THE CAUSAL INVOLVEMENT OF THE BDNF-TRKB PATHWAY IN DENTATE GYRUS IN EARLY-LIFE STRESS-INDUCED COGNITIVE DEFICITS IN MALE MICE

作者：*Yaxin Sun, Yun-Ai Su, Qi Wang, Jia-Ya Zheng, Chen-Chen Zhang, Ting Wang, Xiao Liu, Yu-Nu Ma, Xue-Xin Li, Xianqiang Zhang, Xiaomeng Xie, Xiao-Dong Wang, Ji‐Tao Li, Tianmei Si · 发表于：International Journal of Neuropsychopharmacology · 年份：2025 · DOI：10.1093/ijnp/pyae059.257

Abstract Background Cognitive decline is one of the core symptoms of a variety of mental diseases. How to improve cognitive function is one of the key issues in psychiatric research.Stress, especially early-life stress, increases the prevalence of mental diseases in adult, and is often accompanied by hippocampal- related cognitive dysfunctions. However, its pathological mechanism remains unclear. Abnormal functioning of Brain-derived neurotrophic factor (BDNF) signaling pathway may be one of the mechanisms. Although the abnormal BDNF-TrkB signaling system have been found in hippocampus of the early-life stressed mice, but whether and how it mediates the cognitive dysfunction needs to be further explored. Aims & Objectives To figure out the role of hippocampus BDNF-TrkB signaling system in mediating the cognitive dysfunction caused by early-life stress, we constructed an stress model of restricted nesting materials and bedding materials in mice. Method Early stress models of restricted nesting materials and bedding were constructed from day 2 to day 9 after birth, and cognitive behavioral tests and molecular biological tests were performed in adult mice. SOR test and Y maze test were used to evaluate the spatial learning and memory ability and spatial working memory ability of mice. Immunohistochemical staining and immunofluorescence staining techniques were used to quantitatively evaluate the expression of BDNF protein in the hippocampus of mice and the number of adult neuron...