Lithium inhibits apoptosis of mouse neural progenitor cells.
As undifferentiated precursor cells in the CNS, neural progenitor cells (NPCs) supply new neurons and glial cells to repair damage within the adult brain. Recently, NPCs were found to undergo apoptosis. In serum-free basic fibroblast growth factor-containing culture medium, primary culture cells from fetal mouse neuroepithelium expressed nestin, and thus might be regarded as NPCs. These NPCs demonstrated apoptosis under electron microscopy and TUNEL assay. Treatment of NPCs with lithium, a specific inhibitor of glycogen synthase kinase 3beta (GSK3beta), significantly suppressed apoptosis. Activity of pro-apoptotic protease caspase-3 was not detected in either lithium-untreated or -treated NPCs. These findings suggest that lithium may protect NPCs against apoptosis by inhibiting caspase-3-independent apoptotic pathways.
Shimomura
Atsushi
A
Department of Anatomy I, Fujita Health University School of Medicine, Aichi, Japan.
Nomura
Ryuji
R
Senda
Takao
T
D000818:Animals; D017209:Apoptosis; D006690:Bisbenzimidazole / Q000378:metabolism; D002232:Carbocyanines / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; D020287:In Situ Nick-End Labeling; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins; D064231:Nestin; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure
D002232:Carbocyanines; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; C098830:TO-PRO-3; D008094:Lithium; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D006690:Bisbenzimidazole