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Neurotrophic interactions between neurons and astrocytes following AAV1-Rheb(S16H) transduction in the hippocampus in vivo

Title
Neurotrophic interactions between neurons and astrocytes following AAV1-Rheb(S16H) transduction in the hippocampus in vivo
Authors
Jeon, Min-TaeMoon, Gyeong JoonKim, SehwanChoi, MinjiOh, Yong-SeokKim, Dong WoonKim, Hyung-JunLee, Kea JooChoe, YoungshikHa, Chang ManJang, Il-SungNakamura, MichikoMcLean, CatrionaChung, Won-SukShin, Won-HoLee, Seok-GeunKim, Sang Ryong
DGIST Authors
Jeon, Min-Tae; Moon, Gyeong Joon; Kim, Sehwan; Choi, Minji; Oh, Yong-Seok; Kim, Dong Woon; Kim, Hyung-Jun; Lee, Kea Joo; Choe, Youngshik; Ha, Chang Man; Jang, Il-Sung; Nakamura, Michiko; McLean, Catriona; Chung, Won-Suk; Shin, Won-Ho; Lee, Seok-Geun; Kim, Sang Ryong
Issue Date
2020-02
Citation
British Journal of Pharmacology, 177(3), 668-686
Type
Article
Article Type
Article
Keywords
TYROSINE KINASE-BPARKINSONS-DISEASEDOPAMINE NEURONSMESSENGER-RNAGENE-THERAPYFULL-LENGTHMOUSE MODELBRAINEXPRESSIONRECEPTOR
ISSN
0007-1188
Abstract
Background and Purpose: We recently reported that AAV1-Rheb(S16H) transduction could protect hippocampal neurons through the induction of brain-derived neurotrophic factor (BDNF) in the rat hippocampus in vivo. It is still unclear how neuronal BDNF produced by AAV1-Rheb(S16H) transduction induces neuroprotective effects in the hippocampus and whether its up-regulation contributes to the enhance of a neuroprotective system in the adult brain. Experimental Approach: To determine the presence of a neuroprotective system in the hippocampus of patients with Alzheimer's disease (AD), we examined the levels of glial fibrillary acidic protein, BDNF and ciliary neurotrophic factor (CNTF) and their receptors, tropomyocin receptor kinase B (TrkB) and CNTF receptor α(CNTFRα), in the hippocampus of AD patients. We also determined whether AAV1-Rheb(S16H) transduction stimulates astroglial activation and whether reactive astrocytes contribute to neuroprotection in models of hippocampal neurotoxicity in vivo and in vitro. Key Results: AD patients may have a potential neuroprotective system, demonstrated by increased levels of full-length TrkB and CNTFRα in the hippocampus. Further AAV1-Rheb(S16H) transduction induced sustained increases in the levels of full-length TrkB and CNTFRα in reactive astrocytes and hippocampal neurons. Moreover, neuronal BDNF produced by Rheb(S16H) transduction of hippocampal neurons induced reactive astrocytes, resulting in CNTF production through the activation of astrocytic TrkB and the up-regulation of neuronal BDNF and astrocytic CNTF which had synergistic effects on the survival of hippocampal neurons in vivo. Conclusions and Implications: The results demonstrated that Rheb(S16H) transduction of hippocampal neurons could strengthen the neuroprotective system and this intensified system may have a therapeutic value against neurodegeneration in the adult brain. © 2019 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society
URI
http://hdl.handle.net/20.500.11750/11415
DOI
10.1111/bph.14882
Publisher
Wiley-Blackwell
Related Researcher
  • Author Oh, Yong-Seok Molecular Psychiatry Lab
  • Research Interests Monoaminergic regulation of the CNS and mood;anxiety disorder; 모노아민 (세로토닌, 도파민)에 의한 신경조절과 기분;불안 장애 기전 연구
Files:
Collection:
Department of Brain and Cognitive SciencesMolecular Psychiatry Lab1. Journal Articles


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