Valentina Zonca , Moira Marizzoni , Samantha Saleri , Monica Mazzelli , Giulia Petrillo , Maria Grazia Di Benedetto , Floriana De Cillis , Marco Andrea Riva , Annamaria Cattaneo
{"title":"暴露于早期生活压力揭示了雄性和雌性成年大鼠habenula和岛叶皮层中潜在脆弱性的共同生物学特征","authors":"Valentina Zonca , Moira Marizzoni , Samantha Saleri , Monica Mazzelli , Giulia Petrillo , Maria Grazia Di Benedetto , Floriana De Cillis , Marco Andrea Riva , Annamaria Cattaneo","doi":"10.1016/j.ynstr.2025.100761","DOIUrl":null,"url":null,"abstract":"<div><div>Early-life stress (ELS) is a well-known risk factor for the development of several mental disorders later in life. The effect of ELS can be twofold: resilient individuals adapt by perceiving stress as minimal, while vulnerable ones struggle to cope with it and are predisposed to the onset of psychopathology. Although it is known that different brain regions play a role in determining ELS resilience or vulnerability, the specific mechanisms remain unclear. This preclinical study examines the effects of prenatal stress (PNS) on the functional connectivity of habenula (Hb) and insular cortex (IC) and whether these alterations predispose to stress vulnerability in adulthood. PNS was associated with reduced social interaction in both male and female animals, suggesting the onset of a potentially altered behavioural phenotype. Transcriptomic analysis of vulnerable and resilient animals revealed profound PNS-induced gene expression changes in both Hb and IC, with sex-specific patterns. In vulnerable males, pathway analysis identified a shared molecular signature between Hb and IC primarily involving the activation of inflammation and collagen-related processes. In females, vulnerability was linked to downregulation of serotonin signaling, indicating an alternative pathway to stress susceptibility compared with males. Co-expression network analysis confirmed these findings, highlighting sex-dependent biological mechanisms underlying vulnerability. These results suggest that vulnerability to stress may emerge from functional interactions between Hb and IC, mediated by distinct and sex-specific pathways.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"39 ","pages":"Article 100761"},"PeriodicalIF":3.6000,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exposure to early-life stress uncovers shared biological signatures underlying vulnerability in the habenula and insular cortex of male and female adult rats\",\"authors\":\"Valentina Zonca , Moira Marizzoni , Samantha Saleri , Monica Mazzelli , Giulia Petrillo , Maria Grazia Di Benedetto , Floriana De Cillis , Marco Andrea Riva , Annamaria Cattaneo\",\"doi\":\"10.1016/j.ynstr.2025.100761\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Early-life stress (ELS) is a well-known risk factor for the development of several mental disorders later in life. The effect of ELS can be twofold: resilient individuals adapt by perceiving stress as minimal, while vulnerable ones struggle to cope with it and are predisposed to the onset of psychopathology. Although it is known that different brain regions play a role in determining ELS resilience or vulnerability, the specific mechanisms remain unclear. This preclinical study examines the effects of prenatal stress (PNS) on the functional connectivity of habenula (Hb) and insular cortex (IC) and whether these alterations predispose to stress vulnerability in adulthood. PNS was associated with reduced social interaction in both male and female animals, suggesting the onset of a potentially altered behavioural phenotype. Transcriptomic analysis of vulnerable and resilient animals revealed profound PNS-induced gene expression changes in both Hb and IC, with sex-specific patterns. In vulnerable males, pathway analysis identified a shared molecular signature between Hb and IC primarily involving the activation of inflammation and collagen-related processes. In females, vulnerability was linked to downregulation of serotonin signaling, indicating an alternative pathway to stress susceptibility compared with males. Co-expression network analysis confirmed these findings, highlighting sex-dependent biological mechanisms underlying vulnerability. These results suggest that vulnerability to stress may emerge from functional interactions between Hb and IC, mediated by distinct and sex-specific pathways.</div></div>\",\"PeriodicalId\":19125,\"journal\":{\"name\":\"Neurobiology of Stress\",\"volume\":\"39 \",\"pages\":\"Article 100761\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurobiology of Stress\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2352289525000554\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurobiology of Stress","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2352289525000554","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Exposure to early-life stress uncovers shared biological signatures underlying vulnerability in the habenula and insular cortex of male and female adult rats
Early-life stress (ELS) is a well-known risk factor for the development of several mental disorders later in life. The effect of ELS can be twofold: resilient individuals adapt by perceiving stress as minimal, while vulnerable ones struggle to cope with it and are predisposed to the onset of psychopathology. Although it is known that different brain regions play a role in determining ELS resilience or vulnerability, the specific mechanisms remain unclear. This preclinical study examines the effects of prenatal stress (PNS) on the functional connectivity of habenula (Hb) and insular cortex (IC) and whether these alterations predispose to stress vulnerability in adulthood. PNS was associated with reduced social interaction in both male and female animals, suggesting the onset of a potentially altered behavioural phenotype. Transcriptomic analysis of vulnerable and resilient animals revealed profound PNS-induced gene expression changes in both Hb and IC, with sex-specific patterns. In vulnerable males, pathway analysis identified a shared molecular signature between Hb and IC primarily involving the activation of inflammation and collagen-related processes. In females, vulnerability was linked to downregulation of serotonin signaling, indicating an alternative pathway to stress susceptibility compared with males. Co-expression network analysis confirmed these findings, highlighting sex-dependent biological mechanisms underlying vulnerability. These results suggest that vulnerability to stress may emerge from functional interactions between Hb and IC, mediated by distinct and sex-specific pathways.
期刊介绍:
Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal.
Basic, translational and clinical research on the following topics as they relate to stress will be covered:
Molecular substrates and cell signaling,
Genetics and epigenetics,
Stress circuitry,
Structural and physiological plasticity,
Developmental Aspects,
Laboratory models of stress,
Neuroinflammation and pathology,
Memory and Cognition,
Motivational Processes,
Fear and Anxiety,
Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse),
Neuropsychopharmacology.