Pub Date : 2024-11-01Epub Date: 2024-09-21DOI: 10.1016/j.ynstr.2024.100675
Julia R. Mitchell , Lindsay Vincelette , Samantha Tuberman , Vivika Sheppard , Emmett Bergeron , Roberto Calitri , Rose Clark , Caitlyn Cody , Akshara Kannan , Jack Keith , Abigail Parakoyi , MaryClare Pikus , Victoria Vance , Leena Ziane , Heather Brenhouse , Mikaela A. Laine , Rebecca M. Shansky
Pavlovian fear conditioning is a widely used tool that models associative learning in rodents. For decades the field has used predominantly male rodents and focused on a sole conditioned fear response: freezing. However, recent work from our lab and others has identified darting as a female-biased conditioned response, characterized by an escape-like movement across a fear conditioning chamber. It is also accompanied by a behavioral phenotype: Darters reliably show decreased freezing compared to Non-darters and males and reach higher velocities in response to the foot shock (“shock response”). However, the relationship between shock response and conditioned darting is not known. This study investigated if this link is due to differences in general processing of aversive stimuli between Darters, Non-darters and males. Across a variety of modalities, including corticosterone measures, the acoustic startle test, and sensitivity to thermal pain, Darters were found not to be more reactive or sensitive to aversive stimuli, and, in some cases, they appear less reactive to Non-darters and males. Analyses of cFos activity in regions involved in pain and fear processing following fear conditioning identified discrete patterns of expression among Darters, Non-darters, and males exposed to low and high intensity foot shocks. The results from these studies further our understanding of the differences between Darters, Non-darters and males and highlight the importance of studying individual differences in fear conditioning as indicators of fear state.
{"title":"Behavioral and neural correlates of diverse conditioned fear responses in male and female rats","authors":"Julia R. Mitchell , Lindsay Vincelette , Samantha Tuberman , Vivika Sheppard , Emmett Bergeron , Roberto Calitri , Rose Clark , Caitlyn Cody , Akshara Kannan , Jack Keith , Abigail Parakoyi , MaryClare Pikus , Victoria Vance , Leena Ziane , Heather Brenhouse , Mikaela A. Laine , Rebecca M. Shansky","doi":"10.1016/j.ynstr.2024.100675","DOIUrl":"10.1016/j.ynstr.2024.100675","url":null,"abstract":"<div><div>Pavlovian fear conditioning is a widely used tool that models associative learning in rodents. For decades the field has used predominantly male rodents and focused on a sole conditioned fear response: freezing. However, recent work from our lab and others has identified darting as a female-biased conditioned response, characterized by an escape-like movement across a fear conditioning chamber. It is also accompanied by a behavioral phenotype: Darters reliably show decreased freezing compared to Non-darters and males and reach higher velocities in response to the foot shock (“shock response”). However, the relationship between shock response and conditioned darting is not known. This study investigated if this link is due to differences in general processing of aversive stimuli between Darters, Non-darters and males. Across a variety of modalities, including corticosterone measures, the acoustic startle test, and sensitivity to thermal pain, Darters were found not to be more reactive or sensitive to aversive stimuli, and, in some cases, they appear less reactive to Non-darters and males. Analyses of cFos activity in regions involved in pain and fear processing following fear conditioning identified discrete patterns of expression among Darters, Non-darters, and males exposed to low and high intensity foot shocks. The results from these studies further our understanding of the differences between Darters, Non-darters and males and highlight the importance of studying individual differences in fear conditioning as indicators of fear state.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100675"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000717/pdfft?md5=4b62059f360b89745fab62771589e0b0&pid=1-s2.0-S2352289524000717-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142312606","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}
Pub Date : 2024-11-01Epub Date: 2024-11-07DOI: 10.1016/j.ynstr.2024.100688
Dan Zhao , Lu Zhang , Yang Yang
Both acute and chronic stress have significant impact on brain functions. The amygdala is essential in mediating stress responses, but how its transcriptomic dynamics change under stress remains elusive. To overcome the difficulties in detecting subtle stress-induced changes by evaluating total RNA using classic RNA sequencing, we conducted thiol-labeled RNA sequencing (SLAM-seq). We injected 4-thiouridine (4sU) into mouse amygdala followed by SLAM-seq to detect nascent mRNA induced by acute and chronic restraint stress, and found that SLAM-seq could label actively transcribed genes in the major neuronal and glial subtypes. Using SLAM-seq, we found that chronic stress led to higher turnover of a group of genes associated with myelination, and this finding is confirmed by immunostaining which showed increased myelination in the chronically stressed amygdala. Additionally, genes detected by SLAM-seq and RNA-seq only partially overlapped, suggesting that SLAM-seq and RNA-seq are complementary in identifying stress-responsive genes. By applying SLAM-seq in vivo, we obtained a rich dataset of genes with higher turnover in the amygdala under stress.
