Neurobiology of Stress最新文献

{"title":"Regulation of behavioral responses to single prolonged stress in male and female rats: Role of PACAP","authors":"Marissa A. Smail ,&nbsp;Evelin M. Cotella ,&nbsp;Susan E. Martelle ,&nbsp;James B. Chambers ,&nbsp;Ria K. Parikh ,&nbsp;Christine E. Moore ,&nbsp;Ben A. Packard ,&nbsp;Nawshaba Nawreen ,&nbsp;Rachel D. Moloney ,&nbsp;James P. Herman","doi":"10.1016/j.ynstr.2025.100727","DOIUrl":"10.1016/j.ynstr.2025.100727","url":null,"abstract":"<div><div>Post-Traumatic Stress Disorder (PTSD) is a debilitating condition in which a traumatic experience triggers symptoms related to re-experiencing, avoidance, arousal, and mood dysregulation. PTSD negatively impacts 6 % of people during their lifetime, with women being disproportionally affected and exhibiting different, more severe symptoms than men. Despite this widespread impact, the molecular mechanisms underlying PTSD and its sex differences remain poorly understood. Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is a neuropeptide which participates in fine-tuning circuitry throughout the brain and has been associated with PTSD in humans, especially in women. Here, we use Single Prolonged Stress (SPS), an animal model of PTSD, to explore the roles of PACAP and sex in PTSD-like behaviors. Specifically, a PACAP agonist or antagonist was infused into the infralimbic (IL) prefrontal cortex, a region key to regulating fear- and anxiety-related behaviors, prior to SPS in male and female rats. Rats were then tested in open field/novel object, elevated plus maze, and social interaction. Utilizing a behavioral indexing method, we were able to uncover SPS effects in PTSD-related behavioral domains that were differentially impacted by PACAP manipulations in males and females. While both sexes exhibited increased threat avoidance and decreased threat assessment following SPS, females increased sociability while males decreased sociability. Males also appeared to be protected by IL PACAP antagonism while female SPS phenotypes were exacerbated by IL PACAP agonism. Furthermore, RNAscope revealed that PACAP in the prefrontal cortex responds differently to SPS in males and females. Together, these findings suggest complex relationships between SPS, sex, and IL PACAP which may have important implications for treating PTSD in men and women.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100727"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921567","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":"Dynamics of stress-induced c-fos expression in the rat prelimbic cortex: lessons from intronic and mature RNA and protein analyses","authors":"Patricia Molina ,&nbsp;Xavier Belda ,&nbsp;Sandra Beriain ,&nbsp;Sara Serrano ,&nbsp;Gentzane Compte ,&nbsp;Raül Andero ,&nbsp;Antonio Armario","doi":"10.1016/j.ynstr.2025.100729","DOIUrl":"10.1016/j.ynstr.2025.100729","url":null,"abstract":"<div><div>Despite the extensive use of <em>c-fos</em> as a marker of stress-induced neuronal activation, key aspects regarding its dynamics of expression remain poorly characterized. In the present study, we assessed in the prelimbic cortex of adult male rats the immediate transcriptional response of <em>c-fos</em> by measuring the heteronuclear (hn)RNA and mature (m)RNA expression by double fluorescent <em>in situ</em> hybridization as well as the c-Fos protein using immunofluorescence (FOS). We quantified in three different experiments the number of <em>c-fos</em> hnRNA+, mRNA+ and FOS+ neurons under basal conditions, immediately after different periods of immobilization stress (IMO), and after a recovery period. Our results indicate that stress induced a large increase in the number of positive neurons for all markers analyzed, each displaying a different time course. Moreover, our findings indicate that measuring the intensity of signal per neuron also provides relevant information. In addition, we report an increased number of FOS+ neurons after only 8–15 min of IMO, suggesting a surprisingly fast initiation of protein translation. Finally, the maturation from <em>c-fos</em> hnRNA+ to mRNA+ might depend on the duration and/or intensity of stress-induced activation. Our findings contribute to a better understanding of the dynamics of stress-induced <em>c-fos</em> expression and underscore the importance of examining multiple molecular components when using <em>c-fos</em> as a proxy of neuronal activation.