Neurobiology of Stress最新文献

{"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":"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":"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":"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":"Dopamine and D1 receptor in hippocampal dentate gyrus involved in chronic stress-induced alteration of spatial learning and memory in rats","authors":"Linping Wang ,&nbsp;Weiyao Wang ,&nbsp;Yingshun Li ,&nbsp;Hua Jin ,&nbsp;Bin Xiao ,&nbsp;Qinghua Jin","doi":"10.1016/j.ynstr.2024.100685","DOIUrl":"10.1016/j.ynstr.2024.100685","url":null,"abstract":"<div><div>There is increasing evidence that chronic stress (CS), which occurs when the body is exposed to prolonged stressors, significantly impairs learning and memory. Dopamine (DA) plays a critical role in learning and memory in the hippocampus through the activation of D1-like receptors (D1R). However, the specific roles of DA and D1R in the hippocampal dentate gyrus (DG), particularly in CS-induced changes in spatial learning and memory, are not well understood. In this study, we established a CS rat model through the random application of various stressors. We assessed spatial learning and memory using the Morris water maze (MWM) and measured DA concentration and the amplitude of field excitatory postsynaptic potentials (fEPSP) in the DG during the MWM test in freely moving rats. We also examined the involvement of D1R in spatial learning and memory by microinjecting its antagonist (SCH23390) into the DG, and then analyzed the expressions of phosphorylated (p-) Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), protein kinase A (PKA), and cAMP-response element binding protein (CREB) in the DG using Western blot. During the MWM test, compared with the control group, the escape latency was increased, and the percentage of distance in target quadrant and the number of platform crossings were decreased, in addition, the increase of fEPSP amplitude in the DG was significantly attenuated in CS group. In the control group, the DA concentration in the DG was significantly increased during the MWM test, and this response was enhanced in the CS group. Microinjection of SCH23390 into the DG significantly improved the spatial learning and memory impairments in CS rats, and reversed the inhibitory effect of CS on increase of fEPSP amplitude in the DG during the MWM test. Furthermore, SCH23390 partially reversed the inhibitory effects of CS on the expressions of p-CaMKII, p-PKA, and p-CREB in the DG. Our findings suggest that overactivation of the DA-D1R system in the hippocampal DG impairs spatial learning and memory and related synaptic plasticity in CS rats via downregulation of PKA-CREB signaling pathway.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100685"},"PeriodicalIF":4.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526526","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":"2024-10-24","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":"Stress resilience is an active and multifactorial process manifested by structural, functional, and molecular changes in synapses","authors":"E. Bączyńska ,&nbsp;M. Zaręba-Kozioł ,&nbsp;B. Ruszczycki ,&nbsp;A. Krzystyniak ,&nbsp;T. Wójtowicz ,&nbsp;K. Bijata ,&nbsp;B. Pochwat ,&nbsp;M. Magnowska ,&nbsp;M. Roszkowska ,&nbsp;I. Figiel ,&nbsp;J. Masternak ,&nbsp;A. Pytyś ,&nbsp;J. Dzwonek ,&nbsp;R. Worch ,&nbsp;K.H. Olszyński ,&nbsp;A.D. Wardak ,&nbsp;P. Szymczak ,&nbsp;J. Labus ,&nbsp;K. Radwańska ,&nbsp;P. Jahołkowski ,&nbsp;J. Włodarczyk","doi":"10.1016/j.ynstr.2024.100683","DOIUrl":"10.1016/j.ynstr.2024.100683","url":null,"abstract":"<div><div>Stress resilience is the ability of neuronal networks to maintain their function despite the stress exposure. Using a mouse model we investigate stress resilience phenomenon. To assess the resilient and anhedonic behavioral phenotypes developed after the induction of chronic unpredictable stress, we quantitatively characterized the structural and functional plasticity of excitatory synapses in the hippocampus using a combination of proteomic, electrophysiological, and imaging methods. Our results indicate that stress resilience is an active and multifactorial process manifested by structural, functional, and molecular changes in synapses. We reveal that chronic stress influences palmitoylation of synaptic proteins, whose profiles differ between resilient and anhedonic animals. The changes in palmitoylation are predominantly related with the glutamate receptor signaling thus affects synaptic transmission and associated structures of dendritic spines. We show that stress resilience is associated with structural compensatory plasticity of the postsynaptic parts of synapses in CA1 subregion of the hippocampus.