Neurobiology of Stress最新文献

{"title":"Acute stress activates basolateral amygdala neurons expressing corticotropin-releasing hormone receptor type 1 (CRHR1): Topographical distribution and projection-specific activation in male and female rats","authors":"Robert J. Aukema ,&nbsp;Gavin N. Petrie ,&nbsp;Samantha L. Baglot ,&nbsp;Nicholas W. Gilpin ,&nbsp;Matthew N. Hill","doi":"10.1016/j.ynstr.2024.100694","DOIUrl":"10.1016/j.ynstr.2024.100694","url":null,"abstract":"<div><div>Although the basolateral amygdala (BLA) and corticotropin releasing hormone receptor type I (CRHR1) signaling are both central to the stress response, the spatial and circuit-specific distribution of CRHR1 have not been identified in the BLA at a high resolution. We used transgenic male and female CRHR1-Cre-tdTomato rats to topographically map the distribution of BLA^CRHR1 neurons and identify whether they are activated by acute stress. Additionally, we used the BLA circuits projecting to the central amygdala (CeA) and nucleus accumbens (NAc) as a model to test circuit-specific expression of CRHR1 in the BLA. We established several key findings. First, CRHR1 had the strongest expression in the lateral amygdala and in caudal portions of the BLA. Second, acute restraint stress increased FOS expression of CRHR1 neurons, and stress-induced activation was particularly strong in medial subregions of the BLA. Third, stress significantly increased FOS expression on BLA-NAc, but not BLA-CeA projectors, and BLA-NAc activation was more robust in males than females. Finally, CRHR1 was expressed on a subset of BLA-CeA and BLA-NAc projection neurons. Collectively, this expands our understanding of BLA molecular- and circuit-specific activation patterns following acute stress.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100694"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660357","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":"Sex specific gut-microbiota signatures of resilient and comorbid gut-brain phenotypes induced by early life stress","authors":"Lars Wilmes ,&nbsp;Valentina Caputi ,&nbsp;Thomaz F.S. Bastiaanssen ,&nbsp;James M. Collins ,&nbsp;Fiona Crispie ,&nbsp;Paul D. Cotter ,&nbsp;Timothy G. Dinan ,&nbsp;John F. Cryan ,&nbsp;Gerard Clarke ,&nbsp;Siobhain M. O'Mahony","doi":"10.1016/j.ynstr.2024.100686","DOIUrl":"10.1016/j.ynstr.2024.100686","url":null,"abstract":"<div><h3>Background</h3><div>Alterations in gut-brain axis communication pathways and the gut microbiota ecosystem caused by early life stress have been extensively described as critical players in the pathophysiology of stress-induced disorders. However, the extent to which stress-induced gut microbiota alterations manifest in early life and contribute to the sex-specific susceptibility to distinct gut-brain phenotypes in adulthood has yet to be defined.</div></div><div><h3>Methods</h3><div>Male and female Sprague-Dawley rat offspring underwent maternal separation (3h/day from postnatal day 2–12). Faecal samples were collected before weaning for gut microbiota 16S rRNA sequencing and metabolomic analysis. Visceral pain sensitivity and negative valence behaviours were assessed in adulthood using colorectal distension and the forced swim test respectively. Behavioural data were processed in a two-step cluster analysis to identify groupings within the dataset. Multi-omics analysis was carried out to investigate if the microbial signatures following early life stress were already defined according to the membership of the adult behavioural phenotypes.</div></div><div><h3>Results</h3><div>Maternal separation resulted in increased visceral hypersensitivity while showing a trend for a sex-dependent increase in negative valence behaviour in adulthood. The cluster analysis revealed four clusters within the dataset representing distinct pathophysiological domains reminiscent of the behavioural consequences of early-life stress: 1. resilient, 2. pain, 3. immobile and 4. comorbid. The early life gut microbiota of each of these clusters show distinct alterations in terms of diversity, genus level differential abundance, and functional modules. Multi-omic integrations points towards a role for different metabolic pathways underlying each cluster-specific phenotype.</div></div><div><h3>Conclusion</h3><div>Our study is the first to identify distinct phenotypes defined by susceptibility or resilience to gut-brain dysfunction induced by early life stress. The gut microbiota in early life shows sex-dependent alterations in each cluster that precede specific behavioural phenotypes in adulthood. Future research is warranted to determine the causal relationship between early-life stress-induced changes in the gut microbiota and to understand the trajectory leading to the manifestation of different behavioural phenotypes in adulthood.