title: Acrylamide induces cell death in neural progenitor cells and impairs hippocampal neurogenesis.
abstract: Acrylamide (ACR) is a well-known neurotoxin in mammalian species that causes neuropathy characterized by ataxia and skeletal muscle weakness. Therefore, ACR-mediated axon damage in the central and peripheral nervous systems is considered to be central-peripheral axonopathy. However, the molecular mechanisms underlying ACR's toxicity to neural progenitor cells are unknown. This study investigated the adverse effects of ACR on mouse multipotent neural progenitor cells and adult hippocampal neurogenesis. ACR significantly reduced the proliferation of neural progenitor cells, and high ACR concentrations induced apoptotic and necrotic cell death. We found that elevated intracellular levels of reactive oxygen species were involved in ACR-mediated cytotoxicity. Interestingly, the administration of ACR to young mice resulted in a significant decrease in the number of newly generated cells in the dentate gyrus of the hippocampus, suggesting an impairment of adult neurogenesis. These results suggest that ACR's deleterious effects on the central nervous system are due to the death of neural progenitor cells and impaired adult neurogenesis.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Pusan National University, Geumjeong-gu, Busan, Republic of Korea.
authors.forename: Hee Ra
authors.initials: HR
authors.lastname: Park
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: So Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Mikyung
authors.initials: M
authors.lastname: Park
authors.forename: Kyoung Hye
authors.initials: KH
authors.lastname: Kong
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kwack
authors.forename: Tae Seok
authors.initials: TS
authors.lastname: Kang
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Jaewon
authors.initials: J
authors.lastname: Lee
mesh_terms: D020106:Acrylamide / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D000963:Antimetabolites; D001562:Benzimidazoles; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects; D005456:Fluorescent Dyes; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects*
chemical_list: D000963:Antimetabolites; D001562:Benzimidazoles; D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; D020106:Acrylamide; D001973:Bromodeoxyuridine; C017807:bisbenzimide ethoxide trihydrochloride