The precursor of brain derived neurotrophic factor (proBDNF) and its receptor p75^NTR are upregulated in depressive patients and chronic stress-induced depressive animals, suggesting that activation of p75^NTR signalling may underlie pathogenesis of depression. In the present study we hypothesize that the blockade of p75^NTR may have therapeutic effect on depressive mice under chronic stress. The treatment of mice with the recombinant fusion protein of p75^NTR extracellular domain and fragment C of immunoglobulin (p75ECD-Fc) significantly reduced the immobility time in the forced swim test and tail suspension test, and increased the time spent in the central zone in the open field test in mice exposed to chronic unpredictable mild stress (CUMS). p75ECD-Fc treatment also significantly increased the length and density of neuronal dendritic spines in the dentate gyrus and amygdala. Our data indicate that blocking p75^NTR signalling can alleviate depressive and anxiety-like behaviours of chronically stressed mice and improve the dendritic spinogenesis of neurons under stress.

脑源性神经营养因子 (proBDNF) 的前体及其受体 p75 ^NTR在抑郁症患者和慢性应激诱导的抑郁症动物中上调，表明 p75 ^NTR信号的激活可能是抑郁症发病机制的基础。在本研究中，我们假设 p75 ^NTR的阻断可能对慢性应激下的抑郁小鼠有治疗作用。p75 ^NTR重组融合蛋白对小鼠的治疗细胞外结构域和免疫球蛋白 C 片段（p75ECD-Fc）显着减少了强迫游泳试验和悬尾试验中的不动时间，并增加了暴露于慢性不可预测的轻度应激的小鼠在旷场试验中中央区的时间。 CUMS）。p75ECD-Fc 处理还显着增加了齿状回和杏仁核中神经元树突棘的长度和密度。我们的数据表明，阻断 p75 ^NTR信号可以减轻长期处于压力下的小鼠的抑郁和焦虑样行为，并改善压力下神经元的树突棘发生。