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KMID : 0892920200290020164
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Experimental Neurobiology
2020 Volume.29 No. 2 p.164 ~ p.175
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Induction of GDNF and GFRα-1 Following AAV1-Rheb(S16H) Administration in the Hippocampus in vivo
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Yun Dong-Young
Jeon Min-Tae
Kim Hyung-Jun
Moon Gyeong-Joon
Lee Shin-Rye
Ha Chang-Man
Shin Min-Sang
Kim Sang-Ryong
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Abstract
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The activation of neurotrophic signaling pathways following the upregulation of glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-β family, has a potential neuroprotective effect in the adult brain. Herein, we report that hippocampal transduction of adeno-associated virus serotype 1 (AAV1) with a constitutively active form of ras homolog enriched in brain [Rheb(S16H)], which can stimulate the production of brain-derived neurotrophic factor (BDNF) in hippocampal neurons, induces the increases in expression of GDNF and GDNF family receptor α-1 (GFRα-1), in neurons and astrocytes in the hippocampus of rat brain in vivo. Moreover, upregulation of GDNF and GFRα-1 contributes to neuroprotection against thrombin-induced neurotoxicity in the hippocampus. These results suggest that AAV1-Rheb(S16H) transduction of hippocampal neurons, resulting in neurotrophic interactions between neurons and astrocytes, may be useful for neuroprotection in the adult hippocampus.
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KEYWORD
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Rheb(S16H), Hippocampus, Astrocyte, GDNF, Neuroprotection
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