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Original Article

Exp Neurobiol 2020; 29(2): 164-175

Published online April 30, 2020

© The Korean Society for Brain and Neural Sciences

Induction of GDNF and GFRα-1 Following AAV1-Rheb(S16H) Administration in the Hippocampus in vivo

Dongyoung Yun1,2†, Min-Tae Jeon1,2†, Hyung-Jun Kim4†, Gyeong Joon Moon1,2, Shinrye Lee4, Chang Man Ha5, Minsang Shin3,6 and Sang Ryong Kim1,2,3*

1School of Life Sciences, 2BK21 plus KNU Creative BioResearch Group, 3Brain Science and Engineering Institute, Kyungpook National University, Daegu 41566, 4Dementia Research Group and Neurodegenerative Disease Group, 5Research Division and Brain Research Core Facilities, Korea Brain Research Institute, Daegu 41068, 6Department of Microbiology, School of Medicine, Kyungpook National University, Daegu 41944, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-53-950-7362, FAX: 82-53-943-2762
These authors contributed equally to this work.

Received: November 18, 2019; Revised: March 23, 2020; Accepted: March 24, 2020

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License
( which permits unrestricted non-commercial use, distribution, and
reproduction in any medium, provided the original work is properly cited.

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.

Graphical Abstract

Keywords: Rheb(S16H), Hippocampus, Astrocyte, GDNF, Neuroprotection