Effect of chronic and unpredictable pre-gestational stress on the brain-derived neurotrophic factor-tyrosine protein kinase B signal transduction pathway in the brain of the offspring rats

Abstract

Objective To investigate the effect of chronic and unpredictable pre-gestational stress on the serum cortisol level of the offspring, as well as the expressions of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB) in hippocampus when they were 2 month old. Methods Adult female SD rats were divided randomly into 2 groups: the control group and the chronic unpredictable stress(CUS) model group.All rats were tested in the open field test and sucrose intake test before and after CUS protocol.All offspring rats were sacrificed when 2-month old.Serum cortisol (COR) levels were determined by using a standard radioimmunoassay kit.The expressions of BDNF and TrkB in hippocampus were studied by immunoreactivity quantitative analysis. Results 1.After CUS procedure, CUS group showed decreasing activities in the open field test and decreasing sucrose consumption in sucrose intake test compared to the control group and before CUS procedure.2.The serum COR levels in the female offspring rats of CUS group(128.9±7.3) μg/L were higher than those of the control group(119.9±9.0) μg/L, as well as the male offspring of CUS group(116.5±10.9) μg/L compared with the control group(105.4±10.4) μg/L, but the body weight and brain weight between the offspring of 2 groups were not statistic significance.3.Immunoreactivity quantitative analysis showed that the gray values of BDNF in the female offspring of CUS group (36.1±8.5)decreased compared with the control group(42.4±6.9), as well as the male offspring of CUS(39.6±8.4)compared with the control group(43.7±6.4).4.The gray values of TrkB in the female offspring of CUS group (47.1±2.9)decreased than the control group(50.2±3.9), as well as the male offspring of CUS(46.5±6.7)compared with control group(50.5±5.4). Conclusion Pre-gestational stress reduced the expressions of BDNF and TrkB in hippocampus of the offspring which may relate to hypothalamic pituitary adrenal. Key words: Chronic unpredictable stress; Offspring; Cortisol; Brain-derived neurotrophic factor; Tyrosine protein kinase B