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Department of Chemitry

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British Journal of Pharmacology
년도 2020
학술지명 British Journal of Pharmacology
논문명 Neurotrophic interactions between neurons and astrocytes following AAV1-Rheb(S16H) transduction in the hippocampus in vivo
게재권/집 vol.177/ no.3 / 668-686
수록페이지
저자명 Min‐Tae Jeon, Gyeong Joon Moon, Sehwan Kim, Minji Cho, Yong‐Seok Oh, Dong Woon Kim, Hyung‐Jun Kim, Kea Joo Lee, Youngshik Choe, Chang Man Ha, Il‐Sung Jang, Michiko Nakamura, Catriona McLean, Won‐Suk Chung, Won‐Ho Shin, Seok‐Geun Lee, Sang Ryong Kim
Link 관련링크 https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.14882 6335회 연결
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.