Ruojing Guo , Ye Li , Xiao Chen , Haiyan Lou , Meijian Wang , Shuyan Yu
{"title":"抑制miR-146a-5p/SMAD4信号通路可改善慢性应激引起的海马神经元损伤。","authors":"Ruojing Guo , Ye Li , Xiao Chen , Haiyan Lou , Meijian Wang , Shuyan Yu","doi":"10.1016/j.bbr.2025.115825","DOIUrl":null,"url":null,"abstract":"<div><div>Chronic stress-induced depression is a prevalent neuropsychiatric disease with high recurrence and suicide rate, which brings a heavy burden to society. However, the cure rate for depression remains comparatively low in clinical practice, partially due to the unclear pathogenesis. The present study showed that increased expression of miR-146a-5p within hippocampus may lead to depression-like behaviors in rats, accompanied by loss of neuronal dendritic spines, decreased expression of synaptic-related proteins, enhanced neuroinflammatory response and suppressed neurogenesis, effects which appear to be mediated by the SMAD4 signaling pathway. However, knock-down of miR-146a-5p within the hippocampal dentate gyrus (DG) regions of depressed rats significantly increased the expression of SMAD4, as well as restored the neural deterioration, which consequently ameliorates the depression-like behaviors in rats. In summary, these results suggest that chronic unpredicted mild stress (CUMS) may cause neuronal injury and neurogenesis deficits via up-regulating miR-146a-5p/SMAD4 pathway within the hippocampus, which provides the potential therapeutic target for the treatment of depression.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"496 ","pages":"Article 115825"},"PeriodicalIF":2.3000,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Suppression of miR-146a-5p/SMAD4 signaling pathway ameliorates hippocampal neuronal injury caused by chronic stress\",\"authors\":\"Ruojing Guo , Ye Li , Xiao Chen , Haiyan Lou , Meijian Wang , Shuyan Yu\",\"doi\":\"10.1016/j.bbr.2025.115825\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Chronic stress-induced depression is a prevalent neuropsychiatric disease with high recurrence and suicide rate, which brings a heavy burden to society. However, the cure rate for depression remains comparatively low in clinical practice, partially due to the unclear pathogenesis. The present study showed that increased expression of miR-146a-5p within hippocampus may lead to depression-like behaviors in rats, accompanied by loss of neuronal dendritic spines, decreased expression of synaptic-related proteins, enhanced neuroinflammatory response and suppressed neurogenesis, effects which appear to be mediated by the SMAD4 signaling pathway. However, knock-down of miR-146a-5p within the hippocampal dentate gyrus (DG) regions of depressed rats significantly increased the expression of SMAD4, as well as restored the neural deterioration, which consequently ameliorates the depression-like behaviors in rats. In summary, these results suggest that chronic unpredicted mild stress (CUMS) may cause neuronal injury and neurogenesis deficits via up-regulating miR-146a-5p/SMAD4 pathway within the hippocampus, which provides the potential therapeutic target for the treatment of depression.</div></div>\",\"PeriodicalId\":8823,\"journal\":{\"name\":\"Behavioural Brain Research\",\"volume\":\"496 \",\"pages\":\"Article 115825\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-09-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Behavioural Brain Research\",\"FirstCategoryId\":\"102\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0166432825004127\",\"RegionNum\":3,\"RegionCategory\":\"心理学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BEHAVIORAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Behavioural Brain Research","FirstCategoryId":"102","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0166432825004127","RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
Suppression of miR-146a-5p/SMAD4 signaling pathway ameliorates hippocampal neuronal injury caused by chronic stress
Chronic stress-induced depression is a prevalent neuropsychiatric disease with high recurrence and suicide rate, which brings a heavy burden to society. However, the cure rate for depression remains comparatively low in clinical practice, partially due to the unclear pathogenesis. The present study showed that increased expression of miR-146a-5p within hippocampus may lead to depression-like behaviors in rats, accompanied by loss of neuronal dendritic spines, decreased expression of synaptic-related proteins, enhanced neuroinflammatory response and suppressed neurogenesis, effects which appear to be mediated by the SMAD4 signaling pathway. However, knock-down of miR-146a-5p within the hippocampal dentate gyrus (DG) regions of depressed rats significantly increased the expression of SMAD4, as well as restored the neural deterioration, which consequently ameliorates the depression-like behaviors in rats. In summary, these results suggest that chronic unpredicted mild stress (CUMS) may cause neuronal injury and neurogenesis deficits via up-regulating miR-146a-5p/SMAD4 pathway within the hippocampus, which provides the potential therapeutic target for the treatment of depression.
期刊介绍:
Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.