文献类型：期刊文献

英文题名：BDNF gene therapy rescues neuronal function via unique and common transcriptional responses in Aβ and tau-driven Alzheimer's disease mouse models

作者：Tang, Siqi[1];Luo, Wenshu[2];Cheng, Cheng[2,3];Shen, Leshan[3];Wu, Xia[1];Xiao, Xiao[1,2,4]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[2]Belief Biomed Inc, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Sch Bioengn, Shanghai 200237, Peoples R China;[4]Shanghai Belief Biomed Inc, Bldg 1,389 Jinglian Rd, Shanghai 200237, Peoples R China

年份：2025

卷号：43

外文期刊名：BIOCHEMISTRY AND BIOPHYSICS REPORTS

收录：WOS:【ESCI(收录号:WOS:001513601400001)】；

基金：This work was supported by the National Key Research and Development Program of China (No. 2021YFC2700803) .

语种：英文

外文关键词：BDNF; Gene therapy; Alzheimer's disease; RNA-Seq analysis; rTg4510; APP/PS1

摘要：Brain-derived neurotrophic factor (BDNF) protects neurons from degeneration, making it a promising therapeutic target for Alzheimer's disease (AD). However, the genetic regulation resulting from BDNF overexpression in the brain remains to be further illustrated. Using APP/PS1 and rTg4510 mouse models, we analyzed hippocampal transcriptomes after intrahippocampal AAVT42-BDNF injection. In APP/PS1 mice with A(3 accumulation, BDNF upregulated genes involved in neuronal signaling and downregulated neurodegenerative pathways. In rTg4510 mice with p-tau pathology, upregulated genes were associated with cell differentiation and neuronal development, while downregulated genes were related to metabolism and biosynthesis. A comparison of differentially expressed genes (DEGs) between the two strains identified eight commonly upregulated genes (Cecr2, Cdhr1, Dusp6, Pam, Rasd1, Dusp4, Htr5b, Tmem117) and two downregulated genes (Abhd14a, Pmel). Notably, three genes-Npy, Crh, Tac1-were upregulated in both models, suggesting shared neuroprotective mechanisms. These findings reveal distinct and common genetic responses to BDNF in A(3 and p-tau pathogenesis, supporting its potential as a therapeutic strategy for AD.