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100729"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900049","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":"Sex-dependent impact of parental verbal abuse on brain lateralization of language","authors":"Xingzhen Wang ,&nbsp;Jiaojian Wang ,&nbsp;Zhenglong Lin ,&nbsp;Yang Yang ,&nbsp;Min Xu","doi":"10.1016/j.ynstr.2025.100730","DOIUrl":"10.1016/j.ynstr.2025.100730","url":null,"abstract":"<div><h3>Background</h3><div>Child maltreatment profoundly impacts mental health and cognitive abilities, with effects varying according to the type of maltreatment. Parental verbal abuse (PVA) is a pervasive yet often overlooked form of child maltreatment linked to significant changes in brain structures crucial for language. This study investigated the impact of PVA on behavior, brain structure, and function related to language, examining how these effects may differ between females and males.</div></div><div><h3>Methods</h3><div>We recruited 142 adults who experienced varying levels of PVA during childhood. Participants completed questionnaires to assess their exposure to PVA, nonverbal abuse and neglect, and underwent cognitive tests to evaluate their language-related skills. We employed diffusion tensor imaging and functional magnetic resonance imaging to explore how PVA affect structural characteristics of the arcuate fasciculus (AF) and brain activation patterns during a sentence comprehension task.</div></div><div><h3>Results</h3><div>Hierarchical regressions revealed sex-dependent effects of PVA on the AF lateralization. In females, PVA exposure was associated with decreased leftward lateralization of the AF’s anterior segment and reduced frontal lateralization during sentence comprehension. Conversely, in males, PVA was related to increased leftward lateralization of the same segment, but this structural change did not correspond with significant effects on functional lateralization or language performance.</div></div><div><h3>Conclusions</h3><div>This study highlights the susceptibility of AF’s anterior segment and frontal activation to PVA, revealing distinct patterns between females and males. The findings underscore the necessity for future research to address these sex differences and develop targeted interventions to meet the distinct challenges that females and males may face.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100730"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907874","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":"Can the gut-brain axis provide insight into psilocybin's therapeutic value in reducing stress?","authors":"Alanna Kit ,&nbsp;Kate Conway ,&nbsp;Savannah Makarowski ,&nbsp;Grace O'Regan ,&nbsp;Josh Allen ,&nbsp;Sandy R. Shultz ,&nbsp;Tamara S. Bodnar ,&nbsp;Brian R. Christie","doi":"10.1016/j.ynstr.2025.100732","DOIUrl":"10.1016/j.ynstr.2025.100732","url":null,"abstract":"<div><div>There is growing interest in exploring the therapeutic potential and mechanisms of action of psilocybin on stress-related neuropsychiatric disorders, including depression, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), addiction, and disordered eating. Despite promising progressions in preclinical and clinical research, the neurobiological and physiological mechanisms underlying the therapeutic effects of psilocybin remain complex, involving multiple systems with numerous homeostatic feedback signaling pathways throughout the body. This review paper explores how psilocybin mechanistically interacts with the gut microbiota, enteric nervous system, hypothalamic-pituitary axis, and how psilocybin influences the bidirectional communication between peripheral and neuronal systems. Shifting towards a more integrated paradigm to unravel the mechanisms through which psilocybin affects the bidirectional gut-brain axis holds the promise of significantly advancing our understanding of psilocybin-based therapies from preparation of treatment, administration, to proceeding long-term integration. Such an understanding can extend beyond the treatment of psychiatric disorders, further encompassing a broader spectrum of inflammatory-related disorders.