Results: </strong>Sleep deprivation prolonged the duration of postsurgical pain and increased the excitability of glutamatergic neurons in the PVT (PVT^Glu) and tyrosine hydroxylase-positive neurons in the LC (LC^TH). Viral tracing revealed a direct projection from LC^TH neurons to PVT^Glu neurons. Selective chemogenetic activation of the LC^TH-PVT^Glu pathway reduced sleep duration and replicated the pain-prolonging effects of sleep deprivation. Furthermore, viral tracing and morphology indicate that GABAergic neurons in the medial prefrontal cortex (mPFC^GABA) receive projections from the LC^TH-PVT^Glu pathway. We found that hypersensitivity was sustained by the activation of the LC^TH-PVT^Glu-mPFC after incision, while its chemogenetic inhibition reversed sleep deprivation mediated pain prolongation.</p><p><strong>Conclusion: </strong>These findings indicate that brainstem-thalamocortical pathway mediates the sleep deprivation-induced prolongation of postoperative pain. This circuit may serve as a mechanistic link between disrupted arousal states and pain duration, representing a potential therapeutic target for managing postsurgical pain.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of the kynurenine pathway in conditioned place aversion induced by synthetic cannabinoid CP-55940.","authors":"Jin Cong, Hang Zhang, Ningjing Li, Jun Yang, Meilin Liu, Qingjie Ma, Chuanying Zhang, Guiming Yan","doi":"10.1186/s12993-026-00327-z","DOIUrl":"10.1186/s12993-026-00327-z","url":null,"abstract":"<p><p>BACKGROUND: The therapeutic potential of cannabinoids is increasingly recognized; however, their use is often associated with adverse effects, such as conditioned place aversion (CPA). The molecular mechanisms underlying CPA remain poorly understood, particularly the role of the kynurenine pathway (KP) and its interaction with cannabinoid receptors. This study aimed to elucidate these mechanisms, focusing on the synthetic. METHODS: We employed a mouse conditioned place preference behavioral model to assess CPA following the administration of CP-55940 at a dosage of 1 mg/kg via intraperitoneal injection. We conducted a comprehensive analysis of key metabolites in the kynurenine pathway, specifically measuring levels of kynurenic acid (KYNA) in the hippocampus, while also monitoring quinolinic acid levels for comparison. Additionally, we utilized pharmacological inhibition of KATII with PF-04859989 to further explore KYNA’s role in mediating CPA. RESULTS: Our findings revealed significant increases in tryptophan, kynurenine, and KYNA levels in the hippocampus following administration of CP-55940, whereas quinolinic acid levels remained unchanged. Notably, pharmacological inhibition of KATII effectively reduced CPA, thereby affirming the critical role of KYNA in the aversive response. Furthermore, we observed that KYNA downregulated CB1 receptor (CB1R) expression, which was restored upon inhibition of KYNA synthesis. Additionally, G protein-coupled receptor 35 (GPR35) expression was significantly reduced in the CPA model, and its levels were positively correlated with KYNA, suggesting intricate molecular interactions. CONCLUSION: This study elucidates the complex interplay between KYNA, CB1R, and GPR35 in the context of cannabinoid-induced CPA, highlighting the pivotal role of the TRP–KYN pathway in mediating adverse behavioral effects associated with cannabinoids. These findings open avenues for the development of therapeutic targets aimed at mitigating such effects. Future research should focus on validating these results through gene knockout models and further exploring the clinical implications of KYNA modulation in cannabinoid pharmacology and neuropsychiatric disorders. </p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive training in neurological disorders: meta-analytic evidence for behavioral gains and neural correlates.","authors":"Geng Li, Yang Liu, Chengzhen Liu, Yihan Zhang","doi":"10.1186/s12993-026-00323-3","DOIUrl":"10.1186/s12993-026-00323-3","url":null,"abstract":"<p><p>BACKGROUND: Cognitive decline in neurological disorders substantially impairs daily functioning and quality of life, underscoring the need for effective non-pharmacological interventions. We aimed to quantify the behavioral benefits of cognitive training, characterize convergent patterns of task-related brain activation changes, and examine moderators of the neural responses underlying training effects. METHODS: We conducted a meta-analysis of 21 task-based neuroimaging studies. Behavioral outcomes were synthesized using multivariate meta-analysis, while neural changes were examined with seed-based d mapping (SDM) to identify spatially consistent activation differences between training and control groups. Moderator analyses evaluated training parameters, study designs, and participant characteristics, and brain–behavior associations were assessed to link regional activation changes with cognitive improvements. RESULTS: Cognitive training produced a significant, moderate improvement in cognitive task performance (Hedges’ g = 0.451, 95% CI 0.207–0.696; p < .001). Neuroimaging meta-analysis showed increased task-evoked activation after training in the bilateral precuneus and the left precentral gyrus (L. PreCG) relative to controls. Only precuneus activation increases were associated with behavioral gains. Moderator analyses indicated reduced precuneus activation but increased L. PreCG activation during transfer relative to