{"title":"Predator odor stress reactivity, alcohol drinking and the endocannabinoid system","authors":"Laura C. Ornelas , Joyce Besheer","doi":"10.1016/j.ynstr.2024.100634","DOIUrl":"https://doi.org/10.1016/j.ynstr.2024.100634","url":null,"abstract":"<div><p>Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid and individual differences in response to stress suggest resilient and susceptible populations. Using animal models to target neurobiological mechanisms associated with individual variability in stress coping responses and the relationship with subsequent increases in alcohol consumption has important implications for the field of traumatic stress and alcohol disorders. The current review discusses the unique advantages of utilizing predator odor stressor exposure models, specifically using 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) on better understanding PTSD pathophysiology and neurobiological mechanisms associated with stress reactivity and subsequent increases in alcohol drinking. Furthermore, there has been increasing interest regarding the role of the endocannabinoid system in modulating behavioral responses to stress with an emphasis on stress coping and individual differences in stress-susceptibility. Therefore, the current review focuses on the topic of endocannabinoid modulation of stress reactive behaviors during and after exposure to a predator odor stressor, with implications on modulating distinctly different behavioral coping strategies.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"30 ","pages":"Article 100634"},"PeriodicalIF":5.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000304/pdfft?md5=16a71c61b882ebcace38c109e1ef6837&pid=1-s2.0-S2352289524000304-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140535647","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}
Chao Wang , Ningyuan Li , Yuqi Feng , Siqi Sun , Jingtong Rong , Xin-hui Xie , Shuxian Xu , Zhongchun Liu
{"title":"Effects of autotaxin and lysophosphatidic acid deficiencies on depression-like behaviors in mice exposed to chronic unpredictable mild stress","authors":"Chao Wang , Ningyuan Li , Yuqi Feng , Siqi Sun , Jingtong Rong , Xin-hui Xie , Shuxian Xu , Zhongchun Liu","doi":"10.1016/j.ynstr.2024.100632","DOIUrl":"https://doi.org/10.1016/j.ynstr.2024.100632","url":null,"abstract":"<div><p>The involvement of lipids in the mechanism of depression has triggered extensive discussions. Earlier studies have identified diminished levels of lysophosphatidic acid (LPA) and autotaxin (ATX) in individuals experiencing depression. However, the exact significance of this phenomenon in relation to depression remains inconclusive. This study seeks to explore the deeper implications of these observations. We assessed alterations in ATX and LPA in both the control group and the chronic unpredictable mild stress (CUMS) model group. Additionally, the impact of ATX adeno-associated virus (AAV-ATX) injection into the hippocampus was validated through behavioral tests in CUMS-exposed mice. Furthermore, we probed the effects of LPA on synapse-associated proteins both in HT22 cells and within the mouse hippocampus. The mechanisms underpinning the LPA-triggered shifts in protein expression were further scrutinized. Hippocampal tissues were augmented with ATX to assess its potential to alleviate depression-like behavior by modulating synaptic-related proteins. Our findings suggest that the decrement in ATX and LPA levels alters the expression of proteins associated with synaptic plasticity <em>in vitro</em> and <em>in vivo</em>, such as synapsin-I (SYN), synaptophysin (SYP), and brain-derived neurotrophic factor (BDNF). Moreover, we discerned a role for the ERK/CREB signaling pathway in mediating the effects of ATX and LPA. Importantly, strategic supplementation of ATX effectively mitigated depression-like behaviors. This study indicates that the ATX-LPA pathway may influence depression-like behaviors by modulating synaptic plasticity in the brains of CUMS-exposed mice. These insights augment our understanding of depression's potential pathogenic mechanism in the context of lipid metabolism and propose promising therapeutic strategies for ameliorating the disease.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"30 ","pages":"Article 100632"},"PeriodicalIF":5.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000286/pdfft?md5=bb6f02b88dbf02788d634a75b6124607&pid=1-s2.0-S2352289524000286-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140345221","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}
Alice Sanson , Paula Krieg , Milena M. Schramm , Kerstin Kellner , Rodrigue Maloumby , Stefanie M. Klampfl , Paula J. Brunton , Oliver J. Bosch
