Neurobiology of Stress最新文献

{"title":"Neural correlates of stress-reactive rumination in depression – The role of childhood trauma and social anxiety","authors":"David Rosenbaum ,&nbsp;Isabell Int-Veen ,&nbsp;Hendrik Laicher ,&nbsp;Leonie Woloszyn ,&nbsp;Ariane Wiegand ,&nbsp;Sandra Ladegast ,&nbsp;Ute Eßer ,&nbsp;Agnes Kroczek ,&nbsp;Daniel Sippel ,&nbsp;Sebastian Menkor ,&nbsp;Glenn Lawyer ,&nbsp;Francesco Albasini ,&nbsp;Christian Frischholz ,&nbsp;Rainald Mössner ,&nbsp;Vanessa Nieratschker ,&nbsp;Elisabeth J. Leehr ,&nbsp;Julian Rubel ,&nbsp;Andreas J. Fallgatter ,&nbsp;Ann-Christine Ehlis","doi":"10.1016/j.ynstr.2024.100640","DOIUrl":"10.1016/j.ynstr.2024.100640","url":null,"abstract":"<div><p>Recent work showed an association of prefrontal dysfunctions in patients with Major Depressive Disorder (MDD) and social stress induced rumination. However, up to date it is unclear which etiological features of MDD might cause prefrontal dysfunctions. In the study at hand, we aimed to replicate recent findings, that showed prefrontal activation alterations during the Trier Social Stress Test (TSST) and subsequently increased stress-reactive rumination in MDD compared to healthy controls. Moreover, we aimed to explore the role of adverse childhood experiences and other clinical variables in this relationship. N = 55 patients currently suffering from MDD and n = 42 healthy controls (HC) underwent the TSST, while cortical activity in areas of the Cognitive Control Network (CCN) was measured via functional near-infrared spectroscopy (fNIRS). The TSST successfully induced a stress reaction (physiologically, as well as indicated by subjective stress ratings) and state rumination in all subjects with moderate to large effect sizes. In comparison to HC, MDD patients showed elevated levels of state rumination with large effect sizes, as well as a typical pattern of reduced cortical oxygenation during stress in the CCN with moderate effect sizes. Self-reported emotional abuse and social anxiety were moderately positively associated with increased stress-reactive rumination. Within the MDD sample, emotional abuse was negatively and social anxiety positively associated with cortical oxygenation within the CCN with moderate to large effect sizes. In conclusion, our results replicate previous findings on MDD-associated prefrontal hypoactivity during stress and extends the research toward specific subtypes of depression.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"31 ","pages":"Article 100640"},"PeriodicalIF":5.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000365/pdfft?md5=a1d875ff9ce6b9cc8590e86b1628ebad&pid=1-s2.0-S2352289524000365-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141030664","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":"Toll-like receptor 7: A novel neuroimmune target to reduce excessive alcohol consumption","authors":"Ruth L. Allard ,&nbsp;Jody Mayfield ,&nbsp;Riccardo Barchiesi ,&nbsp;Nihal A. Salem ,&nbsp;R. Dayne Mayfield","doi":"10.1016/j.ynstr.2024.100639","DOIUrl":"https://doi.org/10.1016/j.ynstr.2024.100639","url":null,"abstract":"<div><p>Toll-like receptors (TLRs) are a family of innate immune receptors that recognize molecular patterns in foreign pathogens and intrinsic danger/damage signals from cells. TLR7 is a nucleic acid sensing endosomal TLR that is activated by single-stranded RNAs from microbes or by small noncoding RNAs that act as endogenous ligands. TLR7 signals through the MyD88 adaptor protein and activates the transcription factor interferon regulatory factor 7 (IRF7). TLR7 is found throughout the brain and is highly expressed in microglia, the main immune cells of the brain that have also been implicated in alcohol drinking in mice. Upregulation of <em>TLR7</em> mRNA and protein has been identified in postmortem hippocampus and cortex from AUD subjects that correlated positively with lifetime consumption of alcohol. Similarly, <em>Tlr7</em> and downstream signaling genes were upregulated in rat hippocampal and cortical slice cultures after chronic alcohol exposure and in these regions after chronic binge-like alcohol treatment in mice. In addition, repeated administration of the synthetic TLR7 agonists imiquimod (R837) or resiquimod (R848) increased voluntary alcohol drinking in different rodent models and produced sustained upregulation of IRF7 in the brain. These findings suggest that chronic TLR7 activation may drive excessive alcohol drinking. In the brain, this could occur through increased levels of endogenous TLR7 activators, like microRNAs and Y RNAs. This review explores chronic TLR7 activation as a pathway of dysregulated neuroimmune signaling in AUD and the endogenous small RNA ligands in the brain that could perpetuate innate immune responses and escalate alcohol drinking.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"31 ","pages":"Article 100639"},"PeriodicalIF":5.