Begni Veronica, Zampar Silvia, Longo Linda, Riva Marco Andrea
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan Italy.
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan Italy.
Neuroscience. 2020 Jun 15;437:11-22. doi: 10.1016/j.neuroscience.2020.04.018. Epub 2020 Apr 22.
The exposure to adverse environmental situations during sensitive periods of development may induce re-organizational effects on different systems and increase the vulnerability to develop psychiatric disorders later in life. The adolescent period has been demonstrated extremely susceptible to stressful events. However, most of the studies focused on the immediate effects of stress exposure and few of them investigated sex differences. This raised the question if these modulations might also be long-lasting and how the differential maturational events taking place during adolescence between males and females might have a role in the detrimental effects of stress. Given the importance of social play for the right maturation of behavior during adolescence, we used the preclinical model of social deprivation, based on the lack of all social contacts, for four weeks after weaning, followed by re-socialization until adulthood. We found that both male and female animals reared in isolation during adolescence developed an anhedonic phenotype at adulthood, without any impairments in the cognitive domain. At molecular level, these functional changes were associated with sex-specific impairments in the expression of neuroplastic markers as well as of hypothalamic-pituitary-adrenal axis-related genes. Lastly, we also reported anatomically-selective changes associated with the enduring effects of social isolation.
在发育的敏感时期暴露于不利的环境状况可能会对不同系统产生重组效应，并增加日后患精神疾病的易感性。青春期已被证明极易受到应激事件的影响。然而，大多数研究集中在应激暴露的即时效应上，很少有研究调查性别差异。这就提出了一个问题，即这些调节是否也可能是长期的，以及青春期男女之间发生的不同成熟事件如何可能在应激的有害影响中起作用。鉴于社交游戏对青春期行为正常成熟的重要性，我们采用了社会剥夺的临床前模型，即在断奶后四周内缺乏所有社会接触，随后重新社交直至成年。我们发现，青春期单独饲养的雄性和雌性动物在成年后都出现了快感缺失的表型，认知领域没有任何损伤。在分子水平上，这些功能变化与神经可塑性标记物以及下丘脑-垂体-肾上腺轴相关基因表达中的性别特异性损伤有关。最后，我们还报告了与社会隔离的持久影响相关的解剖学选择性变化。
