Neurobiology of Stress最新文献

{"title":"The zona incerta regulates burying behavior and normalizes anxiety-like behavior in inescapable stressful male mice by object cue","authors":"Yueqin Liu ,&nbsp;Lianli Qiu ,&nbsp;Jiahui Qian ,&nbsp;Qiang Xu ,&nbsp;Rongfeng Qi ,&nbsp;Yifeng Luo ,&nbsp;Zhihong Cao ,&nbsp;Zhiqiang Zhang ,&nbsp;Wei Wu ,&nbsp;Longjiang Zhang ,&nbsp;Guangming Lu","doi":"10.1016/j.ynstr.2024.100704","DOIUrl":"10.1016/j.ynstr.2024.100704","url":null,"abstract":"<div><div>Inescapable stressful events often precipitate long-term alterations in emotion-related behaviors and poor sleep quality, with anxiety being a prevalent associated disorder. The defensive burying behavior of rodents is a response to imminent threats that becomes markedly pronounced in response to anxiety. However, the neural foundations of defensive burying behavior and etiology of anxiety remain largely unknown. In this study, we established a model employing object binding to elicit increased burying behavior in mice, thereby enhancing fear resolution and subsequently reducing anxious behaviors. Notably, the mice that associated shock with an object exhibited less object exploration and the zona incerta (ZI) neurons showed higher calcium activity during object exploration as compared to the Shock only mice. Although the calcium activity in ZI neurons of the Object mice was identical to the Shock only mice, the Object mice exhibited more burying behavior. Furthermore, the time spent in the center of the open-field test was directly proportional to the duration of burying behavior. Chemogenetic activation of ZI neurons extended the burying time and concomitantly ameliorated anxiety-like behavior. Importantly, chemogenetic enhancement of projection from ZI neurons to the ventral periaqueductal gray (vPAG), a brain region that plays a critical role in autonomic function, normalizes anxious behavior without influencing burying behavior. Collectively, these findings systematically reveal the functions and underlying mechanisms of the ZI-vPAG circuit in controlling behaviors akin to anxiety, offering significant insights into ZI's role in the pathophysiology of anxiety disorders.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"34 ","pages":"Article 100704"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143140572","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":"Shared genetic risk and causal associations between Post-traumatic stress disorder and migraine with antithrombotic agents and other medications","authors":"Charlotte K. Bainomugisa ,&nbsp;The International Headache Genetics Consortium (IHGC),&nbsp;Dagmar Bruenig ,&nbsp;Heidi G. Sutherland ,&nbsp;Lyn R. Griffiths ,&nbsp;Dale R. Nyholt ,&nbsp;Divya Mehta","doi":"10.1016/j.ynstr.2024.100703","DOIUrl":"10.1016/j.ynstr.2024.100703","url":null,"abstract":"<div><div>Post-traumatic stress disorder (PTSD) is a psychiatric disorder that frequently co-occurs with pain disorders including migraine. There are proposed biological, genetic and environmental factors associated with both PTSD and migraine suggesting shared etiology. Genome-Wide Association Studies (GWAS) have been used to identify genomic risk loci associated with various disorders and to investigate genetic overlap between traits. There is a significant genetic correlation between PTSD and migraine with no evidence of a causal relationship that could be attributed to pleiotropy. Cross-disorder genetic analyses were applied to investigate the genetic overlap and causal associations using GWAS summary statistics of PTSD (<em>n</em> = 214408), migraine (<em>n</em> = 873341) and 23 medication use traits (<em>n</em> = 78808–305913) including anti-depressants, anti-migraine preparations and beta-blocking agents.</div><div>Across the entire genome, anti-thrombotic agents had a significant and negative genetic correlation with PTSD (rG = −0.2, <em>P</em>_FDR = 0.032) and a positive genetic correlation with migraine (rG = 0.26, <em>P</em>_FDR = 2.23 x 10⁻⁸). PTSD showed significant genetic correlation with 11 other medication use traits including beta blocking agents (rG = −0.11, <em>P</em>_FDR = 0.034). Of the 2495 genomic regions tested, PTSD showed significant local genetic correlation with 12 medication use traits at 43 loci; while migraine showed significant genetic correlation with only anti-inflammatory agents and anti-rheumatic products at locus 12:57522282–57607142 (<em>DAB1</em>) (<em>P</em> &lt; 2 x 10⁻⁵). The genetic liability to PTSD had a causal effect on increased risk of using pain medication such as opioids (<em>β</em>_ivw = 0.59, <em>P</em> = 5.21 x 10⁻⁵) while the genetic liability to migraine had a causal effect on the increased risk of using anti-thrombotic agents (<em>β</em>_ivw = 0.59, <em>P</em> = 1.69 x 10⁻⁷). The genes in the genomic regions shared between PTSD and medication use traits were enriched in neural-related pathways such as neuron development, neurogenesis and protein kinase activity. These results provide further insight into the genetically controlled biological and environmental factors underlying the shared etiology between PTSD and migraine. The identified biomarkers can be used as a basis for investigation as potential drug targets for both disorders. These findings are significant for drug re-purposing and treatment of PTSD and migraine using monotherapy.