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

作者：Min‐Tae Jeon, Gyeong Joon Moon, Sehwan Kim, Sehwan Kim, Minji Choi, 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, Sang Ryong Kim · 发表于：British Journal of Pharmacology · 年份：2019 · DOI：10.1111/bph.14882 · 被引用次数：20 · 研究领域：Nerve injury and regeneration、Neurogenesis and neuroplasticity mechanisms、Alzheimer's disease research and treatments

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...