Acrylamide induces cell death in neural progenitor cells and impairs hippocampal neurogenesis.
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.
Park
Hee Ra
HR
Department of Pharmacy, College of Pharmacy, Pusan National University, Geumjeong-gu, Busan, Republic of Korea.
Kim
Min-Sun
MS
Kim
So Jung
SJ
Park
Mikyung
M
Kong
Kyoung Hye
KH
Kim
Hyun Soo
HS
Kwack
Seung Jun
SJ
Kang
Tae Seok
TS
Kim
Seung Hee
SH
Kim
Hyung Sik
HS
Lee
Jaewon
J
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*
D000963:Antimetabolites; D001562:Benzimidazoles; D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; D020106:Acrylamide; D001973:Bromodeoxyuridine; C017807:bisbenzimide ethoxide trihydrochloride