trained tasks, and reduced L. PreCG activation for adaptive versus fixed-difficulty training. Passive controls also showed stronger L. PreCG activation changes than active controls, whereas participant characteristics and training dose showed no significant effects. CONCLUSIONS: Cognitive training improved cognitive task performance and was accompanied by a convergent activation signature centered on the bilateral precuneus and the L. PreCG in neurological disorders. Precuneus engagement tracked cognitive gains, highlighting it as a candidate neural marker of training-related plasticity in this population. </p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of predator stress on electroshock seizure threshold: insights into GABAergic, glutamatergic, and serotonergic pathways in mice.","authors":"Ali Vafaei, Mohammad Amin Kharaghani, Amirhossein Shahsavand, Razieh Mohammad Jafari, Hamed Shafaroodi, Mehdi Ghasemi, Ahmad Reza Dehpour","doi":"10.1186/s12993-026-00321-5","DOIUrl":"10.1186/s12993-026-00321-5","url":null,"abstract":"<p><strong>Background: </strong>Post-traumatic stress disorder (PTSD) disrupts neural pathways, increasing susceptibility to neurological disorders, including epilepsy. Stress-induced alterations in glutamatergic, GABAergic, and serotonergic systems influence seizure susceptibility. This study investigates seizure thresholds within a PTSD-relevant mouse model, evaluating the roles of these neurotransmitters.</p><p><strong>Methods: </strong>Male NMRI mice were exposed to predator stress using Wistar rats. Seizure thresholds were assessed via electroshock tests at multiple post-stress intervals. Pharmacological interventions, diazepam, MK-801, and fluoxetine, were administered seven days post-stress. Hippocampal tissues were analyzed for GABA_A receptor α₁ subunit, NMDAR1, and 5-HT_1A receptor expression, as well as nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and extracellular signal-regulated kinase (ERK) protein levels, utilizing Western blot techniques.</p><p><strong>Results: </strong>Predator stress significantly decreased seizure thresholds in a time-dependent manner, with the highest effect on day 7 (P < 0.0001). Treatment with diazepam (P < 0.05), MK-801 (P < 0.0001), and fluoxetine (P < 0.0001) reversed these effects, increasing seizure thresholds. Western blot analysis revealed reduced expression of GABA_Aα₁, NMDAR1, and 5-HT_1A receptors (P < 0.001). Additionally, NF-κB levels were elevated while ERK levels were reduced (P < 0.001).</p><p><strong>Conclusion: </strong>This study shows that predator stress is associated with increased seizure susceptibility and with downregulation of hippocampal GABAAα1R and 5-HT1AR expression, together with enhanced NF-κB activation and reduced ERK signaling. Pharmacological modulation of GABAergic, glutamatergic, and serotonergic pathways reversed the stress-induced reduction in seizure threshold in this model, suggesting that these systems may contribute to stress-related seizure susceptibility.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13011472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating interbrain synchrony under teamwork disruption: an fNIRS hyperscanning study.","authors":"Coralie Réveillé, Grégoire Vergotte, Gérard Dray, Pierre-Antoine Jean, Pierre Jean, Simon Pla, Stephane Perrey, Grégoire Bosselut","doi":"10.1186/s12993-026-00320-6","DOIUrl":"10.1186/s12993-026-00320-6","url":null,"abstract":"<p><strong>Background: </strong>Teams are inherently adaptive entities that continuously adapt to changes or disruptions in their tasks or environments. During collaboration, interbrain synchrony (IBS) emerges, reflecting the temporal alignment of neural activity between team members. Building on this, IBS has been proposed as a potential marker of teamwork, suggesting that IBS should be sensitive to changes in teamwork.</p><p><strong>Purpose: </strong>The present study investigated whether IBS is sensitive to changes in teamwork. We hypothesized that disruptions in teamwork would be accompanied by alterations in IBS dynamics.</p><p><strong>Methods: </strong>Ninety-eight healthy adults (mean age = 22.5 ± 3.22 years; 69 females, 65.1%) were assigned to forty-nine dyads. Each pair completed a 20-minute computer-based navigation task while their brain activity was simultaneously recorded using fNIRS hyperscanning. Dyads in the experimental group encountered an unexpected increase in task difficulty midway through the task, whereas those in the control group completed the task without disruption. We examined three features of IBS - its overall level, temporal slope trajectory, and the temporal recurrence patterns.</p><p><strong>Results: </strong>Control analyses confirmed that IBS reliably emerged during the task (χ²(1) = 50.24, p < .001) and that the experimental manipulation successfully disrupted teamwork, as reflected in altered team behavioral responses in communication (χ²(1) = 8.48, p = 0.004) and performance (χ²(1) = 24.99, p < .001). Nevertheless, no evidence was found for disruption-related changes in IBS across the three features examined (all Time x Group interactions p > .05.</p><p><strong>Conclusion: </strong>These findings raise the possibility that IBS may reflect a stable collective state rather than a reactive one, thereby challenging its interpretation as a direct marker of teamwork. Methodological considerations, including the operationalization of IBS, are also discussed as potential explanations for the lack of observed change in IBS.