The Relationship Of BDNF Level With Depression And Its Effect On The Differentiation Of Neural Progenitor Cells

Objective:1. To construct and optimize the detection method for BDNF, compare the body fluids concentration of BDNF between normal population and depression patients, and explore the relationship between the BDNF changes and the depression occurrence, the extent of disease, the treatment response.2. To establish the depression animal model, to observe the expression of BDNF in the brain tissue of the depressed rat. To investigate the effect of BDNF on the neurogenesis and migration of neural progenitor cells in vivo, as well as its effect on the differentiation of neural stem cell in vitro.Methods and results:1. Sample collection and detection: collecting the blood and the cerebrospinal fluid(CSF) from the normal population(n=88) and the depression patients (n=42). The supermatant of the blood and the CSF was gained by centrifugating, and the concentration of BDNF was detected by improved ELISA methods. The results indicated that the concentration of BDNF in the depression patients was lower than that of normal people. Its level showed an inverse relationship with the extent of depression, and increased markedly after an effective treatment.2. The establishment of depression rat model and the change of de novo neurogenesis: We established the depression rat model by using the methods of compulsive swimming and the chronic, mild and nonpredicted stress. Animals were divided into 3 groups including the control group(normal), the stress group and the inerference group(treatment after stress). The animals were sacrificed after 1 month, the expression of BDNF and doublecortin(Dcx) was examined by immunohistochemistry. The results indicated that the BDNF expression in the hippocampus and cortex was lower than that of control. The number of Dcx positive cells in the hippocampus of stress group, which represents the immature migrating neural cell, was much lower than that in the normal. And it increased apparently after BDNF treatment.3. Culture of neural stem cells(NSCs) and the effect of BDNF on the differentiation of NSCs: NSCs were obtained from the fetal cerebrum of SD rat , cultured with standard serum-free media, and identified by immunocytochemistry. In the differentiation course induced by fetal serum, the treatment of BDNF can promote the growth of the progeny cells as well as their neurites. The number of Tuj-1 positive cells which stands for the immature neurons was much higher in the BDNF treatment group(20.1±6.4%) when comparing with the control group(7.8%±1.65%). The number of tyrosine hydroxylase(TH) positive cells which stands for dopaminergic neurons was much higher in the BDNF treatment group(3.7±0.6%) when comparing with the control group(1.4±0.3?).Conclusions:1. The concentration of BDNF in the serum and the CSF of depression patients was apparently decreased, its concentration showed an inverse relationship with the extent of disease and increased markedly after effective treatment.2. A stable depression rat model was established by using the methods of compulsive swimming and chronic stress. The BDNF expression was down-regulated in the hippocampus and cerebral cortex area in the depression animal. The number of immature migrating neural cells(Dcx positive) was apparently increased after BDNF treatment.3. By using the cultured NSCs system, our results indicated that BDNF promoted the neural differentiation as well as their growth. It also enhanced the dopaminergic neurons ratio in the differentiated cell populations. This maybe a way BDNF plays in the depression.