Jia Chen1,2, Tao Zhang1, Shusheng Jiao1, Xinfu Zhou3, Jinhua Zhong3, Yanjiang Wang1, Juan Liu1, Juan Deng1, Shuiping Wang2, Zhiqiang Xu1. 1. Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, PR China. 2. Department of Neurology, PLA 123 Hospital, Bengbu, PR China. 3. School of Pharmacy and Medical Sciences, Faculty of Health Sciences, University of South Australia, Adelaide, SA, Australia.
Abstract
BACKGROUND: Alzheimer's disease (AD) is pathologically known for the amyloid-β (Aβ) deposition, neurofibrillary tangles, and neuronal loss in the brain. The precursor of brain-derived neurotrophic factor (proBDNF) before proteolysis has opposing functions to its mature form in neuronal survival and neurite growth. However, the role of proBDNF in the pathogenesis of AD remains unclear. OBJECTIVE: To investigate the effects of proBDNF on neurons in vitro, and on learning and memory impairment and brain Aβ production in a transgenic AD mouse model (APPswePS1dE9). METHODS: We here examined the effects of proBDNF on the viability (MTT assay) and neurite growth (morphologic measurement) of the primary neurons in vitro. After the intracerebroventricular injection of adeno-associated virus-proBDNF (AAV-proBDNF), we then investigated the learning and memory impairment (Morris water maze) and Aβ deposition in the brains of the AD mice. RESULTS: The results showed that proBDNF could inhibit neuronal viability and neurite growth in vitro, enhance Aβ levels, and accelerate its deposition in the brain, which was consistent with the learning and memory impairment of AD mice, likely dependent on the membrane receptor of p75NTR. CONCLUSIONS: Our findings suggest that proBDNF may exert a crucially negative effect during AD pathogenesis andprogression.
BACKGROUND:Alzheimer's disease (AD) is pathologically known for the amyloid-β (Aβ) deposition, neurofibrillary tangles, and neuronal loss in the brain. The precursor of brain-derived neurotrophic factor (proBDNF) before proteolysis has opposing functions to its mature form in neuronal survival and neurite growth. However, the role of proBDNF in the pathogenesis of AD remains unclear. OBJECTIVE: To investigate the effects of proBDNF on neurons in vitro, and on learning and memory impairment and brain Aβ production in a transgenicADmouse model (APPswePS1dE9). METHODS: We here examined the effects of proBDNF on the viability (MTT assay) and neurite growth (morphologic measurement) of the primary neurons in vitro. After the intracerebroventricular injection of adeno-associated virus-proBDNF (AAV-proBDNF), we then investigated the learning and memory impairment (Morris water maze) and Aβ deposition in the brains of the ADmice. RESULTS: The results showed that proBDNF could inhibit neuronal viability and neurite growth in vitro, enhance Aβ levels, and accelerate its deposition in the brain, which was consistent with the learning and memory impairment of ADmice, likely dependent on the membrane receptor of p75NTR. CONCLUSIONS: Our findings suggest that proBDNF may exert a crucially negative effect during AD pathogenesis andprogression.
Entities:
Keywords:
Alzheimer’s disease; amyloid-β; learning and memory; neurotoxicity; p75NTR; proBDNF
Authors: Nunzio Pomara; Davide Bruno; Chelsea Reichert Plaska; Jaime Ramos-Cejudo; Ricardo S Osorio; Anilkumar Pillai; Bruno P Imbimbo; Henrik Zetterberg; Kaj Blennow Journal: Transl Psychiatry Date: 2022-07-28 Impact factor: 7.989
Authors: Maria S Gavrish; Mark D Urazov; Tatiana A Mishchenko; Victoria D Turubanova; Ekaterina A Epifanova; Victoria G Krut'; Alexey A Babaev; Maria V Vedunova; Elena V Mitroshina Journal: Int J Mol Sci Date: 2022-08-27 Impact factor: 6.208