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000353/pdfft?md5=67aab2ef581063a7715f2b1eae5940b8&pid=1-s2.0-S2352289524000353-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140880464","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":"Subcallosal area 25: Its responsivity to the stress hormone cortisol and its opposing effects on appetitive motivation in marmosets","authors":"Rana Banai Tizkar,&nbsp;Lauren McIver,&nbsp;Christian Michael Wood ,&nbsp;Angela Charlotte Roberts","doi":"10.1016/j.ynstr.2024.100637","DOIUrl":"https://doi.org/10.1016/j.ynstr.2024.100637","url":null,"abstract":"<div><p>Aberrant activity in caudal subcallosal anterior cingulate cortex (scACC) is implicated in depression and anxiety symptomatology, with its normalisation a putative biomarker of successful treatment response. The function of scACC in emotion processing and mental health is not fully understood despite its known influence on stress-mediated processes through its rich expression of mineralocorticoid and glucocorticoid receptors. Here we examine the causal interaction between area 25 within scACC (scACC-25) and the stress hormone, cortisol, in the context of anhedonia and anxiety-like behaviour. In addition, the overall role of scACC-25 in hedonic capacity and motivation is investigated under transient pharmacological inactivation and overactivation. The results suggest that a local increase of cortisol in scACC-25 shows a rapid induction of anticipatory anhedonia and increased responsiveness to uncertain threat. Separate inactivation and overactivation of scACC-25 increased and decreased motivation and hedonic capacity, respectively, likely through different underlying mechanisms. Together, these data show that area scACC-25 has a causal role in consummatory and motivational behaviour and produces rapid responses to the stress hormone cortisol, that mediates anhedonia and anxiety-like behaviour.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"31 ","pages":"Article 100637"},"PeriodicalIF":5.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S235228952400033X/pdfft?md5=b1fb4e3f9090692cab92695efec04768&pid=1-s2.0-S235228952400033X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825298","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":"Corrigendum to “Cross-sectional study of retrospective self-reported childhood emotional neglect and inhibitory neurometabolite levels in the pregenual anterior cingulate cortex in adult humans” [Neurobiol. Stress, 25 (July 2023), 100556]","authors":"Luisa Herrmann ,&nbsp;Johanna Ade ,&nbsp;Anne Kühnel ,&nbsp;Annina Widmann ,&nbsp;Liliana Ramona Demenescu ,&nbsp;Meng Li ,&nbsp;Nils Opel ,&nbsp;Oliver Speck ,&nbsp;Martin Walter ,&nbsp;Lejla Colic","doi":"10.1016/j.ynstr.2024.100630","DOIUrl":"10.1016/j.ynstr.2024.100630","url":null,"abstract":"","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"30 ","pages":"Article 100630"},"PeriodicalIF":5.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000262/pdfft?md5=1f2c81cfe9763f17af1c9e43a53600a8&pid=1-s2.0-S2352289524000262-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140282299","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":"Chronic alcohol consumption alters sex-dependent BNST neuron function in rhesus macaques","authors":"Kristen E. Pleil ,&nbsp;Kathleen A. Grant ,&nbsp;Verginia C. Cuzon Carlson ,&nbsp;Thomas L. Kash","doi":"10.1016/j.ynstr.2024.100638","DOIUrl":"https://doi.org/10.1016/j.ynstr.2024.100638","url":null,"abstract":"<div><p>Repeated alcohol drinking contributes to a number of neuropsychiatric diseases, including alcohol use disorder and co-expressed anxiety and mood disorders. Women are more susceptible to the development and expression of these diseases with the same history of alcohol exposure as men, suggesting they may be more sensitive to alcohol-induced plasticity in limbic brain regions controlling alcohol drinking, stress responsivity, and reward processing, among other behaviors. Using a translational model of alcohol drinking in rhesus monkeys, we examined sex differences in the basal function and plasticity of neurons in the bed nucleus of the stria terminalis (BNST), a brain region in the extended amygdala shown to be a hub circuit node dysregulated in individuals with anxiety and alcohol use disorder. We performed slice electrophysiology recordings from BNST neurons in male and female monkeys following daily “open access” (22 h/day) to 4% ethanol and water for more than one year or control conditions. We found that BNST neurons from control females had reduced overall current density, hyperpolarization-activated depolarizing current (I_h), and inward rectification, as well as higher membrane resistance and greater synaptic glutamatergic release and excitatory drive, than those from control males, suggesting that female BNST neurons are more basally excited than those from males. Chronic alcohol drinking produced a shift in these measures in both sexes, decreasing current density, I_h, and inward rectification and increasing synaptic excitation. In addition, network activity-dependent synaptic inhibition was basally higher in BNST neurons of males than females, and alcohol exposure increased this in both sexes, a putative homeostatic mechanism to counter hyperexcitability. Altogether, these results suggest that the rhesus BNST is more basally excited in females than males and chronic alcohol drinking produces an overall increase in excitability and synaptic excitation. These results shed light on the mechanisms contributing to the female-biased susceptibility to neuropsychiatric diseases including co-expressed anxiety and alcohol use disorder.