Wenjuan Xie1, Jiu-Qiang Wang1, Qiao-Chu Wang1, Yun Wang1, Sheng Yao2, Tie-Shan Tang1. 1. State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. 2. Department of Neurology, Navy General Hospital, Beijing, 100048, China.
Abstract
OBJECTIVES: Huntington's disease (HD) is an inherited human neurodegenerative disorder characterized by uncontrollable movement, psychiatric disturbance and cognitive decline. Impaired proliferative/differentiational potentials of adult neural progenitor cells (ANPCs) have been thought to be a pathogenic mechanism involved in it. In this study, we aimed to elucidate intrinsic properties of ANPCs subjected to neurodegenerative condition in YAC128 HD mice. MATERIALS AND METHODS: ANPCs were isolated from the SVZ regions of 4-month-old WT and YAC128 mice. Cell proliferation, migration and neuronal differentiation in vitro were compared between these two genotypes with/without Ca(2+) inhibitors or ROS scavenger treatments. Differences in ANPC proliferation and differentiation capabilities in vivo between the two genotypes were evaluated using Ki-67 and Doublecortin (DCX) immunofluorescence respectively. RESULTS: Compared to WT ANPCs, YAC128 ANPCs had significantly enhanced cell proliferation, migration and neuronal differentiation in vitro, accompanied by increased Ca(2+) and ROS signals. Raised proliferation and migration in YAC128 ANPCs were abolished by Ca(2+) signalling antagonists and ROS scavenging. However, in vivo, HD ANPCs failed to show any elevated proliferation or differentiation. CONCLUSIONS: Increased Ca(2+) signalling and higher level of ROS conferred HD ANPC enhancement of proliferation and migration potentials. However, the in vivo micro-environment did not support endogenous ANPCs to respond appropriately to neuronal loss in these YAC128 mouse brains.
OBJECTIVES:Huntington's disease (HD) is an inherited human neurodegenerative disorder characterized by uncontrollable movement, psychiatric disturbance and cognitive decline. Impaired proliferative/differentiational potentials of adult neural progenitor cells (ANPCs) have been thought to be a pathogenic mechanism involved in it. In this study, we aimed to elucidate intrinsic properties of ANPCs subjected to neurodegenerative condition in YAC128HDmice. MATERIALS AND METHODS: ANPCs were isolated from the SVZ regions of 4-month-old WT and YAC128mice. Cell proliferation, migration and neuronal differentiation in vitro were compared between these two genotypes with/without Ca(2+) inhibitors or ROS scavenger treatments. Differences in ANPC proliferation and differentiation capabilities in vivo between the two genotypes were evaluated using Ki-67 and Doublecortin (DCX) immunofluorescence respectively. RESULTS: Compared to WT ANPCs, YAC128 ANPCs had significantly enhanced cell proliferation, migration and neuronal differentiation in vitro, accompanied by increased Ca(2+) and ROS signals. Raised proliferation and migration in YAC128 ANPCs were abolished by Ca(2+) signalling antagonists and ROS scavenging. However, in vivo, HD ANPCs failed to show any elevated proliferation or differentiation. CONCLUSIONS: Increased Ca(2+) signalling and higher level of ROS conferred HD ANPC enhancement of proliferation and migration potentials. However, the in vivo micro-environment did not support endogenous ANPCs to respond appropriately to neuronal loss in these YAC128mouse brains.
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