{"title":"Transcriptome dynamics in mouse amygdala under acute and chronic stress revealed by thiol-labeled RNA sequencing","authors":"Dan Zhao , Lu Zhang , Yang Yang","doi":"10.1016/j.ynstr.2024.100688","DOIUrl":"10.1016/j.ynstr.2024.100688","url":null,"abstract":"<div><div>Both acute and chronic stress have significant impact on brain functions. The amygdala is essential in mediating stress responses, but how its transcriptomic dynamics change under stress remains elusive. To overcome the difficulties in detecting subtle stress-induced changes by evaluating total RNA using classic RNA sequencing, we conducted thiol-labeled RNA sequencing (SLAM-seq). We injected 4-thiouridine (4sU) into mouse amygdala followed by SLAM-seq to detect nascent mRNA induced by acute and chronic restraint stress, and found that SLAM-seq could label actively transcribed genes in the major neuronal and glial subtypes. Using SLAM-seq, we found that chronic stress led to higher turnover of a group of genes associated with myelination, and this finding is confirmed by immunostaining which showed increased myelination in the chronically stressed amygdala. Additionally, genes detected by SLAM-seq and RNA-seq only partially overlapped, suggesting that SLAM-seq and RNA-seq are complementary in identifying stress-responsive genes. By applying SLAM-seq <em>in vivo</em>, we obtained a rich dataset of genes with higher turnover in the amygdala under stress.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100688"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660355","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}
Pub Date : 2024-11-01Epub Date: 2024-11-08DOI: 10.1016/j.ynstr.2024.100689
Alina Díez-Solinska , Zurine De Miguel , Garikoitz Azkona , Oscar Vegas
Social stress is the most significant source of chronic stress in humans and is commonly associated with health impairment. Individual differences in the behavioral coping responses to stress have been proposed to mediate the negative effects of stress on physical, behavioral and mental health. Animal models, particularly mice, offer valuable insights into the physiological and neurobiological correlates of behavioral coping strategies in response to chronic social stress. Here we aim to identify differences and similarities among stress protocols in mice, with particular attention to how neuroendocrine and/or behavioral responses vary according to different coping strategies, while highlighting the need for standardized approaches in future research. A systematic review was undertaken following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA statement). A total of 213 references were identified by electronic search, and after the screening, 18 articles were found to meet all the established criteria. We analyzed differences in the stress protocol, the characterization and classification of coping strategies and the physiological and behavioral differences according to coping. The results show that differences in behavioural expression under chronic social stress (coping) may also be associated with physiological differences and differential susceptibility to disease. However, this review also underlines the importance of a cautious interpretation of the results obtained. The lack of consistency in the nomenclature and procedures associated with the study of coping strategies for social stress, as well as the absence of a uniform classification, highlight the importance of using a common language when approaching the study of coping strategies. Thereby, this review encourages the development of a more defined method and criteria for assessing coping strategies, based on both behavioral and biological indicators.
{"title":"Behavioral coping with chronic defeat stress in mice: A systematic review of current protocols","authors":"Alina Díez-Solinska , Zurine De Miguel , Garikoitz Azkona , Oscar Vegas","doi":"10.1016/j.ynstr.2024.100689","DOIUrl":"10.1016/j.ynstr.2024.100689","url":null,"abstract":"<div><div>Social stress is the most significant source of chronic stress in humans and is commonly associated with health impairment. Individual differences in the behavioral coping responses to stress have been proposed to mediate the negative effects of stress on physical, behavioral and mental health. Animal models, particularly mice, offer valuable insights into the physiological and neurobiological correlates of behavioral coping strategies in response to chronic social stress. Here we aim to identify differences and similarities among stress protocols in mice, with