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"31 ","pages":"Article 100638"},"PeriodicalIF":5.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000341/pdfft?md5=3002d61a56fca84dfc948562804ad100&pid=1-s2.0-S2352289524000341-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825299","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":"Early-life stress impairs acquisition and retrieval of fear memories: sex-effects, corticosterone modulation, and partial prevention by targeting glucocorticoid receptors at adolescent age","authors":"Jeniffer Sanguino-Gómez,&nbsp;Harm J. Krugers","doi":"10.1016/j.ynstr.2024.100636","DOIUrl":"10.1016/j.ynstr.2024.100636","url":null,"abstract":"<div><p>The early postnatal period is a sensitive time window that is characterized by several neurodevelopmental processes that define neuronal architecture and function later in life. Here, we examined in young adult mice, using an auditory fear conditioning paradigm, whether stress during the early postnatal period 1) impacts fear acquisition and memory consolidation in male and female mice; 2) alters the fear responsiveness to corticosterone and 3) whether effects of early-life stress (ELS) can be prevented by treating mice with a glucocorticoid (GR) antagonist at adolescence. Male and female mice were exposed to a limited nesting and bedding model of ELS from postnatal day (PND) 2–9 and injected i.p with RU38486 (RU486) at adolescent age (PND 28–30). At two months of age, mice were trained in the fear conditioning (FC) paradigm (with and without post training administration of corticosterone - CORT) and freezing behavior during fear acquisition and contextual and auditory memory retrieval was scored. We observed that ELS impaired fear acquisition specifically in male mice and reduced both contextual and auditory memory retrieval in male and female mice. Acute post-training administration of CORT increased freezing levels during auditory memory retrieval in female mice but reduced freezing levels during the tone presentation in particular in control males. Treatment with RU486 prevented ELS-effects in acquisition in male mice and in females during auditory memory retrieval. In conclusion, this study highlights the long-lasting consequences of early-life stress on fear memory processing and further illustrates 1) the potential of a glucocorticoid antagonist intervention during adolescence to mitigate these effects and 2) the partial modulation of the auditory retrieval upon post training administration of CORT, with all these effects being sex-dependent.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"31 ","pages":"Article 100636"},"PeriodicalIF":5.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000328/pdfft?md5=f92e1654948ececd6ab47546667dad95&pid=1-s2.0-S2352289524000328-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140796720","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":"Physiological and behavioral contagion/buffering effects of chronic unpredictable stress in a socially enriched environment: A preliminary study","authors":"Evren Eraslan ,&nbsp;Magda J. Castelhano-Carlos ,&nbsp;Liliana Amorim ,&nbsp;Carina Soares-Cunha ,&nbsp;Ana J. Rodrigues ,&nbsp;Nuno Sousa","doi":"10.1016/j.ynstr.2024.100635","DOIUrl":"https://doi.org/10.1016/j.ynstr.2024.100635","url":null,"abstract":"<div><p>Rodents are sensitive to the emotional state of conspecifics. While the presence of affiliative social partners mitigates the physiological response to stressors (buffering), the partners of stressed individuals show behavioral and endocrine changes indicating that stress parameters can be transmitted across the group members (contagion). In this study, we investigated the social contagion/buffering phenomena in behavior and neuroendocrine mechanisms after exposure to chronic stress, in groups of rats living in the PhenoWorld (PhW). Three groups were tested (8 stressed rats, 8 unstressed rats, and a mixed group with 4 and 4) and these were analyzed under 4 conditions: stressed (pure stress group, n = 8), unstressed (naive control group, n = 8), stressed from mixed group (stressed companion group, n = 8), unstressed from mixed group (unstressed companion group, n = 