Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 46241, Republic of Korea.
Int J Mol Sci. 2023 Feb 28;24(5):4688. doi: 10.3390/ijms24054688.
Early life stress (ELS) in developing children has been linked to physical and psychological sequelae in adulthood. In the present study, we investigated the effects of ELS on brain and behavioral development by establishing a novel ELS model that combined the maternal separation paradigm and mesh platform condition. We found that the novel ELS model caused anxiety- and depression-like behaviors and induced social deficits and memory impairment in the offspring of mice. In particular, the novel ELS model induced more enhanced depression-like behavior and memory impairment than the maternal separation model, which is the established ELS model. Furthermore, the novel ELS caused upregulation of arginine vasopressin expression and downregulation of GABAergic interneuron markers, such as parvalbumin (), vasoactive intestinal peptide, and calbindin-D (), in the brains of the mice. Finally, the offspring in the novel ELS model showed a decreased number of cortical PV-, CaBP-28k-positive cells and an increased number of cortical ionized calcium-binding adaptors-positive cells in their brains compared to mice in the established ELS model. Collectively, these results indicated that the novel ELS model induced more negative effects on brain and behavioral development than the established ELS model.
早期生活压力（ELS）在发育中的儿童与成年后的身体和心理后遗症有关。在本研究中，我们通过建立一种新的 ELS 模型，将母婴分离范式和网格平台条件相结合，研究了 ELS 对大脑和行为发育的影响。我们发现，新的 ELS 模型导致了焦虑和抑郁样行为，并诱导了小鼠后代的社交缺陷和记忆障碍。特别是，新的 ELS 模型比已建立的 ELS 模型——母婴分离模型引起了更增强的抑郁样行为和记忆障碍。此外，新的 ELS 导致了血管加压素表达的上调和 GABA 能中间神经元标志物，如 Parvalbumin（）、血管活性肠肽和钙结合蛋白-D（）的下调。最后，与已建立的 ELS 模型中的小鼠相比，新型 ELS 模型中的后代大脑中皮质 PV-、CaBP-28k 阳性细胞数量减少，皮质离子钙结合适应蛋白阳性细胞数量增加。总之，这些结果表明，新型 ELS 模型对大脑和行为发育的负面影响大于已建立的 ELS 模型。