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100683"},"PeriodicalIF":4.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526525","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-induced cortisol response predicts empathy for pain: The role of task-based connectivity between the insula and sensorimotor cortex during acute stress","authors":"Zihan Tang ,&nbsp;Yadong Liu ,&nbsp;Xiaolin Zhao ,&nbsp;Weiyu Hu ,&nbsp;Mengning Zhang ,&nbsp;Yipeng Ren ,&nbsp;Zhenni Wei ,&nbsp;Juan Yang","doi":"10.1016/j.ynstr.2024.100682","DOIUrl":"10.1016/j.ynstr.2024.100682","url":null,"abstract":"<div><div>Empathy for pain is a key driver of prosocial behavior and is influenced by acute psychosocial stress. However, the role of task-based brain connectivity during acute stress have been neglected. Hence, we aimed to explore the relationship between the magnitude of cortisol response to acute stress and empathy for pain, as well as the neural connectivity mechanisms involved. In this study, 80 healthy participants (37 women and 43 men) were exposed to the acute psychosocial stress paradigm (ScanSTRESS) and were scanned by functional magnetic resonance imaging. Saliva samples were collected to measure the magnitude of cortisol stress response. Subsequently, the participants took part in a pain-video task to assess their empathy for pain. Six participants were excluded because of physical discomfort or excessive head movement in all runs during the task-dependent fMRI scan. Therefore, 33 women and 41 men were included in data analysis. We found that empathy for pain was negatively correlated with the magnitude of cortisol stress response (<em>r</em> = -0.268, <em>p</em> = 0.018) and that the task-based connectivity between the salience network and sensorimotor network, including its sub-network and sub-region, was negatively correlated with the magnitude of cortisol stress response, and positively correlated with empathy for pain. Furthermore, task-based connectivity between the insula and the paracentral lobule mediates the effect of the stress-induced cortisol response on empathy for pain (indirect effect = -0.0152, 95% CI = [-0.036, -0.001], <em>p</em> = 0.036). Our research suggests that empathy is not only correlated with stress-induced glucocorticoids but also tied to the stress-induced reduced communication between basic and higher brain regions.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100682"},"PeriodicalIF":4.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526679","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":"Intra-BLA alteration of interneurons’ modulation of activity in rats, reveals a dissociation between effects on anxiety symptoms and extinction learning","authors":"Rinki Saha ,&nbsp;Lisa-Sophie Wüstner ,&nbsp;Darpan Chakraborty ,&nbsp;Rachel Anunu ,&nbsp;Silvia Mandel ,&nbsp;Joyeeta Dutta Hazra ,&nbsp;Martin Kriebel ,&nbsp;Hansjuergen Volkmer ,&nbsp;Hanoch Kaphzan ,&nbsp;Gal Richter-Levin","doi":"10.1016/j.ynstr.2024.100681","DOIUrl":"10.1016/j.ynstr.2024.100681","url":null,"abstract":"<div><div>The basolateral amygdala (BLA) is a dynamic brain region involved in emotional experiences and subject to long-term plasticity. The BLA also modulates activity, plasticity, and related behaviors associated with other brain regions, including the mPFC and hippocampus. Accordingly, intra-BLA plasticity can be expected to alter both BLA-dependent behaviors and behaviors mediated by other brain regions. Lasting intra-BLA plasticity may be considered a form of metaplasticity, since it will affect subsequent plasticity and response to challenges later on. Activity within the BLA is tightly modulated by GABAergic interneurons, and thus inducing lasting alteration of GABAergic modulation