Effect of brain-derived neurotrophic factor infusion on rats behavioral and hippocampal glial fibrillary acidic protein expression after chronic unpredictable mild stress

Abstract

Objective To investigate the effect of brain-derived neurotrophic factor (BDNF) infusion on the rats behavioral and hippocampal glial fibrillary acidic protein (GFAP) expression after chronic unpredictable mild stress (CUMS). Methods Thirty male SD rats were randomly divided into control+saline (Control+S), CUMS+saline (CUMS+S), CUMS+BDNF (CUMS+BDNF) groups, with 10 rats in each group. Ten kinds of chronic unpredictable mild stresses were introduced for 21 days to setup the animal model of depression. BDNF (1 μg/kg) or saline (0.009) microinjections were performed on the 23rd, 29th, 36th and 44th day during experiment.And the behavioral test (sucrose preference test and open-field test) was carried out on the 22nd and 44th day during experiment. Hippocampal GFAP expressions were measured by Western blotting and realtime-PCR analysis. Results (1) On the 22nd day (before BDNF injection), the behaviors in CUMS+S group were significantly reduced as compared with Control+S group ［F(2,28)=5.83, P<0.01; F(2,28)=18.45, P<0.01; F(2,28)=20.27, P<0.01］; but on the 44th day (after BDNF injection), the behaviors in CUMS+S group was significantly higher as compared with CUMS+S group ［F(2,28)=4.18, P<0.01;F(2,28)=13.74, P<0.01; F(2,28)=12.49, P<0.01］. (2) GFAP gene expression in CUMS+S group (0.80 ± 0.01) was significantly reduced as compared with Control+S group ［F(2,28)=2.41, P<0.01］; GFAP gene expression in CUMS+BDNF group (0.88±0.04) was significantly elevated as compared with CUMS+S group ［F(2,28)=1.62,P<0.05］. (3)GFAP mRNA level in CUMS+S group (0.88 ± 0.07) was significantly reduced as compared with Control+S group (1.15 ± 0.21) ［F(2,28)=3.68, P<0.01］; GFAP mRNA level in CUMS+BDNF group (1.03±0.14) was significantly elevated as compared with CUMS+S group ［F(2,28)=1.87, P<0.05］. Conclusion Chronic unpredictable mild stress might produce anhedonic-like behaviors in sucrose consumption and open field performances, and decreased GFAP expression in rat hippocampus. Moreover, BDNF administration might partially rescue the behaviors and hippocampal GFAP expression in a rat model of depression, providing insights into the potential pharmacological role of BDNF in the major depressive disorder and stress-related disorders. Key words: Brain-derived neurotrophic factor; Hippocampus; Stress; Glial fibrillary acidic protein