A viral vector expressing hypoxia-inducible factor 1 alpha inhibits hippocampal neuronal apoptosis.

Abstract

Hypoxia-inducible factor 1 (HIF-1) attenuates amyloid-beta protein neurotoxicity and decreases apoptosis induced by oxidative stress or hypoxia in cortical neurons. In this study, we constructed a recombinant adeno-associated virus (rAAV) vector expressing the human HIF-1α gene (rAAV-HIF-1α), and tested the assumption that rAAV-HIF-1α represses hippocampal neuronal apoptosis induced by amyloid-beta protein. Our results confirmed that rAAV-HIF-1α significantly reduces apoptosis induced by amyloid-beta protein in primary cultured hippocampal neurons. Direct intracerebral rAAV-HIF-1α administration also induced robust and prolonged HIF-1α production in rat hippocampus. Single rAAV-HIF-1α administration resulted in decreased apoptosis of hippocampal neurons in an Alzheimer's disease rat model established by intracerebroventricular injection of aggregated amyloid-beta protein (25-35). Our in vitro and in vivo findings demonstrate that HIF-1 has potential for attenuating hippocampal neuronal apoptosis induced by amyloid-beta protein, and provides experimental support for treatment of neurodegenerative diseases using gene therapy.

• Authors: Xiqing Chai, Weina Kong, Lingyun Liu, Wenguo Yu, Zhenqing Zhang, Yimin Sun
• Journal: Neural regeneration research (Neural Regen Res) Vol. 9 Issue 11 Pg. 1145-53 (Jun 01 2014) ISSN: 1673-5374 [Print] India
• PMID: 25206774 (Publication Type: Journal Article)