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"34 ","pages":"Article 100703"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080385","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":"Social context modulates active avoidance: Contributions of the anterior cingulate cortex in male and female rats","authors":"Shannon Ruble,&nbsp;Karissa Payne,&nbsp;Cassandra Kramer,&nbsp;Lexe West,&nbsp;Halle Ness,&nbsp;Greg Erickson,&nbsp;Alyssa Scott,&nbsp;Maria M. Diehl","doi":"10.1016/j.ynstr.2024.100702","DOIUrl":"10.1016/j.ynstr.2024.100702","url":null,"abstract":"<div><div>Actively avoiding danger is necessary for survival. Most research on active avoidance has focused on the behavioral and neurobiological processes when individuals learn to avoid alone, within a solitary context. Therefore, little is known about how social context affects active avoidance. Using a modified version of the platform-mediated avoidance task in rats, we investigated whether the presence of a social partner attenuates conditioned freezing and enhances avoidance compared to avoidance in a solitary context. Rats spent a similar amount of time avoiding during either context; however, rats trained in the social context exhibited greater freezing as well as lower rates of darting and food seeking compared to rats trained in the solitary context. In addition, we observed higher levels of avoidance in females compared to males in the solitary context, but this sex difference was not present in rats trained in the social context. To gain greater mechanistic insight, we optogenetically inactivated glutamatergic projection neurons in the anterior cingulate cortex (ACC) following avoidance training in either context. After avoidance was learned in a social context, photoinactivation of ACC reduced expression of avoidance during a test when the social partner was absent, but not when the partner was present. Our findings suggest a novel contribution of the ACC in avoidance that is learned with a social partner, which has translational implications for understanding ACC dysfunction in those suffering from trauma-related disorders.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"34 ","pages":"Article 100702"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906685","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":"Corticosterone-induced postpartum depression induces depression-like behavior and impairs hippocampal neurogenesis in adolescent offspring via HPA axis and BDNF-mTOR pathway","authors":"Hongxiao Xie ,&nbsp;Yanning Jiang ,&nbsp;Xiumeng Zhang ,&nbsp;Xinran Min ,&nbsp;Jiuseng Zeng ,&nbsp;Li Chen ,&nbsp;Nan Zeng ,&nbsp;Rong Liu","doi":"10.1016/j.ynstr.2025.100708","DOIUrl":"10.1016/j.ynstr.2025.100708","url":null,"abstract":"<div><div>Postpartum depression (PPD) adversely affects the growth and development of the offspring, increasing the risk of various internalizing behaviorsduring adolescence. Studies have shown that corticosterone (CORT)-induced PPD affects neurogenesis in the offspring, which is closely related to the onset of depression. However, the underlying mechanisms of these changes in the offspring of PPD mothers remain unexplored. In this study, we demonstrated postpartum mice treated with high CORT experienced activation of the hypothalamic-pituitary-adrenal (HPA) axis, which induced depressive-like behavior and impaired maternal caring behavior. Furthermore, adolescent offspring of PPD mice exhibited depression-like behavior, and learning and memory deficits. These offspring also showed diminished levels of DCX⁺, decreased levels of synaptic proteins, and reduced dendritic spine density and length in hippocampus. Additionally, we detected increased serum stressed hormones and decreased hippocampal glucocorticoid receptor (GR) protein level in the offspring. We also found the offspring exhibited reduced expression of brain-derived neurotrophic factor (BDNF) and the phosphorylation tyrosine kinase receptor B (TrkB), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) proteins in hippocampus. These results indicated that the behavioral deficits and neuronal damage observed in the offspring of PPD mice may be related to HPA axis dysfunction and inhibition of the BDNF-mTOR pathway. In conclusion, our findings confirm that CORT induces depression-like behavior and impairs maternal caring behavior in maternal mice, which in turn affects their offspring's emotion and cognitive behavior. This impact is characterized by the activation of the HPA axis and inhibition of the BDNF-mTOR pathway.