Blockage of p75NTR ameliorates depressive-like behaviours of mice under chronic unpredictable mild stress

Abstract

The precursor of brain derived neurotrophic factor (proBDNF) and its receptor p75NTR are upregulated in depressive patients and chronic stress-induced depressive animals, suggesting that activation of p75NTR signalling may underlie pathogenesis of depression. In the present study we hypothesize that the blockade of p75NTR may have therapeutic effect on depressive mice under chronic stress. The treatment of mice with the recombinant fusion protein of p75NTR 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 p75NTR signalling can alleviate depressive and anxiety-like behaviours of chronically stressed mice and improve the dendritic spinogenesis of neurons under stress.