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100686"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660354","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":"Basal cortisol level modulates stress-induced opioid-seeking behavior","authors":"Mark K. Greenwald ,&nbsp;Eric A. Woodcock ,&nbsp;Tabitha E.H. Moses ,&nbsp;Leslie H. Lundahl","doi":"10.1016/j.ynstr.2024.100684","DOIUrl":"10.1016/j.ynstr.2024.100684","url":null,"abstract":"<div><div>In preclinical studies and our human laboratory, the α₂-noradrenergic autoreceptor antagonist yohimbine was found to promote drug-seeking behavior. This study evaluated effects of dose-combinations of yohimbine and the glucocorticoid receptor agonist hydrocortisone to model intensity-dependent effects of stimulating each neurochemical system, alone and together, on stress-reactivity and opioid-seeking. Twelve regular heroin-using participants diagnosed with opioid use disorder (OUD) were stabilized on sublingual buprenorphine (8-mg/day), then passed a hydromorphone 18-mg vs. placebo intramuscular reinforcement screen. Across 9 experimental conditions (3 × 3 within-subject, randomized crossover, placebo-controlled, double-blind design) during inpatient buprenorphine maintenance, combinations of oral pretreatment doses of yohimbine (0, 27, 54-mg; <em>t</em> = 0 min) then hydrocortisone (0, 20, 40-mg; <em>t</em> = 45 min) were administered. In each condition, subjective drug and mood effects, cardiovascular responses, and saliva cortisol and α-amylase levels were assessed to evaluate stress-reactivity, and participants completed a 12-trial choice progressive ratio task during which they could earn units of hydromorphone (1.5-mg intramuscular) and/or money ($2.00). Yohimbine dose-dependently increased blood pressure, α-amylase, and anxiety scores, and decreased opioid agonist symptoms; hydrocortisone dose-dependently increased cortisol levels. Yohimbine/hydrocortisone dose-combinations significantly shifted within-session responding from money to opioid-seeking among participants with lower basal cortisol levels. These findings replicate yohimbine effects on stress biomarkers and demonstrate that noradrenergic/glucocorticoid-potentiated opioid-seeking is modulated by basal cortisol level. In persons with OUD stabilized on buprenorphine, basal HPA-axis activity and acute stressors can enhance opioid relative reinforcing efficacy. These factors may limit OUD treatment efficacy and highlight the need for novel interventions that prevent stress-induced opioid-seeking.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100684"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142539689","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":"Opposing effects of pre-encoding stress on neural substrates of item and emotional contextual source memory retrieval","authors":"Carlos Ventura-Bort ,&nbsp;Janine Wirkner ,&nbsp;Julia Wendt ,&nbsp;Lars Schwabe ,&nbsp;Florin Dolcos ,&nbsp;Alfons O. Hamm ,&nbsp;Mathias Weymar","doi":"10.1016/j.ynstr.2024.100691","DOIUrl":"10.1016/j.ynstr.2024.100691","url":null,"abstract":"<div><div>Although the mediating role of the stress hormone systems in memory for single— especially emotional— events is well-stablished, less is known about the influence of stress on memory for associated contextual information (source memory). Here, we investigated the impact of acute stress on the neural underpinnings of emotional contextual source memory. Participants underwent a stress or a control manipulation before they encoded objects paired with pleasant, neutral, or unpleasant backgrounds. One week later, item and contextual source memory were tested. Acute stress modulated the neural signature of item and contextual source memory in an opposite fashion: stressed participants showed larger activation in the precuneus and the medial prefrontal cortex (mPFC) during the retrieval of items, while the retrieval of contextual unpleasant information was associated with lower activation in the angular gyrus (AG) and mPFC. Furthermore, as revealed by cross-region representational similarity analyses, stress also reduced the memory reinstatement of the previously encoded visual cortex representations of object/unpleasant background pairings in the AG and mPFC. These results suggest that pre-encoding stress induction increases the activity of memory-related regions for single items but reduces the activity of these regions during the retrieval of contextual unpleasant information. Our findings provide new insights into the dissociative effects of stress on item and contextual source memory which could have clinical relevance for stress-related disorders.