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"34 ","pages":"Article 100708"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059616","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":"Mothering matters: Towards a better understanding of disrupted infant-caregiver relationships in both mother and offspring","authors":"Millie Rincón-Cortés","doi":"10.1016/j.ynstr.2024.100701","DOIUrl":"10.1016/j.ynstr.2024.100701","url":null,"abstract":"<div><div>The mother-infant bond is among the strongest social relationships formed in humans and nonhuman mammals. As such, disrupted infant-caregiver relationships have the capacity to result in potent adverse effects not only in the offspring, but also in the mother. Here, I provide a brief overview of my prior work showing adversity-induced alterations in offspring and maternal behavioral and brain function. I also share my vision for future directions for developmental and maternal neurobiology research in the context of stress and/or adversity exposure.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"34 ","pages":"Article 100701"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971689","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":"Stress reactivity moderates the association between early experiences of unpredictability and emotional problems in adolescents","authors":"J.L. Buthmann ,&nbsp;C. Antonacci ,&nbsp;J.P. Uy ,&nbsp;L.R. Borchers ,&nbsp;J.G. Miller ,&nbsp;I.H. Gotlib","doi":"10.1016/j.ynstr.2024.100706","DOIUrl":"10.1016/j.ynstr.2024.100706","url":null,"abstract":"<div><div>Researchers have documented that exposure to different kinds of psychosocial stressors can lead to emotional difficulties and, further, that heightened reactivity to stress can moderate these associations. Recently, investigators have distinguished among threat, deprivation, and unpredictability as different dimensions of early life stress (ELS). It is not clear, however, whether reactivity in specific stress response systems functions as a diathesis to lead to emotional difficulties following exposure to these dimensions of ELS. In this study (N = 154) we examined whether stress reactivity, assessed across different psychobiological systems during the Trier Social Stress Test, is a unitary or multidimensional construct, and if reactivity differentially moderates the associations between ELS dimensions and adolescents’ susceptibility to emotional and behavioral problems two years later. A factor analysis conducted on stress reactivity measures yielded two factors: one composed of reactivity in heart rate, heart rate variability, and cortisol, and one composed of reactivity in skin conductance and self-reported mood. These two factors independently moderated the associations between early unpredictability and subsequent emotional problems. For each factor, the combination of higher unpredictability and higher stress reactivity predicted higher emotional problems; stress reactivity factors were not significant moderators of the effects of threat and deprivation. Our findings suggest that increased stress reactivity, assessed across several domains of functioning, functions as a diathesis that interacts with ELS characterized by unpredictability to predict subsequent mental health difficulties in adolescents and, further, that low stress reactivity buffers against mental health difficulties in adolescents who have experienced unpredictability early in life.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"34 ","pages":"Article 100706"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984240","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":"Retrotransposons and the brain: Exploring a complex relationship between mobile elements, stress, and neurological health","authors":"Amelia Cuarenta","doi":"10.1016/j.ynstr.2025.100709","DOIUrl":"10.1016/j.ynstr.2025.100709","url":null,"abstract":"<div><div>Environmental experiences during early life, including stress, can significantly impact brain development and behavior. Early life stress (ELS) is linked to an increased risk for various psychiatric disorders including anxiety, depression, and substance use disorders. Epigenetic mechanisms have increasingly been of interest to understand how environmental factors contribute to reprogramming the brain and alter risk and resilience to developing psychiatric disorders. However, we know very little about mobile elements or the regulation of mobile elements and their contribution to psychiatric disorders. Recently, advances in genomics have contributed to our understanding of mobile elements, including the retrotransposon LINE-1 (L1) and their potential role in mediating environmental experiences. Yet we still do not understand how these elements may contribute to psychiatric disorders. Future research leveraging cutting-edge technologies will deepen our understanding of these mobile elements. By elucidating their role in development and how stress may impact them, we may unlock new avenues for therapeutic and diagnostic innovations.