Kraatz Grace, Xie Henry Tian Hao, Long Hong, Walker Claire-Dominique
Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada.
Douglas Mental Health University Institute Research Center, Montreal, Quebec, Canada.
J Neuroendocrinol. 2025 Jul;37(7):e13483. doi: 10.1111/jne.13483. Epub 2024 Dec 18.
Being raised under adverse conditions during infancy and childhood represents a significant risk factor for developing later psychopathologies and dysfunctions in emotional, affective, and cognitive abilities. Depending on the type, timing, and duration of early adversity, different consequences emerge across the sexes in both human and animal models, although our understanding of the underlying interactions between sex and early life stress (ELS) is still incomplete. In this study, we used the limited bedding (LB) paradigm, a well-described model of ELS in rat pups during the first 10 days of life, and tested whether masculinization of the female brain by neonatal injections of estradiol benzoate (EB) would recapitulate the ELS-induced vulnerability phenotype of males on morphology of the basolateral amygdala (BLA) principal neurons and pre-adolescent and adult behavior. Our results show that LB-induced morphological changes in BLA neurons of weaning female rats were eliminated by EB treatment independently of early changes in estrogen receptor (ERα) expression in this region. EB treatment synergized with LB to enhance play behavior of pre-adolescent females to levels far greater than those observed in control males. In adult offspring, LB reduced time spent in the center in males and EB tended to increase social contact time compared to normal females, but only in LB conditions. Our findings indicate that neonatal masculinization of the female brain modifies specific, but not all aspects of BLA morphology and both pre-adolescent and adult behavior that are altered by ELS.
在婴儿期和童年期处于不利条件下成长是日后出现精神病理学以及情绪、情感和认知能力功能障碍的一个重要风险因素。根据早期逆境的类型、时机和持续时间，在人类和动物模型中，不同性别会出现不同的后果，尽管我们对性别与早期生活压力（ELS）之间潜在相互作用的理解仍不完整。在本研究中，我们使用了有限垫料（LB）范式，这是一种在出生后10天内对大鼠幼崽进行ELS描述详尽的模型，并测试了通过新生期注射苯甲酸雌二醇（EB）使雌性大脑雄性化是否会在基底外侧杏仁核（BLA）主神经元形态以及青春期前和成年行为方面重现ELS诱导的雄性易感性表型。我们的结果表明，LB诱导的断奶雌性大鼠BLA神经元形态变化可通过EB处理消除，而与该区域雌激素受体（ERα）表达的早期变化无关。EB处理与LB协同作用，可增强青春期前雌性大鼠的玩耍行为，使其水平远高于对照雄性大鼠。在成年后代中，与正常雌性相比，LB减少了雄性大鼠在中央区域停留的时间，EB则倾向于增加社交接触时间，但仅在LB条件下如此。我们的研究结果表明，新生期雌性大脑雄性化会改变BLA形态的特定方面，但不是所有方面，以及ELS改变的青春期前和成年行为。