{"title":"CRF binding protein activity in the hypothalamic paraventricular nucleus is essential for stress adaptations and normal maternal behaviour in lactating rats","authors":"Alice Sanson , Paula Krieg , Milena M. Schramm , Kerstin Kellner , Rodrigue Maloumby , Stefanie M. Klampfl , Paula J. Brunton , Oliver J. Bosch","doi":"10.1016/j.ynstr.2024.100631","DOIUrl":"https://doi.org/10.1016/j.ynstr.2024.100631","url":null,"abstract":"<div><p>To ensure the unrestricted expression of maternal behaviour peripartum, activity of the corticotropin-releasing factor (CRF) system needs to be minimised. CRF binding protein (CRF-BP) might be crucial for this adaptation, as its primary function is to sequester freely available CRF and urocortin1, thereby dampening CRF receptor (CRF-R) signalling. So far, the role of CRF-BP in the maternal brain has barely been studied, and a potential role in curtailing activation of the stress axis is unknown.</p><p>We studied gene expression for CRF-BP and both CRF-R within the paraventricular nucleus (PVN) of the hypothalamus. In lactating rats, <em>Crh-bp</em> expression in the parvocellular PVN was significantly higher and <em>Crh-r1</em> expression in the PVN significantly lower compared to virgin rats. Acute CRF-BP inhibition in the PVN with infusion of CRF(6–33) increased basal plasma corticosterone concentrations under unstressed conditions in dams. Furthermore, while acute intra-PVN infusion of CRF increased corticosterone secretion in virgin rats, it was ineffective in vehicle (VEH)-pre-treated lactating rats, probably due to a buffering effect of CRF-BP. Indeed, pre-treatment with CRF(6–33) reinstated a corticosterone response to CRF in lactating rats, highlighting the critical role of CRF-BP in maintaining attenuated stress reactivity in lactation. To our knowledge, this is the first study linking hypothalamic CRF-BP activity to hypothalamic-pituitary-adrenal axis regulation in lactation. In terms of behaviour, acute CRF-BP inhibition in the PVN under non-stress conditions reduced blanket nursing 60 min and licking/grooming 90 min after infusion compared to VEH-treated rats, while increasing maternal aggression towards an intruder. Lastly, chronic intra-PVN inhibition of CRF-BP strongly reduced maternal aggression, with modest effects on maternal motivation and care.</p><p>Taken together, intact activity of the CRF-BP in the PVN during the postpartum period is essential for the dampened responsiveness of the stress axis, as well as for the full expression of appropriate maternal behaviour.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"30 ","pages":"Article 100631"},"PeriodicalIF":5.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000274/pdfft?md5=01b24c39ff506e14f0e16b63b2cdff87&pid=1-s2.0-S2352289524000274-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140345438","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}
Dageon Yeo , Seulgi Lee , Haemi Choi , Min-Hyeon Park , Bumhee Park
{"title":"Emotional abuse mediated by negative automatic thoughts impacts functional connectivity during adolescence","authors":"Dageon Yeo , Seulgi Lee , Haemi Choi , Min-Hyeon Park , Bumhee Park","doi":"10.1016/j.ynstr.2024.100623","DOIUrl":"10.1016/j.ynstr.2024.100623","url":null,"abstract":"<div><h3>Background</h3><p>Emotional abuse during childhood and adolescence is thought to be associated with the brain; however, the neural mechanism underlying the cognitive process remains unknown. Therefore, we aimed to investigate the mediating effect of negative automatic thoughts on the relationship between emotional abuse and resting-state functional connectivity (rsFC) during adolescence.</p></div><div><h3>Method</h3><p>Our community sample included 54 adolescents aged 13–17 years in the statistical analysis. Resting-state functional and structural magnetic resonance imaging (MRI) was performed, while emotional abuse and negative automatic thoughts were assessed using self-reported scales. A mediation analysis was used to assess the contributions of early traumatic events and negative automatic thoughts to resting functional connectivity.</p></div><div><h3>Result</h3><p>Higher negative automatic thoughts were associated with lower connectivity in the context of greater emotional abuse (i.e., suppression effect). Thus, the relationships between emotional abuse and connectivity in the precuneus (pCun)-medial prefrontal cortex, parahippocampal cortex-extrastriate cortex, and temporal cortex-temporal pole were decreased by negative automatic thoughts. In contrast, functional connections in the pCun-pCun, pCun-precuneus/posterior cingulate cortex, and nucleus accumbens-somatomotor areas were strongly mediated when emotionally abused adolescents reported a high tendency for negative automatic thoughts.