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100691"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660358","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":"Transient impact of chronic social stress on effort-based reward motivation in non-food restricted mice: Involvement of corticosterone","authors":"Danina Evertse ,&nbsp;Pilar Alves-Martinez ,&nbsp;Giulia Treccani ,&nbsp;Marianne B. Müller ,&nbsp;Frank J. Meye ,&nbsp;Michael A. van der Kooij","doi":"10.1016/j.ynstr.2024.100690","DOIUrl":"10.1016/j.ynstr.2024.100690","url":null,"abstract":"<div><div>Chronic stress has been connected to a reduced effort and motivational deficits. To study effort-based motivation in rodents, operant conditioning is often employed. However, caloric restriction is typically imposed simultaneously. Since caloric restriction is a stressor in its own right, this procedure interferes with data interpretation. Here, we investigate whether chronic social defeat stress (CSD), lasting 10 consecutive days, would alter effort-based reward motivation in mice trained under <em>ad libitum</em> food conditions. Utilizing operant FED3 boxes in home cages, mice were trained within eight days to nose poke for palatable food. After training completion, operant memory was retained for at least 16 days, and mice demonstrated sustained effort, as assessed with a progressive ratio schedule, to obtain reward pellets. Directly after CSD exposure (10th day), mice exhibited reduced effort for palatable food rewards, but also displayed reduced nose poking in general. The effects of CSD on effort were short-lived, with no lasting impact on effort-based reward motivation one week post-stress. As corticosterone (CORT) levels were increased at day 10 of CSD, but not at day 17, we hypothesized that CORT might mediate the acute effects of CSD on effort-based reward motivation. Indeed, CORT administration [100 μg/ml], supplied via the drinking water, mirrored the CSD-induced CORT spike and temporarily reduced reward motivation. Our findings emphasize that CSD does not result in long-term deficits in reward motivation, suggesting a resilient adaptive response in mice under unrestricted feeding conditions. This study underscores the necessity of considering temporal dynamics of stress impacts and highlights the modulating effects of CORT. These insights contribute to a deeper understanding of the resilience mechanisms in motivational impairments and pave the way for further research into factors facilitating this resilience.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100690"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660356","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":"Prenatal exposures and cell type proportions are main drivers of FKBP5 DNA methylation in maltreated and non-maltreated children","authors":"Vera N. Karlbauer ,&nbsp;Jade Martins ,&nbsp;Monika Rex-Haffner ,&nbsp;Susann Sauer ,&nbsp;Simone Roeh ,&nbsp;Katja Dittrich ,&nbsp;Peggy Doerr ,&nbsp;Heiko Klawitter ,&nbsp;Sonja Entringer ,&nbsp;Claudia Buss ,&nbsp;Sibylle M. Winter ,&nbsp;Christine Heim ,&nbsp;Darina Czamara ,&nbsp;Elisabeth B. Binder","doi":"10.1016/j.ynstr.2024.100687","DOIUrl":"10.1016/j.ynstr.2024.100687","url":null,"abstract":"<div><div>DNA methylation in peripheral tissues may be a relevant biomarker of risk for developing mental disorders after exposure to early life adversity. Genes involved in HPA axis regulation, such as <em>FKBP5</em>, might play a key role. In this study, we aimed to identify the main drivers of salivary <em>FKBP5</em> methylation in a cohort of 162 maltreated and non-maltreated children aged 3–5 years at two measurement timepoints. We combined data from a targeted bisulfite sequencing approach for fine-mapping 49 CpGs in regulatory regions of <em>FKBP5</em> and epigenetic scores for exposure to alcohol, cigarette smoke, and glucocorticoids derived from the EPICv1 microarray.