Neurobiology of Stress最新文献

{"title":"The link between early-life adversity and later alcohol use disorder: A role for microglia?","authors":"Hannah D. Lichtenstein,&nbsp;Michelle K. Sequeira,&nbsp;Jessica L. Bolton","doi":"10.1016/j.ynstr.2025.100714","DOIUrl":"10.1016/j.ynstr.2025.100714","url":null,"abstract":"<div><div>In the clinical literature, early-life adversity (ELA) has been highly associated with the later development of alcohol misuse and alcohol use disorder (AUD). Adolescence is a period of vulnerability for the development of neuropsychiatric disorders like depression and substance use disorders like AUD, both of which have been shown to have increased risk due to ELA. Experimentation with alcohol use in adolescence is quite common, but some adolescents that engage in alcohol experimentation become prone to alcohol misuse. Here, we review evidence that experiencing ELA prior to adolescent alcohol use could make individuals more susceptible to developing AUD, and consider the neural mechanisms that may underlie this vulnerability. We focus on the potential role of microglia, the resident immune cells of the brain, which are important for sculpting brain circuits during development and are highly sensitive to environmental perturbations. We discuss the microglia-mediated developmental processes within the stress- and reward-related regions of the brain, particularly those with corticotropin-releasing factor (CRF)-expressing neurons, and how these regions can be impacted by both ELA and alcohol use. Finally, we point to the gaps in the literature surrounding the link between ELA and AUD, and how investigating microglia in the context of this “2-hit model” may shed light on possible interventions and therapeutics that can be developed for this specific clinical population.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"35 ","pages":"Article 100714"},"PeriodicalIF":4.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561933","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 impact of distal stress on the spontaneous recovery of conditioned defensive responses","authors":"Christopher M. Klinke ,&nbsp;Maren D. Lange ,&nbsp;Marta Andreatta","doi":"10.1016/j.ynstr.2025.100715","DOIUrl":"10.1016/j.ynstr.2025.100715","url":null,"abstract":"<div><div>Intense and chronic stress strengthens fear memories and increases the risk for mental disorders. Often stressful situations are experienced long before the appearance of the symptoms, but so far, little has been investigated on how distal stress alters fear memories. In a four-day paradigm, 131 healthy individuals were either assigned to the stress-group by means of the socially evaluated cold-pressor test (SECPT) or to the sham-group (control condition). Twenty-four hours later, participants underwent fear acquisition during which two shapes were presented. The first shape (conditioned stimulus, CS+) was associated with an electro-tactile stimulation (unconditioned stimulus, US), whereas the second shape (CS-) were presented alone. During extinction training, both shapes were presented while the US was omitted. To investigate if stress induction alters extinction recall differently depending on the passage of time, participants were tested either one day (recent) or 15 days (remote) after extinction training. Learning was quantified via subjective ratings, startle reflex and skin conductance response. While we found successful acquisition and extinction of the conditioned defensive responses, there was no effect of stress on these learning processes. Stress induction did not alter the spontaneous recovery of the conditioned defensive verbal responses but of the physiological responses as stressed individuals tested two weeks after extinction training showed startle potentiation to CS + vs. CS-. In conclusion, distal stress, even if mild, can strengthen fear memories and weaken extinction memory by the passage of time. This could be a possible mechanism facilitating the onset of stress-related and anxiety disorders.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"35 ","pages":"Article 100715"},"PeriodicalIF":4.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600861","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":"Early-life stress sensitizes response to future stress: Evidence and mechanisms","authors":"Catherine Jensen Peña","doi":"10.1016/j.ynstr.2025.100716","DOIUrl":"10.1016/j.ynstr.2025.100716","url":null,"abstract":"<div><div>Early-life stress sensitizes individuals to additional stressors and increases lifetime risk for mood and anxiety disorders. Research in both human populations and rodent models of early-life stress have sought to determine how different types of stressors contribute to vulnerability, and whether there are developmental sensitive periods for such effects. Although differences in the type and timing of rodent early-life stress paradigms have led to differences in specific behavioral outcomes, this complexity is present among humans as well. Robust rodent research now shows how early-life stress increases sensitivity to future stressors at behavioral, neural circuit, and molecular levels. These recent discoveries are laying the foundation for translation to more effective interventions relevant for those who experienced childhood stress and trauma.