particular attention to how neuroendocrine and/or behavioral responses vary according to different coping strategies, while highlighting the need for standardized approaches in future research. A systematic review was undertaken following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA statement). A total of 213 references were identified by electronic search, and after the screening, 18 articles were found to meet all the established criteria. We analyzed differences in the stress protocol, the characterization and classification of coping strategies and the physiological and behavioral differences according to coping. The results show that differences in behavioural expression under chronic social stress (coping) may also be associated with physiological differences and differential susceptibility to disease. However, this review also underlines the importance of a cautious interpretation of the results obtained. The lack of consistency in the nomenclature and procedures associated with the study of coping strategies for social stress, as well as the absence of a uniform classification, highlight the importance of using a common language when approaching the study of coping strategies. Thereby, this review encourages the development of a more defined method and criteria for assessing coping strategies, based on both behavioral and biological indicators.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100689"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660353","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}
Pub Date : 2024-11-01Epub Date: 2024-11-12DOI: 10.1016/j.ynstr.2024.100693
Eva C. Bach, Jeff L. Weiner
{"title":"Withdrawal notice to: “Elevated GABAergic neurotransmission prevents chronic intermittent ethanol induced hyperexcitability of intrinsic and extrinsic inputs to the ventral subiculum of female rats” [Neurobiol. Stress 32 (2024) 100665]","authors":"Eva C. Bach, Jeff L. Weiner","doi":"10.1016/j.ynstr.2024.100693","DOIUrl":"10.1016/j.ynstr.2024.100693","url":null,"abstract":"","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100693"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747043","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}
Pub Date : 2024-11-01Epub Date: 2024-10-22DOI: 10.1016/j.ynstr.2024.100683
E. Bączyńska , M. Zaręba-Kozioł , B. Ruszczycki , A. Krzystyniak , T. Wójtowicz , K. Bijata , B. Pochwat , M. Magnowska , M. Roszkowska , I. Figiel , J. Masternak , A. Pytyś , J. Dzwonek , R. Worch , K.H. Olszyński , A.D. Wardak , P. Szymczak , J. Labus , K. Radwańska , P. Jahołkowski , J. Włodarczyk
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.
{"title":"Stress resilience is an active and multifactorial process manifested by structural, functional, and molecular changes in synapses","authors":"E. Bączyńska , M. Zaręba-Kozioł , B. Ruszczycki , A. Krzystyniak , T. Wójtowicz , K. Bijata , B. Pochwat , M. Magnowska , M. Roszkowska , I. Figiel , J. Masternak , A. Pytyś , J. Dzwonek , R. Worch , K.H. Olszyński , A.D. Wardak , P. Szymczak , J. Labus , K. Radwańska , P. Jahołkowski , 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":"2024-11-01","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}
Pub Date : 2024-11-01Epub Date: 2024-10-16DOI: 10.1016/j.ynstr.2024.100680
Wei Fang , Xi Chen , Jufang He
The basolateral amygdala (BLA) hyperactivity has been implicated in the pathophysiology of anxiety disorders. We recently found that enhancing inhibitory transmission in BLA by chemo-genetic activation of local interneurons (INs) can reduce stress-induced anxiety-like behaviors in mice. Cholecystokinin interneurons (CCK-INs) are a major part of INs in BLA. It remains unknown whether CCK-INs modulated inhibition in BLA can mediate anxiety. In the present study, we found that BLA CCK-INs project extensively to most local excitatory neurons. Activating these CCK-INs using chemo-genetics and optogenetics can both effectively suppress electrical-induced neuronal activity within the BLA. Additionally, we observed that direct and sustained activation of CCK-INs within the BLA via chemo-genetics can mitigate stress-induced anxiety-like behaviors in mice and reduce stress-induced hyperactivity within the BLA itself. Furthermore, augmenting inhibitory plasticity within the BLA through a brief, 10-min high-frequency laser stimulation (HFLS) of CCK-INs also reduce stress-induced anxiety-like behaviors in mice. Collectively, these findings underscore the pivotal role of BLA CCK-IN-mediated inhibitory transmission and plasticity in modulating anxiety.
