Cognitive impairment effects of early life stress in adolescents can be predicted with early biomarkers: Impacts of sex, experience, and cytokines.
Cognitive impairment effects of early life stress in adolescents can be predicted with early biomarkers: Impacts of sex, experience, and cytokines.
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DOI：
10.1016/j.psyneuen.2016.04.016
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发表时间：
2016-09
影响因子：
3.7
通讯作者：
Brenhouse HC
中科院分区：
文献类型：
--
作者：
Grassi-Oliveira R;Honeycutt JA;Holland FH;Ganguly P;Brenhouse HC
童年的逆境以一种性别依赖的方式增加了青春期出现的精神障碍的脆弱性。母系分离(MS)啮齿动物的早期逆境影响认知和内侧前额叶皮质(MPFC)回路。暴露在早期生活逆境中的人类和动物也表现出循环中炎性细胞因子的升高，然而这些早期测量与后来的行为缺陷的预测关系尚不清楚。在这里，雄性和雌性大鼠在出生后期间暴露于MS或对照饲养(P2-21)。在不同的发育时间点采集血样，分析促炎细胞因子IL-1β和抗炎细胞因子IL-4和IL-10，然后进行Win-Shift认知测试和分析青春期mPFC小白蛋白(PVB)免疫荧光中间神经元。通过回归分析，探讨早期细胞因子与青少年行为测量的关系。我们观察了MS对循环细胞因子的性别和年龄依赖性影响。多发性硬化症还导致青少年mPFC PVB和认知缺陷的减少，这是由性别和经验依赖的早期细胞因子表达预测的。综上所述，目前的数据显示，循环中的细胞因子和PVB水平可以预测青少年的认知缺陷，因此为早期生物标志物在调节MS诱导的行为障碍中的假定作用提供了令人信服的证据。重要的是，预测性关系往往依赖于性别和多发性硬化症病史，这表明与一般人群相比，早期生活经历可能会产生个体易感性机制。
Childhood adversity increases vulnerability to psychiatric disorders that emerge in adolescence, in a sex-dependent manner. Early adversity modeled in rodents with maternal separation (MS) affects cognition and medial prefrontal cortex (mPFC) circuitry. Humans and animals exposed to early life adversity also display heightened circulating inflammatory cytokines, however the predictive relationship of these early measures with later behavioral deficits is unknown. Here, male and female rats were exposed to MS or control rearing during the postnatal period (P2–21). Blood samples were taken at distinct developmental time points for analysis of the pro-inflammatory cytokine IL-1β and the anti-inflammatory cytokines IL-4, and IL-10, followed by win-shift cognitive testing and analysis of mPFC parvalbumin (PVB) immunofluorescent interneurons in adolescence. Regression analyses were conducted to explore the relationship between early cytokines and adolescent behavioral measures. We observed sex- and age-dependent effects of MS on circulating cytokines. MS also yielded adolescent decreases in mPFC PVB and cognitive deficits, which were predicted by early cytokine expression in a sex- and experience-dependent manner. Taken together, the present data reveals that circulating cytokines and PVB levels are predictive of adolescent cognitive deficits, and therefore provide compelling evidence for a putative role of early biomarkers in mediating MS-induced behavioral dysfunction. Importantly, predictive relationships often depended on sex and on MS history, suggesting that early life experiences may yield individualistic mechanisms of vulnerability compared to the general population.