Department of Biology, Miami University, Oxford, OH 45056, USA.
Center for Bioinformatics & Functional Genomics, Miami University, Oxford, OH 45056, USA.
Neuroscience. 2024 Aug 16;553:19-39. doi: 10.1016/j.neuroscience.2024.07.002. Epub 2024 Jul 6.
Stress during adolescence clearly impacts brain development and function. Sex differences in adolescent stress-induced or exacerbated emotional and metabolic vulnerabilities could be due to sex-distinct gene expression in hypothalamic, limbic, and prefrontal brain regions. However, adolescent stress-induced whole-genome expression changes in key subregions of these brain regions were unclear. In this study, female and male adolescent Sprague Dawley rats received one-hour restraint stress daily from postnatal day (PD) 32 to PD44. Corticosterone levels, body weights, food intake, body composition, and circulating adiposity and sex hormones were measured. On PD44, brain and blood samples were collected. Using RNA-sequencing, sex-specific differences in stress-induced differentially expressed (DE) genes were identified in subregions of the hypothalamus, limbic system, and prefrontal cortex. Canonical pathways reflected well-known sex-distinct maladies and diseases, substantiating the therapeutic potential of the DE genes found in the current study. Thus, we proposed specific sex distinct, adolescent stress-induced transcriptional changes found in the current study as examples of the molecular bases for sex differences witnessed in stress induced or exacerbated emotional and metabolic disorders. Future behavioral studies and single-cell studies are warranted to test the implications of the DE genes identified in this study in sex-distinct stress-induced susceptibilities.
青春期的压力显然会影响大脑的发育和功能。青少年应激引起或加剧的情绪和代谢脆弱性的性别差异可能是由于下丘脑、边缘系统和前额叶大脑区域中性别特异的基因表达。然而，青春期应激诱导这些大脑区域关键亚区的全基因组表达变化尚不清楚。在这项研究中，雌性和雄性青春期 Sprague Dawley 大鼠从出生后第 32 天（PD）到第 44 天（PD）每天接受一小时的束缚应激。测量皮质酮水平、体重、食物摄入量、身体成分以及循环肥胖和性激素。在 PD44 时，收集大脑和血液样本。使用 RNA 测序，鉴定了下丘脑、边缘系统和前额叶皮层亚区中应激诱导的差异表达（DE）基因的性别特异性差异。经典途径反映了众所周知的性别特异疾病，证实了本研究中发现的 DE 基因的治疗潜力。因此，我们提出了目前研究中发现的特定性别差异、青少年应激诱导的转录变化，作为应激引起或加剧的情绪和代谢障碍中观察到的性别差异的分子基础的例子。未来的行为研究和单细胞研究是必要的，以检验本研究中鉴定的 DE 基因在性别特异应激易感性中的意义。
