Neuroendocrine and neuroimmune responses in male and female rats: evidence for functional immaturity of the neuroimmune system during early adolescence.
Neuroendocrine and neuroimmune responses in male and female rats: evidence for functional immaturity of the neuroimmune system during early adolescence.
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DOI：
10.1111/ejn.15118
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发表时间：
2022-05
期刊：
影响因子：
--
通讯作者：
Deak T
中科院分区：
文献类型：
--
作者：
Marsland P;Parrella A;Orlofsky M;Lovelock DF;Vore AS;Varlinskaya EI;Deak T
青春期是一个以行为和生理快速变化为特征的发育时期，包括对压力的脆弱性增强。最近使用青春期啮齿动物模型的研究表明，神经内分泌反应存在年龄差异，并且对药物挑战的神经免疫反应减弱。本研究旨在测试这种神经免疫不敏感是否会泛化为非药物应激挑战。雄性和雌性青少年 (P29-33) 和成年 (P70-80) Sprague Dawley 大鼠接受间歇性足部电击一小时、两小时或两小时+恢复。分析了血浆皮质酮和孕酮水平以及下丘脑室旁核（PVN）、内侧杏仁核（MeA）和腹侧海马（vHPC）中几种细胞因子的基因表达和c-Fos基因表达。本研究的结果表明，对足部电击的反应存在差异，这些差异取决于年龄、性别和感兴趣的大脑区域。成年男性和女性的 PVN 中 IL-1β 和 IL-1R2 表现出时间依赖性增加，这些变化在青春期男性中并不明显，而在青春期女性中则大幅减弱。所有感兴趣区域的 TNFα 表达均下降，成年人相对于青少年表现出更多的抑制，并且男性中的年龄差异比女性中更明显。 IL-6 表达主要在青少年和成年男性和女性的 vHPC 中受到足部电击的影响，其中女性表现出 IL-6 基因表达长期升高。总之，青春期大鼠对急性应激源暴露的中枢细胞因子反应减弱，其中大脑 IL-1 信号系统的不成熟最为明显。
Adolescence is a developmental period characterized by rapid behavioral and physiological changes, including enhanced vulnerability to stress. Recent studies using rodent models of adolescence have demonstrated age differences in neuroendocrine responses and blunted neuroimmune responding to pharmacological challenges. The present study was designed to test whether this neuroimmune insensitivity would generalize to a non-pharmacological stress challenge. Male and female adolescent (P29-33) and adult (P70-80) Sprague Dawley rats were exposed to intermittent footshock for one-, two-, or two-hours + recovery. Plasma corticosterone and progesterone levels as well as gene expression of several cytokines and c-Fos gene expression in the paraventricular nucleus of the hypothalamus (PVN), the medial amygdala (MeA), and the ventral hippocampus (vHPC) were analyzed. The results of the present study demonstrated differences in response to footshock, with these differences dependent on age, sex, and brain region of interest. Adult males and females demonstrated time-dependent increases in IL-1β and IL-1R2 in the PVN, with these changes not evident in adolescent males and substantially blunted in adolescent females. TNFα expression was decreased in all regions of interest, with adults demonstrating more suppression relative to adolescents and age differences more apparent in males than in females. IL-6 expression was affected by footshock predominantly in the vHPC of adolescent and adult males and females, with females demonstrating prolonged elevation of IL-6 gene expression. In summary, central cytokine responses to acute stressor exposure are blunted in adolescent rats, with the most pronounced immaturity evident for the brain IL-1 signaling system.
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