Pub Date : 2024-11-01DOI: 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.
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Pub Date : 2024-11-01DOI: 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 : 2024-11-01DOI: 10.1016/j.ynstr.2024.100694
Robert J. Aukema , Gavin N. Petrie , Samantha L. Baglot , Nicholas W. Gilpin , Matthew N. Hill
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 BLACRHR1 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.
尽管杏仁基底外侧(BLA)和促肾上腺皮质激素释放激素受体 I 型(CRHR1)信号传导都是应激反应的核心,但 CRHR1 在杏仁基底外侧的空间和回路特异性分布尚未得到高分辨率的鉴定。我们利用转基因雄性和雌性 CRHR1-Cre-tdTomato 大鼠绘制了 BLACRHR1 神经元分布的地形图,并确定它们是否被急性应激激活。此外,我们还以投射到杏仁核中枢(CeA)和伏隔核(NAc)的BLA回路为模型,测试了CRHR1在BLA回路中的特异性表达。我们得出了几个重要发现。首先,CRHR1在杏仁核外侧和BLA尾部的表达最强。第二,急性束缚应激增加了CRHR1神经元的FOS表达,应激诱导的激活在BLA的内侧亚区尤其强烈。第三,应激明显增加了BLA-NAc上的FOS表达,但没有增加BLA-CeA突起上的FOS表达,而且男性的BLA-NAc激活比女性更强。最后,CRHR1在一部分BLA-CeA和BLA-NAc投射神经元上表达。总之,这拓展了我们对急性应激后BLA分子和回路特异性激活模式的理解。
{"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 , Gavin N. Petrie , Samantha L. Baglot , Nicholas W. Gilpin , 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<sup>CRHR1</sup> 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}
Pub Date : 2024-11-01DOI: 10.1016/j.ynstr.2024.100686
Lars Wilmes , Valentina Caputi , Thomaz F.S. Bastiaanssen , James M. Collins , Fiona Crispie , Paul D. Cotter , Timothy G. Dinan , John F. Cryan , Gerard Clarke , Siobhain M. O'Mahony
Background
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.
Methods
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.
Results
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.
Conclusion
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.
{"title":"Sex specific gut-microbiota signatures of resilient and comorbid gut-brain phenotypes induced by early life stress","authors":"Lars Wilmes , Valentina Caputi , Thomaz F.S. Bastiaanssen , James M. Collins , Fiona Crispie , Paul D. Cotter , Timothy G. Dinan , John F. Cryan , Gerard Clarke , 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}
Pub Date : 2024-11-01DOI: 10.1016/j.ynstr.2024.100690
Danina Evertse , Pilar Alves-Martinez , Giulia Treccani , Marianne B. Müller , Frank J. Meye , Michael A. van der Kooij
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 ad libitum 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.
{"title":"Transient impact of chronic social stress on effort-based reward motivation in non-food restricted mice: Involvement of corticosterone","authors":"Danina Evertse , Pilar Alves-Martinez , Giulia Treccani , Marianne B. Müller , Frank J. Meye , 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}
Pub Date : 2024-11-01DOI: 10.1016/j.ynstr.2024.100691
Carlos Ventura-Bort , Janine Wirkner , Julia Wendt , Lars Schwabe , Florin Dolcos , Alfons O. Hamm , Mathias Weymar
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.
虽然压力荷尔蒙系统在单一事件(尤其是情绪事件)记忆中的中介作用已得到公认,但人们对压力对相关情境信息记忆(源记忆)的影响却知之甚少。在这里,我们研究了急性应激对情绪情境源记忆神经基础的影响。受试者在编码与愉快、中性或不愉快背景配对的对象之前,会接受压力或对照操作。一周后,对项目记忆和情境源记忆进行测试。急性应激以相反的方式调节了物品记忆和背景来源记忆的神经特征:在检索物品时,应激参与者的楔前叶和内侧前额叶皮层(mPFC)显示出更大的激活,而检索背景不愉快信息时,角回(AG)和mPFC的激活较低。此外,跨区域表征相似性分析表明,压力还降低了 AG 和 mPFC 中先前编码的物体/不愉快背景配对的视觉皮层表征的记忆恢复。这些结果表明,编码前的压力诱导会增加记忆相关区域对单个项目的活动,但在检索背景不愉快信息时会降低这些区域的活动。我们的研究结果为压力对项目记忆和情境源记忆的分离效应提供了新的见解,这可能对压力相关障碍具有临床意义。
{"title":"Opposing effects of pre-encoding stress on neural substrates of item and emotional contextual source memory retrieval","authors":"Carlos Ventura-Bort , Janine Wirkner , Julia Wendt , Lars Schwabe , Florin Dolcos , Alfons O. Hamm , 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}
Pub Date : 2024-10-24DOI: 10.1016/j.ynstr.2024.100685
Linping Wang , Weiyao Wang , Yingshun Li , Hua Jin , Bin Xiao , Qinghua Jin
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.
{"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 , Weiyao Wang , Yingshun Li , Hua Jin , Bin Xiao , 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-) Ca<sup>2+</sup>/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}
Pub Date : 2024-10-24DOI: 10.1016/j.ynstr.2024.100684
Mark K. Greenwald , Eric A. Woodcock , Tabitha E.H. Moses , Leslie H. Lundahl
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; t = 0 min) then hydrocortisone (0, 20, 40-mg; t = 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.
{"title":"Basal cortisol level modulates stress-induced opioid-seeking behavior","authors":"Mark K. Greenwald , Eric A. Woodcock , Tabitha E.H. Moses , 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 α<sub>2</sub>-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}
Pub 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":"2024-10-22","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}
Pub 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":"2024-10-18","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}