Abstract: Objective To explore the expression and localization of brain derived neurotrophic factor(BDNF) in neurons and astrocytes(AS) of transgenic mice with amyotrophic lateral sclerosis(ALS), and to further clarify the pathogenesis of ALS. Methods Immunofluorescence assay was used to detect the expression of BDNF in spinal cord neurons and astrocytes of 95, 108 and 122 days old ALS transgenic mice. The wild type(WT) mice were used as controls group. Neuron cell line NSC34 was used as a cell model to establish wild type and SOD1-G93A mutant NSC34 cell strains, the transgenic mice from the same litter were selected to culture the primary astrocytes. The protein expression of BDNF in NSC34 cell model and primary astrocytes was detected by Western blot. Results Compared with WT mice, the expression of BDNF in neurons was decreased in spinal cord tissues of 95, 108 and 122 days old ALS transgenic mice(P＜0.05), while the expression of BDNF/GFAP double positive cells was significantly increased.In the cell model, BDNF expression decreased in SOD1-G93A mutant NSC34 cells(P＜0.05) and increased in activated astrocytes(P＜0.05). Conclusions The expression and localization of BDNF in neurons and activated astrocytes of transgenic mice with ALS suggest that the autonomic mechanism of neurons and the non-autonomic mechanism mediated by astrocytes play an important role in the pathogenesis of ALS.

Key words: amyotrophic lateral sclerosis, brain derived neurotrophic factor, astrocyte