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12977408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of electroacupuncture at Zusanli on pain-perception-related brain nuclei in KOA mice: a study on cortical and subcortical c-fos expression.","authors":"Aiwen Chen, Tiantian Zhao, Xiaofei Gao, Huazheng Liang, Lize Xiong, Weidong Shen","doi":"10.1186/s12993-026-00322-4","DOIUrl":"10.1186/s12993-026-00322-4","url":null,"abstract":"<p><strong>Background: </strong>Electroacupuncture is widely accepted to treat pain related conditions, but detailed mechanisms remain unknown.</p><p><strong>Objective: </strong>To explore cortical and subcortical subnuclei involved in electroacupuncture stimulation (EAS) analgesia by observing EAS's analgesic efficacy and c-fos expression changes, providing a basis for neural circuit research and clinical transcranial magnetic stimulation (TMS) therapy.</p><p><strong>Design, setting, participants and interventions: </strong>A chronic inflammatory pain model was established using knee osteoarthritis (KOA). Bilateral Zusanli was selected for electroacupuncture intervention. Von Frey test, open field test, elevated plus maze, and tail suspension test, and immunohistochemical staining were performed.</p><p><strong>Main outcomes measures: </strong>Changes in mechanical pain threshold and pain-related emotional behaviors and distribution of c-fos positive cells in cortical and subcortical nuclei.</p><p><strong>Results: </strong>Electroacupuncture significantly increased mechanical pain thresholds in KOA model mice. KOA modeling caused c-fos downregulation in the motor cortex, insular cortex, secondary auditory cortex, dorsal peduncular cortex, temporal association cortex, caudate putamen, lateral septal nucleus, accumbens nucleus, and the anterior cortical amygdaloid area. Electroacupuncture at Zusanli reversed these changes, upregulating c-fos in abovementioned brain regions, and additionally upregulated c-fos expression in the granular insular cortex, extended amydala.</p><p><strong>Conclusion: </strong>Inflammatory pain induces widespread inhibition of neuronal activity in cortical and subcortical nuclei. The core mechanisms of electroacupuncture analgesia may involve direct reversal of abnormal inhibition in the lateral septal nucleus, caudate putamen, accumbens nucleus, and the anterior cortical amygdaloid area and activation of the granular insular cortex, medial septal nucleus and the extended amygdala for pain information integration.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overexpression of FoxO3a in the dentate gyrus alleviates CUS-induced anxiety- and depression-like behaviors and cognitive impairment.","authors":"Shanyong Yi, Bin Yang, Xianxian Zhang, Bin Zhao, Lai Wei, Zhijun Yao, Ruiling Zhang","doi":"10.1186/s12993-026-00319-z","DOIUrl":"10.1186/s12993-026-00319-z","url":null,"abstract":"<p><strong>Background: </strong>Excessive stress leads to injury and dysfunction, but the underlying mechanism remains unclear. As a human longevity gene, forkhead box O3a (FoxO3a) is a transcription factor that regulates various cellular processes, including the response to oxidative stress, apoptosis, and autophagy. This study aims to explore whether FoxO3a in the dentate gyrus (DG) of the hippocampus is involved in the formation of anxiety- and depressive-like behavior and cognitive impairment in stressed rats and to investigate the detailed mechanism.</p><p><strong>Methods: </strong>This study was conducted using the 6-week chronic unpredictable stress (CUS) model. Before the stress treatment, we injected an adeno-associated virus (AAV) vector to overexpress FoxO3a specifically in the DG. Following the 6-week CUS treatment, a series of behavioral tests was conducted. Depression-like behavior was assessed using the sucrose preference test (SPT) and the open field test (OFT). The state of desperation was assessed with the forced swim test (FST) and tail suspension test (TST). Anxiety-like behavior was measured in the elevated plus maze (EPM) and OFT. Cognitive function was examined using the Y-maze test (Y-maze), novel object recognition test (NORT), and Morris water maze test (MWM). The level of reactive oxygen species (ROS) and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured. The levels of inflammatory factors were detected by ELISA. Pathological injury in DG was observed using thionine staining. The expression levels of FoxO3a, brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD95), synaptophysin (SYN), and proliferation marker Ki67 (Ki67) were determined using western blot.</p><p><strong>Results: </strong>CUS leads to various abnormal changes, including anxiety- and depressive-like behavior, cognitive impairment, oxidative stress, neuroinflammation, neuropathological alterations in the DG, and decreased expression of FoxO3a, BDNF, PSD95, SYN, and Ki67. All these abnormal changes were significantly alleviated by targeted AAV-FoxO3a injection in the DG.</p><p><strong>Conclusions: </strong>In conclusion, our study demonstrates that the downregulation of FoxO3a induced by CUS in the DG triggers oxidative stress and inflammatory response, inhibits cell proliferation, and induces abnormal synaptic plasticity, ultimately leading to anxiety- and depressive-like behaviors and cognitive impairment.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12977563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}