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"34 ","pages":"Article 100709"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143140734","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":"Integrative approaches to studying sleep, stress, and related disorders","authors":"Thomas C. Neylan,&nbsp;Gina R. Poe,&nbsp;Victoria B. Risbrough","doi":"10.1016/j.ynstr.2024.100700","DOIUrl":"10.1016/j.ynstr.2024.100700","url":null,"abstract":"","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"34 ","pages":"Article 100700"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143128169","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":"Brain receptor dynamics in early and adult life stress: Gateways to maladaptive coping strategies","authors":"Sora Shin","doi":"10.1016/j.ynstr.2025.100707","DOIUrl":"10.1016/j.ynstr.2025.100707","url":null,"abstract":"<div><div>Stress plays a significant role in the onset of numerous psychiatric disorders. Depending on individual resilience or stressor's nature, long-term changes to stress in the brain can lead to a wide range of behavioral symptoms, including social withdrawal, feelings of helplessness, and emotional overeating. The brain receptor molecules are key mediators of these processes, translating neuromodulatory signals into neuronal responses or circuit activity changes that ultimately shape behavioral outcomes. Here, I highlight several of my previous studies that reveal the pivotal role of receptor molecules in critical brain regions such as the nucleus accumbens, lateral hypothalamus, and lateral septum. I identified how mGluR5 signaling in the nucleus accumbens promotes stress resilience through pathways involving ΔFosB and SRF, while leptin receptor or glucocorticoid receptor signaling within lateral hypothalamic circuits contributes to stress eating. Additionally, I uncovered the role of dopamine receptor 3 signaling in the lateral septum in mediating the impact of early life stress on social behaviors. These findings underscore the functional relevance of brain receptor molecules in transducing stress—from early life through adulthood—into maladaptive coping behaviors. As druggable targets, these receptor-mediated pathways provide a critical foundation for developing targeted interventions to alleviate stress-related psychiatric symptoms.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"34 ","pages":"Article 100707"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059514","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":"Neuroanatomical prediction of individual anxiety problems level using machine learning models: A population-based cohort study of young adults","authors":"Hui Xu ,&nbsp;Jing Xu ,&nbsp;Dandong Li","doi":"10.1016/j.ynstr.2024.100705","DOIUrl":"10.1016/j.ynstr.2024.100705","url":null,"abstract":"<div><div>Anxiety, a mental state in healthy individuals, is characterized by apprehension of potential future threats. Though the neurobiological basis of anxiety has been investigated widely in the clinical populations, the underly mechanism of neuroanatomical correlates with anxiety level in healthy young adults is still unclear. In this study, 1080 young adults were enrolled from the Human Connectome Project Young Adult dataset, and machine learning-based elastic net regression models with cross validation, together with linear mix effects (LME) models were adopted to investigate whether the neuroanatomical profiles of structural magnetic resonance imaging indicators associated with anxiety level in healthy young adults. We found multi-region neuroanatomical profiles predicted anxiety problems level and it was still robust in an out-of-sample. The neuroanatomical profiles had widespread brain nodes, including the dorsal lateral prefrontal cortex, supramarginal gyrus, and entorhinal cortex, which implicated in the default mode network and frontoparietal network. This finding was further supported by LME models, which showed significant univariate associations between brain nodes with anxiety. In sum, it's a large sample size study with multivariate analysis methodology to provide evidence that individual anxiety problems level can be predicted by machine learning-based models in healthy young adults. The neuroanatomical signature including hub nodes involved theoretically relevant brain networks robustly predicts anxiety, which could aid the assessment of potential high-risk of anxiety individuals.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"34 ","pages":"Article 100705"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008817","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}