of principal neurons may have an impactful metaplastic effect on BLA functioning. Previously, we demonstrated that intra-BLA knockdown (KD) of neurofascin (NF) reduced GABAergic synapses exclusively at the axon initial segment (AIS). Here, by reducing the expression of the tyrosine kinase receptor ephrin A7 (EphA7), we selectively impaired the modulatory function of a different subpopulation of interneurons, specifically targeting the soma and proximal dendrites of principal neurons. This perturbation induced an expected reduction in the spontaneous inhibitory synaptic input and an increase in the excitatory spontaneous synaptic activity, most probably due to the reduction of inhibitory tone. Moreover, this increased synaptic activity was followed by a reduction in intrinsic excitability. While intra-BLA NF-KD resulted in impaired extinction learning, without increased symptoms of anxiety, intra-BLA reduction of EphA7 expression resulted in increased symptoms of anxiety, as measured in the elevated plus maze, but without affecting fear conditioning or extinction learning. These results confirm the role of the BLA and intra-BLA metaplasticity in stress-induced increased anxiety symptoms and in impaired fear extinction learning but reveals a difference in intra-BLA mechanisms involved. The results also confirm the contribution of GABAergic interneurons to these effects but indicate selective roles for different subpopulations of intra-BLA interneurons.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100681"},"PeriodicalIF":4.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526524","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":"Transcriptomic analysis of rat prefrontal cortex following chronic stress induced by social isolation – Relevance to psychiatric and neurodevelopmental illness, and implications for treatment","authors":"Jen-Yin Goh ,&nbsp;Patricia Rueda ,&nbsp;Joy Taylor ,&nbsp;Alex Rathbone ,&nbsp;Daniel Scott ,&nbsp;Christopher J. Langmead ,&nbsp;Kevin C.F. Fone ,&nbsp;Gregory D. Stewart ,&nbsp;Madeleine V. King","doi":"10.1016/j.ynstr.2024.100679","DOIUrl":"10.1016/j.ynstr.2024.100679","url":null,"abstract":"<div><div>Social isolation is an established risk factor for psychiatric illness, and became increasingly topical with the spread of SARS-CoV-2. We used RNA sequencing (RNA-Seq) to enable unbiased assessment of transcriptomic changes within the prefrontal cortex (PFC) of isolation-reared rats. To provide insight into the relevance of this manipulation for studying human illness, we compared differentially expressed genes (DEGs) and enriched biological functions against datasets involving post-mortem frontal cortical tissue from patients with psychiatric and neurodevelopmental illnesses. Sixteen male Sprague-Dawley rats were reared in groups of four or individually from weaning on postnatal day (PND) 22–24 until PFC tissue collection for RNA-Seq (PND64-66). We identified a total of 183 DEGs in isolates, of which 128 mirrored those in PFC tissue from patients with stress-related mental illnesses and/or neurodevelopmental conditions featuring social deficits. Seventy-one encode proteins classed as druggable by the gene-drug interaction database. Interestingly there are antagonists or inhibitors for the products of three of these up-regulated DEGs (<em>Hrh3</em>, <em>Snca</em> and <em>Sod1</em>) and agonists or activators for products of six of these down-regulated DEGs (<em>Chrm4</em>, <em>Klf2</em>, <em>Lrrk2</em>, <em>Nr4a1</em>, <em>Nr4a3</em> and <em>Prkca</em>). Some have already undergone pre-clinical and clinical evaluation, and studies with the remainder may be warranted. Changes to <em>Hrh3</em>, <em>Sod1</em>, <em>Chrm4</em>, <em>Lrrk2</em>, <em>Nr4a1</em> and <em>Prkca</em> were replicated in an independent cohort of sixteen male Sprague-Dawley rats via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Our findings support the continued use of post-weaning isolation rearing to investigate the neurobiology of stress-related disorders and evaluate therapeutic targets.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100679"},"PeriodicalIF":4.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526671","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}