Neurotrophic interactions between neurons and astrocytes following AAV1-Rheb(S16H) transduction in the hippocampus in vivo
| Autor: | Won-Suk Chung, Il Sung Jang, Kea Joo Lee, Catriona McLean, Yong-Seok Oh, Gyeong Joon Moon, Seok-Geun Lee, Sang Ryong Kim, Youngshik Choe, Min Tae Jeon, Won Ho Shin, Sehwan Kim, Dong Woon Kim, Hyung-Jun Kim, Michiko Nakamura, Chang Man Ha, Minji Choi |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Tropomyosin receptor kinase B Ciliary neurotrophic factor Hippocampal formation Neuroprotection Hippocampus 03 medical and health sciences 0302 clinical medicine Neurotrophic factors Glial Fibrillary Acidic Protein medicine Humans Pharmacology Neurons biology Chemistry Brain-Derived Neurotrophic Factor Neurodegeneration medicine.disease Research Papers 030104 developmental biology Neuroprotective Agents nervous system Astrocytes biology.protein Ras Homolog Enriched in Brain Protein Neuroscience 030217 neurology & neurosurgery Neurotrophin RHEB Research Paper |
| Zdroj: | British Journal of Pharmacology |
| ISSN: | 1476-5381 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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