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100732"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125196","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":"Aggression as a contributing factor to social defeat and stress vulnerability","authors":"Megan M. John ,&nbsp;Melissa A. Pratt ,&nbsp;Jazmine D.W. Yaeger ,&nbsp;Renée A. Brummels ,&nbsp;Leighton J. Ledesma ,&nbsp;Lauren S. Meyer ,&nbsp;RaeAnn L. Hartwig ,&nbsp;Gabriel L. Legner ,&nbsp;Nathan G. Gilbertson ,&nbsp;Patrick J. Ronan ,&nbsp;Cliff H. Summers","doi":"10.1016/j.ynstr.2025.100728","DOIUrl":"10.1016/j.ynstr.2025.100728","url":null,"abstract":"<div><div>The Stress Alternatives Model (SAM) is a social defeat/avoidance paradigm developed in our lab that reveals evolutionarily conserved escape responses in fish, hamsters, rats, and mice. During social interactions in a neutral arena, available escape routes sized exclusively for smaller test animals allow for avoidance of a social aggressor. This 4-day social interaction protocol pairs C57BL/6N test mice and a larger, novel, aggressive CD1 mouse each day. Although escape portals are available, and the CD1 aggressor is unremittingly antagonistic, only half of the mice tested utilize the escape tunnels, while escape latency dramatically decreases over time in mice that escape. We sought to determine whether aggression provided the trigger of two stress-related phenotypes that are produced by the SAM. The results suggest threat of aggression, determined by the first attack, is necessary for phenotype development, but the intensity of aggression over time does not determine which phenotype is chosen. Phenotypes are determined by responsiveness and counterbalanced neurocircuits that promote stress-resilience or vulnerability. These stress neurocircuits are modulated by orexins, through orexin 1 and 2 receptors (Orx₁, Orx₂), which promote pro-stress behaviors. In the primary pro-stress neurocircuitry of the aBLA, we examined Akt and mToR gene expression in stress-resilient (Escape) and -vulnerable (Stay) mice. The quantity of <em>Hcrtr</em>_<em>1</em> mRNA/cell was elevated in Stay mice, as were the mRNA/cell numbers for <em>Mtor</em>. However, the increase of <em>Akt</em>_<em>2</em> and <em>Mtor</em> mRNA/cell was not evident specifically in <em>Hcrtr</em>_<em>1</em> expressing cells, suggesting these molecular markers of neuroplasticity are not being activated by Orx₁ receptors.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100728"},"PeriodicalIF":4.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881739","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":"Early-life adversities compromise behavioral development in male and female mice heterozygous for CNTNAP2","authors":"Gabriele Chelini ,&nbsp;Tommaso Fortunato-Asquini ,&nbsp;Enrica Cerilli ,&nbsp;Katia Monsorno ,&nbsp;Benedetta Catena ,&nbsp;Ginevra Matilde Dall’O’ ,&nbsp;Rosa Chiara Paolicelli ,&nbsp;Yuri Bozzi","doi":"10.1016/j.ynstr.2025.100726","DOIUrl":"10.1016/j.ynstr.2025.100726","url":null,"abstract":"<div><div>The etiological complexity of psychiatric disorders arises from the dynamic interplay between genetic and environmental vulnerabilities. Among the environmental components, early-life adversities are a major risk factor for developing a psychiatric condition. Yet, the interaction between adversities early in life and genetic vulnerability contributing to psychopathology is poorly understood. To fill this gap, we took advantage of the ideally controlled conditions of a pre-clinical approach. We raised a mouse model with genetic predisposition for multiple psychiatric disorders (autism spectrum, schizophrenia, bipolar disorder), the <em>Cntnap2</em>^{<em>+/−</em>} mouse, with limited bedding and nesting (LBN), a well-established paradigm to induce early-life stress in rodents. These mice were compared to LBN-raised <em>Cntnap2</em>^<em>+/+</em> littermates, as well as parallel groups of <em>Cntnap2</em>^<em>+/+</em> and <em>Cntnap2</em>^{<em>+/−</em>} raised in standard conditions. Using a battery for behavioral phenotyping we show that early-life adverse experience shapes non-overlapping phenotypic landscapes based on genetic predisposition. Specifically, LBN-raised <em>Cntnap2</em>^{<em>+/−</em>} mice displayed a perseverative risk-taking behavior in the elevated plus maze. Interestingly, this trait was highly predictive of their success in social interaction, suggesting that the intrusion of anxiety into the social behavioral domain may contribute to extreme gain- or loss-of function in sociability. Finally, we show that LBN promotes hypertrophy of post-synaptic densities in the basolateral nucleus of the amygdala (BLA), but only in <em>Cntnap2</em>^{<em>+/−</em>} raised in LBN this is associated with microglia abnormalities. We conclude that the interplay between early-life adversities and <em>Cntnap2</em> haploinsufficiency alters emotion regulation in mice, putatively as a consequence of deficient synaptic scaling in the BLA.