</p></div><div><h3>Conclusion</h3><p>Negative automatic thoughts strengthened the relationship between emotional abuse and rsFC. These findings highlight the underlying cognitive processing of the traumatic event-neural system, supporting the use of cognitive therapy for post-traumatic symptoms.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"30 ","pages":"Article 100623"},"PeriodicalIF":5.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000195/pdfft?md5=fd150258965cc78c588b6f633393a85c&pid=1-s2.0-S2352289524000195-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140278995","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":"A gut (microbiome) feeling about addiction: Interactions with stress and social systems","authors":"Rubén García-Cabrerizo , John F. Cryan","doi":"10.1016/j.ynstr.2024.100629","DOIUrl":"10.1016/j.ynstr.2024.100629","url":null,"abstract":"<div><p>In recent years, an increasing attention has given to the intricate and diverse connection of microorganisms residing in our gut and their impact on brain health and central nervous system disease. There has been a shift in mindset to understand that drug addiction is not merely a condition that affects the brain, it is now being recognized as a disorder that also involves external factors such as the intestinal microbiota, which could influence vulnerability and the development of addictive behaviors. Furthermore, stress and social interactions, which are closely linked to the intestinal microbiota, are powerful modulators of addiction. This review delves into the mechanisms through which the microbiota-stress-immune axis may shape drug addiction and social behaviors. This work integrates preclinical and clinical evidence that demonstrate the bidirectional communication between stress, social behaviors, substance use disorders and the gut microbiota, suggesting that gut microbes might modulate social stress having a significance in drug addiction.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"30 ","pages":"Article 100629"},"PeriodicalIF":5.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000250/pdfft?md5=9ba60fdcad00dec74375cbdfd4d053e9&pid=1-s2.0-S2352289524000250-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140153852","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}
M.K.P. Joyce, S. Yang, K. Morin, A. Duque, J. Arellano, D. Datta, M. Wang, A.F.T. Arnsten
{"title":"β1-adrenoceptor expression on GABAergic interneurons in primate dorsolateral prefrontal cortex: potential role in stress-induced cognitive dysfunction","authors":"M.K.P. Joyce, S. Yang, K. Morin, A. Duque, J. Arellano, D. Datta, M. Wang, A.F.T. Arnsten","doi":"10.1016/j.ynstr.2024.100628","DOIUrl":"10.1016/j.ynstr.2024.100628","url":null,"abstract":"<div><p>Uncontrollable stress exposure impairs working memory and reduces the firing of dorsolateral prefrontal cortex (dlPFC) “Delay cells”, involving high levels of norepinephrine and dopamine release. Previous work has focused on catecholamine actions on dlPFC pyramidal cells, but inhibitory interneurons may contribute as well. The current study combined immunohistochemistry and multi-scale microscopy with iontophoretic physiology and behavioral analyses to examine the effects of beta1-noradrenergic receptors (β1-ARs) on inhibitory neurons in layer III dlPFC. We found β1-AR robustly expressed on different classes of inhibitory neurons labeled by the calcium-binding proteins calbindin (CB), calretinin (CR), and parvalbumin (PV). Immunoelectron microscopy confirmed β1-AR expression on the plasma membrane of PV-expressing dendrites. PV interneurons can be identified as fast-spiking (FS) in physiological recordings, and thus were studied in macaques performing a working memory task. Iontophoresis of a β1-AR agonist had a mixed effect, increasing the firing of a subset and decreasing the firing of others, likely reflecting loss of firing of the entire microcircuit. This loss of overall firing likely contributes to impaired working memory during stress, as pretreatment with the selective β1-AR antagonist, nebivolol, prevented stress-induced working memory deficits. Thus, selective β1-AR antagonists may be helpful in treating stress-related disorders.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"30 ","pages":"Article 100628"},"PeriodicalIF":5.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000249/pdfft?md5=46d28d2d6f2a21c3801598b596f48a07&pid=1-s2.0-S2352289524000249-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140154008","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}
Cuihong Jia, W. Drew Gill, Chiharu Lovins, Russell W. Brown , Theo Hagg
