| Autor: |
Yun D; School of Life Sciences, Kyungpook National University, Daegu 41566, Korea.; BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea., Jeon MT; School of Life Sciences, Kyungpook National University, Daegu 41566, Korea.; BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea., Kim HJ; Dementia Research Group and Neurodegenerative Disease Group, Daegu 41068, Korea., Moon GJ; School of Life Sciences, Kyungpook National University, Daegu 41566, Korea.; BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea., Lee S; Dementia Research Group and Neurodegenerative Disease Group, Daegu 41068, Korea., Ha CM; Research Division and Brain Research Core Facilities, Korea Brain Research Institute, Daegu 41068, Korea., Shin M; Brain Science and Engineering Institute, Kyungpook National University, Daegu 41566, Korea.; Department of Microbiology, School of Medicine, Kyungpook National University, Daegu 41944, Korea., Kim SR; School of Life Sciences, Kyungpook National University, Daegu 41566, Korea.; BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea.; Brain Science and Engineering Institute, Kyungpook National University, Daegu 41566, Korea. |
| Abstrakt: |
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. |
