Adult neural progenitor cells from Huntington's disease mouse brain exhibit increased proliferation and migration due to enhanced calcium and ROS signals.
OBJECTIVE
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.


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.
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
Wenjuan
W
Xie
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
Jiu-Qiang
JQ
Wang
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
Qiao-Chu
QC
Wang
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
Yun
Y
Wang
Department of Neurology, Navy General Hospital, Beijing, 100048, China.
Sheng
S
Yao
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
Tie-Shan
TS
Tang
D000818:Animals; D001921:Brain / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D018698:Glutamic Acid / Q000494:pharmacology; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
C000714328:DCX protein, human; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D017382:Reactive Oxygen Species; D018698:Glutamic Acid