杏仁基底外侧(BLA)的过度活跃与焦虑症的病理生理学有关。我们最近发现,通过化学基因激活局部中间神经元(INs)来增强杏仁基底外侧的抑制性传导,可以减少小鼠由压力诱发的焦虑样行为。胆囊收缩素中间神经元(CCK-INs)是BLA中INs的主要组成部分。CCK-INs调节BLA中的抑制作用是否能介导焦虑仍是一个未知数。在本研究中,我们发现 BLA CCK-INs 广泛投射到大多数局部兴奋性神经元。利用化学遗传学和光遗传学激活这些 CCK-INs 都能有效抑制 BLA 内电诱导的神经元活动。此外,我们还观察到,通过化学遗传学直接、持续地激活 BLA 内的 CCK-INs 可以减轻应激诱导的小鼠焦虑样行为,并降低应激诱导的 BLA 自身的过度活跃性。此外,通过对CCK-INs进行10分钟的短暂高频激光刺激(HFLS)来增强BLA内的抑制可塑性,也能减少小鼠应激诱发的焦虑样行为。总之,这些发现强调了BLA CCK-IN介导的抑制性传递和可塑性在调节焦虑中的关键作用。
{"title":"Cholecystokinin-expressing interneurons mediated inhibitory transmission and plasticity in basolateral amygdala modulate stress-induced anxiety-like behaviors in mice","authors":"Wei Fang , Xi Chen , Jufang He","doi":"10.1016/j.ynstr.2024.100680","DOIUrl":"10.1016/j.ynstr.2024.100680","url":null,"abstract":"<div><div>The basolateral amygdala (BLA) hyperactivity has been implicated in the pathophysiology of anxiety disorders. We recently found that enhancing inhibitory transmission in BLA by chemo-genetic activation of local interneurons (INs) can reduce stress-induced anxiety-like behaviors in mice. Cholecystokinin interneurons (CCK-INs) are a major part of INs in BLA. It remains unknown whether CCK-INs modulated inhibition in BLA can mediate anxiety. In the present study, we found that BLA CCK-INs project extensively to most local excitatory neurons. Activating these CCK-INs using chemo-genetics and optogenetics can both effectively suppress electrical-induced neuronal activity within the BLA. Additionally, we observed that direct and sustained activation of CCK-INs within the BLA via chemo-genetics can mitigate stress-induced anxiety-like behaviors in mice and reduce stress-induced hyperactivity within the BLA itself. Furthermore, augmenting inhibitory plasticity within the BLA through a brief, 10-min high-frequency laser stimulation (HFLS) of CCK-INs also reduce stress-induced anxiety-like behaviors in mice. Collectively, these findings underscore the pivotal role of BLA CCK-IN-mediated inhibitory transmission and plasticity in modulating anxiety.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100680"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526670","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}
Pub Date : 2024-11-01Epub Date: 2024-09-18DOI: 10.1016/j.ynstr.2024.100674
Savannah Brannan, Lauren Garbe, Ben D. Richardson
Adverse childhood experiences have been associated with many neurodevelopmental and affective disorders including attention deficit hyperactivity disorder and generalized anxiety disorder, with more exposures increasing negative risk. Sex and genetic background are biological variables involved in adverse psychiatric outcomes due to early life trauma. Females in general have an increased prevalence of stress-related psychopathologies beginning after adolescence, indicative of adolescence being a female-specific sensitive period. To understand the underlying neuronal mechanisms potentially responsible for this relationship between genetic background, sex, stress/trauma, and cognitive/affective behaviors, we assessed behavioral and neuronal changes in a novel animal model of early life stress exposure. Male and female BALB/cJ mice that express elevated basal anxiety-like behaviors and differences in monoamine signaling-associated genes, were exposed to an early life variable stress protocol that combined deprivation in early life with unpredictability in adolescence. Stress exposure produced hyperlocomotion and attention deficits (5-choice serial reaction time task) in male and female mice along with female-specific increased anxiety-like behavior. These behavioral changes were paralleled by reduced excitability of locus coeruleus (LC) neurons, due to resting membrane potential hyperpolarization in males and a female-specific increase in action potential delay time. These data describe a novel interaction between sex, genetic background, and early life stress that results in behavioral changes in clinically relevant domains and potential underlying mechanistic lasting changes in physiological properties of neurons in the LC.
{"title":"Early life stress induced sex-specific changes in behavior is paralleled by altered locus coeruleus physiology in BALB/cJ mice","authors":"Savannah Brannan, Lauren Garbe, Ben D. Richardson","doi":"10.1016/j.ynstr.2024.100674","DOIUrl":"10.1016/j.ynstr.2024.100674","url":null,"abstract":"<div><div>Adverse childhood experiences have been associated with many neurodevelopmental and affective disorders including attention deficit hyperactivity disorder and generalized anxiety disorder, with more exposures increasing negative risk. Sex and genetic background are biological variables involved in adverse psychiatric outcomes due to early life trauma. Females in general have an increased prevalence of stress-related psychopathologies beginning after adolescence, indicative of adolescence being a female-specific sensitive period. To understand the underlying neuronal mechanisms potentially responsible for this relationship between genetic background, sex, stress/trauma, and cognitive/affective behaviors, we assessed behavioral and neuronal changes in a novel animal model of early life stress exposure. Male and female BALB/cJ mice that express elevated basal anxiety-like behaviors and differences in monoamine signaling-associated genes, were exposed to an early life variable stress protocol that combined deprivation in early life with unpredictability in adolescence. Stress exposure produced hyperlocomotion and attention deficits (5-choice serial reaction time task) in male and female mice along with female-specific increased anxiety-like behavior. These behavioral changes were paralleled by reduced excitability of locus coeruleus (LC) neurons, due to resting membrane potential hyperpolarization in males and a female-specific increase in action potential delay time. These data describe a novel interaction between sex, genetic background, and early life stress that results in behavioral changes in clinically relevant domains and potential underlying mechanistic lasting changes in physiological properties of neurons in the LC.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100674"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000705/pdfft?md5=619d3e35ab97587f0de791597ebd7efb&pid=1-s2.0-S2352289524000705-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142316279","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}
Pub Date : 2024-11-01Epub Date: 2024-10-17DOI: 10.1016/j.ynstr.2024.100679
Jen-Yin Goh , Patricia Rueda , Joy Taylor , Alex Rathbone , Daniel Scott , Christopher J. Langmead , Kevin C.F. Fone , Gregory D. Stewart , Madeleine V. King
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 (Hrh3, Snca and Sod1) and agonists or activators for products of six of these down-regulated DEGs (Chrm4, Klf2, Lrrk2, Nr4a1, Nr4a3 and Prkca). Some have already undergone pre-clinical and clinical evaluation, and studies with the remainder may be warranted. Changes to Hrh3, Sod1, Chrm4, Lrrk2, Nr4a1 and Prkca 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.
