Acrylamide induces cell death in neural progenitor cells and impairs hippocampal neurogenesis

• DOI: 10.1016/j.toxlet.2009.12.015
• Publication Date: 2009-12-25T04:11:12Z
• Authors: Hee Ra Park; Min-Sun Kim; So Jung Kim; Mikyung Park; Kyoung Hye Kong; Hyun Soo Kim; Seung Jun Kwack; Tae Seok Kang; Seung Hee Kim; Hyung Sik Kim; Jaewon Lee
• Keywords: Male; Neurons; Acrylamide; Mice, Inbred ICR; 0303 health sciences; Cell Death; Antimetabolites; Stem Cells; Blotting, Western; Hippocampus; Cell Line; 3. Good health; Mice; Oxidative Stress; 03 medical and health sciences; Animals, Newborn; Bromodeoxyuridine; Cerebellum; Animals; Benzimidazoles; Reactive Oxygen Species; Cell Proliferation; Fluorescent Dyes

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.