</div><div>Most variability of methylation in the <em>FKBP5</em> locus was explained by estimated cell type proportions as well as epigenetic exposure scores, most prominently by the glucocorticoid exposure score. While not surviving correction for multiple testing, we replicated previously reported associations of <em>FKBP5</em> methylation with CM. We also detected synergistic effects of both rs1360780 genotype and the glucocorticoid exposure score on <em>FKBP5</em> hypomethylation. These effects were identified in the 3′TAD, a distal regulatory region of <em>FKBP5</em> which is not extensively covered in Illumina arrays, emphasizing the need for fine mapping approaches. Additionally, the epigenetic glucocorticoid exposure score was associated with childhood maltreatment, maternal mental disorders, and pregnancy complications, thereby highlighting the role of glucocorticoid signaling in the epigenetic consequences of early adversity.</div><div>These results underscore the need to assess cell type heterogeneity in targeted assessments of DNA methylation and show the impact of exposures beyond just childhood maltreatment such as glucocorticoid exposure.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100687"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706091","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 media prefrontal cortex astrocytic activity in response to negative stimuli in male mice","authors":"Ai-Mei Wu ,&nbsp;Jing-Ya Zhang ,&nbsp;Wei-Zhong Lun ,&nbsp;Zhi Geng ,&nbsp;Ye Yang ,&nbsp;Jun-Cang Wu ,&nbsp;Gui-Hai Chen","doi":"10.1016/j.ynstr.2024.100676","DOIUrl":"10.1016/j.ynstr.2024.100676","url":null,"abstract":"<div><div>Astrocytes play significant roles in regulating the central stress response. Chronic stress impairs the structure and function of astrocytes in many brain regions such as media prefrontal cortex (mPFC) in multiple neuropsychiatric conditions, but the astrocytic dynamics on the timescale of behavior remains unclear. Here, we recorded mPFC astrocytic activity in freely behaving mice and found that astrocytes are activated immediately by different aversive stimuli. Astrocyte specific GCaMP6s calcium indicator were virally expressed in mPFC astrocytes and fiber photometry experiments revealed that astrocytes are activated by tail-restraint (TRT), foot shock (FS), open arm exploration, stressor of height, predator odor and social defeat (SD) stress. ΔF/F analyses demonstrated that an unpredictable stimulus such as elevated platform stress (EPS) at the initial encounter induced the most intense and rapid changes in astrocytic calcium activity, while a predictable 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) stimulus resulted in the weakest response with a longer peak latency. In TRT, FS or SD test, a somatic stimulus led to higher average calcium activity level and faster average peak latency in repeated trails. Similar to TMT stimulus, astrocytic calcium activity in elevated plus maze (EPM) test exhibited a smaller average change in amplitude and the longest peak latency during open arm exploration. Moreover, astrocytic calcium activity exhibited different changes across behavioral states in SD tests. Our findings show that mPFC astrocytes exhibit distinct patterns of calcium activity in response to various negative stimuli, indicating that the dynamic activity of astrocytes may reflect the stress-related behavioral state under different stimulus conditions.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100676"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142420393","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":"Effects of chronic stress on cognitive function – From neurobiology to intervention","authors":"Milena Girotti ,&nbsp;Sarah E. Bulin,&nbsp;Flavia R. Carreno","doi":"10.1016/j.ynstr.2024.100670","DOIUrl":"10.1016/j.ynstr.2024.100670","url":null,"abstract":"<div><p>Exposure to chronic stress contributes considerably to the development of cognitive impairments in psychiatric disorders such as depression, generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and addictive behavior. Unfortunately, unlike mood-related symptoms, cognitive impairments are not effectively treated by available therapies, a situation in part resulting from a still incomplete knowledge of the neurobiological substrates that underly cognitive domains and the difficulty in generating interventions that are both efficacious and safe.</p><p>In this review, we will present an overview of the cognitive domains affected by stress with a specific focus on cognitive flexibility, behavioral inhibition, and working memory. We will then consider the effects of stress on neuronal correlates of cognitive function and the factors which may modulate the interaction of stress and cognition. Finally, we will discuss intervention strategies for treatment of stress-related disorders and gaps in knowledge with emerging new treatments under development.