{"title":"Astrocyte focal adhesion kinase reduces passive stress coping by inhibiting ciliary neurotrophic factor only in female mice","authors":"Cuihong Jia, W. Drew Gill, Chiharu Lovins, Russell W. Brown , Theo Hagg","doi":"10.1016/j.ynstr.2024.100621","DOIUrl":"https://doi.org/10.1016/j.ynstr.2024.100621","url":null,"abstract":"<div><p>Astrocytes have been implicated in stress responses and produce ciliary neurotrophic factor (CNTF), which we have shown in the mouse medial amygdala (MeA) to promote passive stress coping response only in females. Pharmacological inhibition of focal adhesion kinase (FAK) upregulates CNTF expression. Here, we found that inducible knockout of FAK in astrocytes or systemic treatment with an FAK inhibitor increased passive coping behavior, i.e., immobility, in an acute forced swim stress test in female, but not male, mice. Strikingly, four weeks of chronic unpredictable stress (CUS) did not further increase passive coping in female astrocytic FAK knockout mice, whereas it exacerbated it in female wildtype mice and male mice of both genotypes. These data suggest that astrocyte FAK inhibition is required for chronic stress-induced passive coping in females. Indeed, CUS reduced phospho-FAK and increased CNTF in the female MeA. Progesterone treatment after ovariectomy activated amygdala FAK and alleviated ovariectomy-induced passive coping in wildtype, but not astrocytic FAK knockout females. This suggests that progesterone-mediated activation of FAK in astrocytes reduces female stress responses. Finally, astrocytic FAK knockout or FAK inhibitor treatment increased CNTF expression in the MeA of both sexes, although not in the hippocampus. As mentioned, MeA CNTF promotes stress responses only in females, which may explain the female-specific role of astrocytic FAK inhibition. Together, this study reveals a novel female-specific progesterone-astrocytic FAK pathway that counteracts CNTF-mediated stress responses and points to opportunities for developing treatments for stress-related disorders in women.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"30 ","pages":"Article 100621"},"PeriodicalIF":5.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000171/pdfft?md5=b3c9f46d5085d9d0c7b70b4812056a13&pid=1-s2.0-S2352289524000171-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140134310","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}
Guopeng Chen , Yuhui Zhang , Ruiling Li , Liuyin Jin , Keke Hao , Jingtong Rong , Hao Duan , Yiwei Du , Lihua Yao , Dan Xiang , Zhongchun Liu
{"title":"Environmental enrichment attenuates depressive-like behavior in maternal rats by inhibiting neuroinflammation and apoptosis and promoting neuroplasticity","authors":"Guopeng Chen , Yuhui Zhang , Ruiling Li , Liuyin Jin , Keke Hao , Jingtong Rong , Hao Duan , Yiwei Du , Lihua Yao , Dan Xiang , Zhongchun Liu","doi":"10.1016/j.ynstr.2024.100624","DOIUrl":"https://doi.org/10.1016/j.ynstr.2024.100624","url":null,"abstract":"<div><p>Gestational stress can exacerbate postpartum depression (PPD), for which treatment options remain limited. Environmental enrichment (EE) may be a therapeutic intervention for neuropsychiatric disorders, including depression, but the specific mechanisms by which EE might impact PPD remain unknown. Here we examined the behavioral, molecular, and cellular impact of EE in a stable PPD model in rats developed through maternal separation (MS). Maternal rats subjected to MS developed depression-like behavior and cognitive dysfunction together with evidence of significant neuroinflammation including microglia activation, neuronal apoptosis, and impaired synaptic plasticity. Expanding the duration of EE to throughout pregnancy and lactation, we observed an EE-associated reversal of MS-induced depressive phenotypes, inhibition of neuroinflammation and neuronal apoptosis, and improvement in synaptic plasticity in maternal rats. Thus, EE effectively alleviates neuroinflammation, neuronal apoptosis, damage to synaptic plasticity, and consequent depression-like behavior in mother rats experiencing MS-induced PPD, paving the way for new preventive and therapeutic strategies for PPD.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"30 ","pages":"Article 100624"},"PeriodicalIF":5.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000201/pdfft?md5=a7e60b7699895e0d532c22cf951219f7&pid=1-s2.0-S2352289524000201-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137706","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}
Guangya Wang , Jun Tang , Zhouqian Yin , Siyu Yu , Xindi Shi , Xiurong Hao , Zhudele Zhao , Yafeng Pan , Shijia Li