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100726"},"PeriodicalIF":4.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876793","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":"Building a social brain: Cells, circuits and behavior across the lifespan","authors":"Maya Opendak","doi":"10.1016/j.ynstr.2025.100725","DOIUrl":"10.1016/j.ynstr.2025.100725","url":null,"abstract":"<div><div>Disrupted social behavior is a fundamental indicator of compromised mental health, such as anxiety and depression, and serves as an early diagnostic marker for disorders that can develop later in life. However, our understanding of how the neural circuits for social behavior develop and how environmental disturbances at various developmental stages affect infant behavior is limited. Through my research with rats, I have established a foundation for identifying specific neuroanatomical circuits in infants that produce age-appropriate social behavior and how these systems may change in response to adversity. Overall, these studies have helped generate technical and conceptual advances in our understanding of social development and early life stress. These studies have employed multiple levels of analysis and functional brain dissection to identify novel targets of early social stress and measure how the infant brain responds to social information in typical and perturbed development.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100725"},"PeriodicalIF":4.3,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834121","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":"An inverted U-shaped relationship between chronic stress and the motivation to expend effort for reward","authors":"Wei Yi ,&nbsp;Xin Li ,&nbsp;Wangxiao Chen ,&nbsp;Linlin Yan ,&nbsp;Fei Xin ,&nbsp;Tony W. Buchanan ,&nbsp;Jianhui Wu","doi":"10.1016/j.ynstr.2025.100724","DOIUrl":"10.1016/j.ynstr.2025.100724","url":null,"abstract":"<div><div>Dysfunction in the motivation to expend effort for reward is considered a crucial symptom of stress-related mental illness. Few studies have explored the relationship between chronic stress and the motivation to exert effort for reward, along with its underlying neural mechanisms. We investigated this relationship in ninety undergraduates who were undergoing a chronic stressor: preparing for the National Postgraduate Entrance Examination (NPEE). Students engaged in an effort-reward task while EEG signals were recorded, wherein they could accept or reject an offer to expend effort for another opportunity to obtain the reward. Participants’ chronic stress levels were assessed using the Perceived Stress Scale (PSS) and their decision was further captured by a drift-diffusion model (DDM). Compared to reward omission, reward delivery led to increased amplitude of the reward positivity (RewP) ERP waveform, particularly in extra reward trials relative to regular trials. Importantly, the PSS score showed an inverted U-shaped relationship with the motivation indicators, including offer acceptance rate (behavioral index), drift rate (model parameter), and ΔRewP (i.e., the difference in RewP in response to reward delivery compared to reward omission, ERP component). These findings suggest an inverted U-shaped relationship between chronic stress and motivation, suggesting that individuals display diminished motivation when exposed to low or high levels, relative to moderate levels, of chronic stress. Our study holds significant implications for understanding both vulnerability and resilience to stress-related mental disorders.