Abstract

Objective To explore the role of histone H3 acetylation modification of brain derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimer's disease(AD). Methods 2 months and 8 months SAMP8 mice were used as AD model. Morris water maze was used to detect the impairment of learning and memory. Western blot was used to detect BDNF protein expression in the hippocampus, and chromatin immunoprecipitation(CHIP) was applied to study the changes of histone H3 acetylation in different BDNF promoters. Results The results of water maze test showed that the time across the target quadrant in 8 months SAMP8 mice(0.9±0.4) was significant declined compared with that of 2 months SAMP8 mice(3.7±0.9) and 8 months SAMR1 mice(3.3±0.6)(all P 0.05). Conclusion Histone H3 acetylation of BDNF exon IV and VI is reduced during the development of AD, which may be the mechanism underlying the impairment of learning and memory in AD. Key words: Alzheimer disease; Learning and memory impairment; BDNF; Histone H3 acetylation; SAMP8 mice

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