8. While naive control animals remained undisturbed, pure stress group animals were all exposed to stress. Half of the animals under the mixed-treatment condition were exposed to stress (stressed companion group) and cohabitated with their unstressed partners (unstressed companion group). We confirmed the well-established chronic unpredictable stress (CUS) effects in physiological, behavioral, and neuroendocrine endpoints; body weight gain, open arm entries and time in EPM, and oxytocin receptor expression levels in the amygdala decreased by stress exposure, whereas adrenal weight was increased by stress. Furthermore, we found that playing, rearing and solitary resting behaviors decreased, whereas huddling behavior increased by CUS. In addition, we detected significant increases (stress-buffering) in body weight gain and huddling behaviors between pure stress and stress companion animals, and significant stress contagion effects in emotional behavior and oxytocin receptor expression levels between naive control and control companion groups. Hence, we demonstrate buffering and contagion effects were evident in physiological parameters, emotional behaviors, and social home-cage behaviors of rats and we suggest a possible mediation of these effects by oxytocin neurotransmission. In conclusion, the results herein suggest that the stress status of animals living in the same housing environment influences the behavior of the group.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"30 ","pages":"Article 100635"},"PeriodicalIF":5.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000316/pdfft?md5=c1574a9d6818b8f7b71d26bf1f8cca6d&pid=1-s2.0-S2352289524000316-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140551609","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":"Acute stress differentially alters reward-related decision making and inhibitory control under threat of punishment","authors":"Giulio Laino Chiavegatti,&nbsp;Stan B. Floresco","doi":"10.1016/j.ynstr.2024.100633","DOIUrl":"https://doi.org/10.1016/j.ynstr.2024.100633","url":null,"abstract":"<div><p>Acute stress has various effects on cognition, executive function and certain forms of cost/benefit decision making. Recent studies in rodents indicate that acute stress differentially alters reward-related decisions involving particular types of costs and slows choice latencies. Yet, how stress alters decisions where rewards are linked to punishment is less clear. We examined how 1 h restraint stress, followed by behavioral testing 10 min later altered action-selection on two tasks involving reward-seeking under threat of punishment in well-trained male and female rats. One study used a risky decision-making task involving choice between a small/safe reward and a large/risky one that could coincide with shock, delivered with a probability that increased over blocks of trials. Stress increased risk aversion and punishment sensitivity, reducing preference for the larger/risky reward, while increasing decision latencies and trial omissions in both sexes, when rats were teste. A second study used a “behavioral control” task, requiring inhibition of approach towards a readily available reward associated with punishment. Here, food pellets were delivered over discrete trials, half of which coincided with a 12 s audiovisual cue, signalling that reward retrieval prior to cue termination would deliver shock. Stress exerted sex- and timing-dependent effects on inhibitory control. Males became more impulsive and received more shocks on the stress test, whereas females were unaffected on the stress test, and were actually less impulsive when tested 24 h later. None of the effects of restraint stress were recapitulated by systemic treatment with physiological doses of corticosterone. These findings suggest acute stress induces qualitatively distinct and sometimes sex-dependent effects on punished reward-seeking that are critically dependent on whether animals must either choose between different actions or withhold them to obtain rewards and avoid punishment.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"30 ","pages":"Article 100633"},"PeriodicalIF":5.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000298/pdfft?md5=347183ecbc9b0425c32d4d37aa86444f&pid=1-s2.0-S2352289524000298-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140535646","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":"Predator odor stress reactivity, alcohol drinking and the endocannabinoid system","authors":"Laura C. Ornelas ,&nbsp;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}

{"title":"Effects of autotaxin and lysophosphatidic acid deficiencies on depression-like behaviors in mice exposed to chronic unpredictable mild stress","authors":"Chao Wang ,&nbsp;Ningyuan Li ,&nbsp;Yuqi Feng ,&nbsp;Siqi Sun ,&nbsp;Jingtong Rong ,&nbsp;Xin-hui Xie ,&nbsp;Shuxian Xu ,&nbsp;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}