{"title":"The neurocomputational signature of decision-making for unfair offers in females under acute psychological stress","authors":"Guangya Wang , Jun Tang , Zhouqian Yin , Siyu Yu , Xindi Shi , Xiurong Hao , Zhudele Zhao , Yafeng Pan , Shijia Li","doi":"10.1016/j.ynstr.2024.100622","DOIUrl":"10.1016/j.ynstr.2024.100622","url":null,"abstract":"<div><p>Stress is a crucial factor affecting social decision-making. However, its impacts on the behavioral and neural processes of females’ unfairness decision-making remain unclear. Combining computational modeling and functional near-infrared spectroscopy (fNIRS), this study attempted to illuminate the neurocomputational signature of unfairness decision-making in females. We also considered the effect of trait stress coping styles. Forty-four healthy young females (20.98 ± 2.89 years) were randomly assigned to the stress group (<em>n</em> = 21) and the control group (<em>n</em> = 23). Acute psychosocial stress was induced by the Trier Social Stress Test (TSST), and participants then completed the one-shot ultimatum game (UG) as responders. The results showed that acute psychosocial stress reduced the adaptability to fairness and lead to more random decision-making responses. Moreover, in the stress group, a high level of negative coping style predicted more deterministic decision. fNIRS results showed that stress led to an increase of oxy-hemoglobin (HbO) peak in the right temporoparietal junction (rTPJ), while decreased the activation of left middle temporal gyrus (lMTG) when presented the moderately unfair (MU) offers. This signified more involvement of the mentalization and the inhibition of moral processing. Moreover, individuals with higher negative coping scores showed more deterministic decision behaviors under stress. Taken together, our study emphasizes the role of acute psychosocial stress in affecting females’ unfairness decision-making mechanisms in social interactions, and provides evidences for the “tend and befriend” pattern based on a cognitive neuroscience perspec</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"30 ","pages":"Article 100622"},"PeriodicalIF":5.0,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000183/pdfft?md5=ae40407ebdc37063e7971273498b678a&pid=1-s2.0-S2352289524000183-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140092204","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}
Gisela Armada , Susana Roque , Cláudia Serre-Miranda , Liliana Ferreira , Ana Vale , Ana João Rodrigues , Wanjin Hong , Margarida Correia-Neves , Neide Vieira
{"title":"SNX27: A trans-species cognitive modulator with implications for anxiety and stress susceptibility","authors":"Gisela Armada , Susana Roque , Cláudia Serre-Miranda , Liliana Ferreira , Ana Vale , Ana João Rodrigues , Wanjin Hong , Margarida Correia-Neves , Neide Vieira","doi":"10.1016/j.ynstr.2024.100619","DOIUrl":"10.1016/j.ynstr.2024.100619","url":null,"abstract":"<div><p>Sorting Nexin 27 (SNX27) is a brain-enriched endosome-associated cargo adaptor that shapes excitatory control, being relevant for cognitive and reward processing, and for several neurological conditions. Despite this, SNX27's role in the nervous system remains poorly explored. To further understand SNX27 function, we performed an extensive behavioral characterization comprising motor, cognitive and emotional dimensions of SNX27<sup>+/−</sup> mice. Furthermore, attending on the recently described association between SNX27 function and cellular stress signaling mechanisms <em>in vitro</em>, we explored SNX27-stress interplay using a <em>Caenorhabditis elegans Δsnx-27</em> mutant and wild-type (WT) rodents after stress exposure.</p><p>SNX27<sup>+/−</sup> mice, as <em>C. elegans Δsnx-27</em> mutants, present cognitive impairments, highlighting a conserved role for SNX27 in cognitive modulation across species. Interestingly, SNX27 downmodulation leads to anxiety-like behavior in mice evaluated in the Elevated Plus Maze (EPM). This anxious phenotype is associated with increased dendritic complexity of the bed nucleus of the stria terminalis (BNST) neurons, and increased complexity of the basolateral amygdala (BLA) pyramidal neurons. These findings highlight the still unknown role of SNX27 in anxiety regulation.</p><p>Moreover, we uncovered a direct link between SNX27 dysfunction and stress susceptibility in <em>C. elegans</em> and found that stress-exposed rodents display decreased SNX27 levels in stress-susceptible brain regions.</p><p>Altogether, we provided new insights on SNX27's relevance in anxiety-related behaviors and neuronal structure in stress-associated brain regions.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"30 ","pages":"Article 100619"},"PeriodicalIF":5.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000158/pdfft?md5=80925083eafe26aeb3cf8789dfbb0c8d&pid=1-s2.0-S2352289524000158-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140092692","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}