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100724"},"PeriodicalIF":4.3,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777062","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 insular cortex-nucleus tractus solitarius glutamatergic pathway involved in acute stress-induced gastric mucosal damage in rats","authors":"Zepeng Wang ,&nbsp;Xinyu Li ,&nbsp;Yuanyuan Li ,&nbsp;Xuehan Sun ,&nbsp;Yuxue Wang ,&nbsp;Tong Lu ,&nbsp;Dongqin Zhao ,&nbsp;Xiaoli Ma ,&nbsp;Haiji Sun","doi":"10.1016/j.ynstr.2025.100723","DOIUrl":"10.1016/j.ynstr.2025.100723","url":null,"abstract":"<div><div>Previous studies have shown that acute stress-induced gastric mucosal damage is linked to excessive activation of parasympathetic nervous system. The Insular Cortex (IC), the higher centers of the parasympathetic nervous system, serves as both the integration site of gastric sensory information and play a crucial role in the regulation of gastric function. However, whether the IC is involved in Restraint water-immersion stress (RWIS)-induced gastric mucosal damage has not been reported. In this study, we examined the expression of neuronal c-Fos, PSD95 and SYN-1 protein expression in IC during RWIS by immunofluorescence and western blot techniques, as well as assessed IC blood oxygenation level dependant (BOLD) through functional MRI. Chemical genetics techniques specifically modulate the activity of IC glutamatergic neurons and IC-nucleus tractus solitary (NTS) glutamatergic pathway to elucidate their contributions to RWIS-induced gastric mucosal damage. The results showed that the expression of c-Fos, PSD95, and SYN-1 protein in IC increased significantly after RWIS, along with a noticeable enhancement in fMRI signal intensity. Furthermore, inhibiting IC glutamatergic neurons and the IC-NTS glutamatergic neural pathway resulted in a significant reduction in gastric mucosal damage, an increase in the expression of Occludin, Claudin-1, and PCNA in the gastric wall, while the expression of nNOS decreased and CHAT increased. These findings suggest that during RWIS, IC glutaminergic neurons are activated, promoting stress-induced gastric mucosal damage through the IC-NTS-vagal nerve pathway.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100723"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768513","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":"Dynamic changes of serotonin transporter expression in the prefrontal cortex evoked by aggressive social interactions","authors":"Huba Szebik ,&nbsp;Christina Miskolczi ,&nbsp;Bíborka Bruzsik ,&nbsp;Gyula Balla ,&nbsp;Soma Szabó ,&nbsp;László Biró ,&nbsp;Éva Mikics","doi":"10.1016/j.ynstr.2025.100722","DOIUrl":"10.1016/j.ynstr.2025.100722","url":null,"abstract":"<div><div>Aggression is a complex behavior influenced by developmental experiences, internal state, and social context, yet its neurobiological underpinnings remain insufficiently understood. The serotonergic system, particularly the serotonin transporter (SERT), plays a crucial role in aggression regulation. Here, we investigated region-specific, dynamic changes in SERT expression following aggressive interactions and in mice subjected to early-life social adversity. We found that aggressive encounters (resident-intruder test) triggered a significant, rapid increase in SERT immunoreactivity within 90 min, accompanied by neuronal activation in aggression-related brain regions, including the medial prefrontal cortex (mPFC), lateral septum (LS), medial amygdala (MeA), ventromedial hypothalamus (VMHvl), lateral habenula (LH), and dorsal raphe (DR), but not in the paraventricular thalamus (PVT). Notably, this SERT upregulation occurred across the aggression circuitry but was accompanied by a significant increase in 5-HT levels only in the mPFC, a key region in top-down regulation of social and aggressive behavior. This SERT upregulation was not observed following exposure to a non-social challenge, suggesting that it may be more specifically associated with social contexts. Using super-resolution microscopy, we identified an increased density of SERT localization points within serotonergic mPFC axons after an aggressive encounter. Social isolation during adolescence, a model of early social neglect, impaired this rapid SERT response, particularly in the ventral and medial orbitofrontal regions, and altered the relationship between SERT levels and aggression-related behaviors. These findings demonstrate that SERT expression undergoes rapid, experience-dependent plasticity in response to social aggression, and that early-life adversity disrupts this adaptive mechanism, providing new insights into the serotonergic regulation of aggression and its potential relevance for stress-related social dysfunctions.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100722"},"PeriodicalIF":4.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724224","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}