Transfer of three transcription factors via a lentiviral vector ameliorates spatial learning and memory impairment in a mouse model of Alzheimer's disease.
Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder with observable memory impairment. The present study was performed to evaluate the beneficial effects of lentiviral vector-mediated overexpression of a combination of three transcription regulators, ABN (Ascl1, Brn2 and Ngn2), on learning and memory loss in a mouse model of AD. The AD model was established by injecting Aβ1-42 bilaterally into the mouse hippocampus. Lentiviral ABN was delivered bilaterally into the hippocampus of mice. Animals injected with LV-ABN showed significantly improved spatial learning and memory in the water maze test. Additionally, antibody array analysis indicated that intrahippocampal LV-ABN delivery significantly altered the expression levels of some proteins that were identified as inflammatory factors or neuroprotective and growth factors. In conclusion, our data suggest that LV-ABN delivery can ameliorate spatial learning and memory impairment in an AD mouse model, and the beneficial effect of ABN gene treatment could be linked to inhibition of the neuroinflammatory response and enhancement of neuroprotection and neurogenesis. Thus, these findings indicate that lentiviral ABN gene delivery has potential therapeutic applications for AD.
Department of neurosurgery, Subei People's Hospital of Jiangsu province, Yangzhou, China.
Pin
P
Chen
Department of neurosurgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.
Qing
Q
Yan
Department of neurosurgery, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Songtao
S
Wang
Department of neurosurgery, Subei People's Hospital of Jiangsu province, Yangzhou, China. Electronic address: wangcunzu@ujs.edu.cn.
Cunzu
C
Wang
Department of neurosurgery, Jiangsu Shengze Hospital, Suzhou, China; Department of neurosurgery, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China. Electronic address: zhaopeng@njmu.edu.cn.
Peng
P
Zhao
D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D006624:Hippocampus / Q000503:physiopathology; D016086:Lentivirus / Q000235:genetics; D008297:Male; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D065853:Spatial Learning; D014157:Transcription Factors / Q000235:genetics*
D014157:Transcription Factors
Alzheimer's disease; Gene therapy; Lentiviral ABN gene delivery; Neuroinflammatory; Neuroprotection; Transcription regulators; Water maze test