</p><p>Understanding how cognitive impairment occurs during exposure to chronic stress is crucial to make progress towards the development of new and effective therapeutic approaches.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100670"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000663/pdfft?md5=74817e2bd3e26a3097145e164803e3b3&pid=1-s2.0-S2352289524000663-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157401","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":"Interaction between corticotropin-releasing factor, orexin, and dynorphin in the infralimbic cortex may mediate exacerbated alcohol-seeking behavior","authors":"Francisco J. Flores-Ramirez ,&nbsp;Jessica M. Illenberger ,&nbsp;Rémi Martin-Fardon","doi":"10.1016/j.ynstr.2024.100695","DOIUrl":"10.1016/j.ynstr.2024.100695","url":null,"abstract":"<div><div>A major challenge for the treatment of alcohol use disorder (AUD) is relapse to alcohol use, even after protracted periods of self-imposed abstinence. Stress significantly contributes to the chronic relapsing nature of AUD, given its long-lasting ability to elicit intense craving and precipitate relapse. As individuals transition to alcohol dependence, compensatory allostatic mechanisms result in insults to hypothalamic-pituitary-adrenal axis function, mediated by corticotropin-releasing factor (CRF), which is subsequently hypothesized to alter brain reward pathways, influence affect, elicit craving, and ultimately perpetuate problematic drinking and relapse vulnerability. Orexin (OX; also called hypocretin) plays a well-established role in regulating diverse physiological processes, including stress, and has been shown to interact with CRF. Interestingly, most hypothalamic cells that express <em>Ox</em> mRNA also express <em>Pdyn</em> mRNA. Both dynorphin and OX are located in the same synaptic vesicles, and they are co-released. The infralimbic cortex (IL) of the medial prefrontal cortex (mPFC) has emerged as being directly involved in the compulsive nature of alcohol consumption during dependence. The IL is a CRF-rich region that receives OX projections from the hypothalamus and where OX receptor mRNA has been detected. Although not thoroughly understood, anatomical and behavioral pharmacology data suggest that CRF, OX, and dynorphin may interact, particularly in the IL, and that functional interactions between these three systems in the IL may be critical for the etiology and pervasiveness of compulsive alcohol seeking in dependent subjects that may render them vulnerable to relapse. The present review presents evidence of the role of the IL in AUD and discusses functional interactions between CRF, OX, and dynorphin in this structure and how they are related to exacerbated alcohol drinking and seeking.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100695"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706093","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":"Enduring memory consequences of early-life stress / adversity: Structural, synaptic, molecular and epigenetic mechanisms","authors":"Tallie Z. Baram ,&nbsp;Matthew T. Birnie","doi":"10.1016/j.ynstr.2024.100669","DOIUrl":"10.1016/j.ynstr.2024.100669","url":null,"abstract":"<div><p>Adverse early life experiences are strongly associated with reduced cognitive function throughout life. The link is strong in many human studies, but these do not enable assigning causality, and the limited access to the live human brain can impede establishing the mechanisms by which early-life adversity (ELA) may induce cognitive problems. In experimental models, artificially imposed chronic ELA/stress results in deficits in hippocampus dependent memory as well as increased vulnerability to the deleterious effects of adult stress on memory. This causal relation of ELA and life-long memory impairments provides a framework to probe the mechanisms by which ELA may lead to human cognitive problems. Here we focus on the consequences of a one-week exposure to adversity during early postnatal life in the rodent, the spectrum of the ensuing memory deficits, and the mechanisms responsible. We highlight molecular, cellular and circuit mechanisms using convergent trans-disciplinary approaches aiming to enable translation of the discoveries in experimental models to the clinic.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100669"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000651/pdfft?md5=0dae508822ab66e17bb389e4c4ca6c65&pid=1-s2.0-S2352289524000651-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164492","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}