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"35 ","pages":"Article 100716"},"PeriodicalIF":4.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600862","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":"Gut Microbiome-Liver-Brain axis in Alcohol Use Disorder. The role of gut dysbiosis and stress in alcohol-related cognitive impairment progression: possible therapeutic approaches","authors":"Emilio Merlo Pich ,&nbsp;Ioannis Tarnanas ,&nbsp;Patrizia Brigidi ,&nbsp;Ginetta Collo","doi":"10.1016/j.ynstr.2025.100713","DOIUrl":"10.1016/j.ynstr.2025.100713","url":null,"abstract":"<div><div>The Gut Microbiome-Liver-Brain Axis is a relatively novel construct with promising potential to enhance our understanding of Alcohol Use Disorder (AUD), and its therapeutic approaches. Significant alterations in the gut microbiome occur in AUD even before any other systemic signs or symptoms manifest. Prolonged and inappropriate alcohol consumption, by affecting the gut microbiota and gut mucosa permeability, is thought to contribute to the development of behavioral and cognitive impairments, leading to Alcohol-Related Liver Disorders and potentially progressing into alcoholic cirrhosis, which is often associated with severe cognitive impairment related to neurodegeneration, such as hepatic encephalopathy and alcoholic dementia.</div><div>The critical role of the gut microbiota is further supported by the efficacy of FDA-approved treatments for hepatic encephalopathy in alcoholic cirrhosis (i.e., lactulose and rifaximin). To stimulate new research, we hypothesize that interactions between a maladaptive stress response and a constitutional predisposition to neurodegeneration underlie the progression of AUD to conditions of Alcohol-Related Clinical Concerns with severe cognitive impairment, which represent a significant and costly burden to society. Early identification of AUD individuals at risk for developing these conditions could help to prioritize integrated therapeutic interventions targeting different substrates of the Gut Microbiome-Liver-Brain axis. Specifically, addiction medications, microbiome modulators, stress-reducing interventions, and, possibly soon, novel agents that reduce hepatic steatosis/fibrosis will be discussed in the context of digitally supported integrated therapeutic approaches. The explicit goal of this AUD treatment performed on the early stage of the disorder would be to reduce the transition from AUD to those conditions of Alcohol-Related Common Clinical Concerns associated with severe cognitive impairment, a strategy recommended for most neurological neurodegenerative disorders.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"35 ","pages":"Article 100713"},"PeriodicalIF":4.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488250","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":"Illuminating the impact of stress: In vivo approaches to track stress-related neural adaptations","authors":"Puja K. Parekh","doi":"10.1016/j.ynstr.2025.100712","DOIUrl":"10.1016/j.ynstr.2025.100712","url":null,"abstract":"<div><div>Stressful experiences can affect both daily life and long-term health outcomes in a variety of ways. Acute challenges may be adaptive, promoting arousal and enhancing memory and cognitive function. Importantly, however, chronic stress dysregulates the body's physiological regulatory mechanisms consisting of complex hormone interactions throughout the peripheral and central nervous systems. This disrupted signaling consequently alters the balance of synapse formation, maturation and pruning, processes which regulate neural communication, plasticity, learning, cognitive flexibility and adaptive behaviors - hallmarks of a healthy, functional brain. The chronically stressed brain state, therefore, is one which may be uniquely vulnerable. To understand the development of this state, how it is sustained and how behavior and neural function are transiently or indelibly impacted by it, we can turn to a number of advanced approaches in animal models which offer unprecedented insights. This has been the aim of my recent work within the field and the goal of my new independent research program. To achieve this, I have employed methods to uncover how key brain circuits integrate information to support motivated behaviors, how stress impacts their ability to perform this process and how best to operationalize behavioral readouts. Here I present an overview of research contributions that I find most meaningful for advancing our understanding of the impact of stress and propose new avenues which will guide my own framework to address the salient outstanding questions within the field.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"35 ","pages":"Article 100712"},"PeriodicalIF":4.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394595","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 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":"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":"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":"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}