{"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 , Patricia Rueda , Joy Taylor , Alex Rathbone , Daniel Scott , Christopher J. Langmead , Kevin C.F. Fone , Gregory D. Stewart , 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":"2024-11-01","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}
Pub Date : 2024-11-01Epub Date: 2024-11-14DOI: 10.1016/j.ynstr.2024.100692
Jhoan S. Aguilar , Amy W. Lasek
Perineuronal nets (PNNs) are a special form of central nervous system extracellular matrix enriched in hyaluronan, chondroitin sulfate proteoglycans, tenascins, and link proteins that regulate synaptic plasticity. Most PNNs in the brain surround parvalbumin-expressing inhibitory interneurons, which tightly regulate excitatory/inhibitory balance and brain activity associated with optimal cognitive functioning. Alterations in PNNs have been observed in neurological diseases and psychiatric disorders, suggesting that they may be key contributors to the neuropathological progression and behavioral changes in these diseases. Alcohol use disorder (AUD), major depressive disorder (MDD), and chronic pain are highly comorbid conditions, and changes in PNNs have been observed in animal models of these disorders, as well as postmortem tissue from individuals diagnosed with AUD and MDD. This review focuses on the literature describing stress-, alcohol-, and pain-induced adaptations in PNNs, potential cellular contributors to altered PNNs, and the role of PNNs in behaviors related to these disorders. Medicines that can restore PNNs to a non-pathological state may be a novel therapeutic approach to treating chronic pain, AUD, and MDD.
{"title":"Modulation of stress-, pain-, and alcohol-related behaviors by perineuronal nets","authors":"Jhoan S. Aguilar , Amy W. Lasek","doi":"10.1016/j.ynstr.2024.100692","DOIUrl":"10.1016/j.ynstr.2024.100692","url":null,"abstract":"<div><div>Perineuronal nets (PNNs) are a special form of central nervous system extracellular matrix enriched in hyaluronan, chondroitin sulfate proteoglycans, tenascins, and link proteins that regulate synaptic plasticity. Most PNNs in the brain surround parvalbumin-expressing inhibitory interneurons, which tightly regulate excitatory/inhibitory balance and brain activity associated with optimal cognitive functioning. Alterations in PNNs have been observed in neurological diseases and psychiatric disorders, suggesting that they may be key contributors to the neuropathological progression and behavioral changes in these diseases. Alcohol use disorder (AUD), major depressive disorder (MDD), and chronic pain are highly comorbid conditions, and changes in PNNs have been observed in animal models of these disorders, as well as postmortem tissue from individuals diagnosed with AUD and MDD. This review focuses on the literature describing stress-, alcohol-, and pain-induced adaptations in PNNs, potential cellular contributors to altered PNNs, and the role of PNNs in behaviors related to these disorders. Medicines that can restore PNNs to a non-pathological state may be a novel therapeutic approach to treating chronic pain, AUD, and MDD.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"33 ","pages":"Article 100692"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706092","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}
Pub Date : 2024-11-01Epub Date: 2024-10-18DOI: 10.1016/j.ynstr.2024.100682
Zihan Tang , Yadong Liu , Xiaolin Zhao , Weiyu Hu , Mengning Zhang , Yipeng Ren , Zhenni Wei , Juan Yang
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 (r = -0.268, p = 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], p = 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.
{"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 , Yadong Liu , Xiaolin Zhao , Weiyu Hu , Mengning Zhang , Yipeng Ren , Zhenni Wei , 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":"2024-11-01","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}