Migration of granule neurons in cerebellar organotypic cultures is impaired by methylmercury.
To examine whether abnormal migration of granule cells in the external granular layer during cerebellar development is in part of the etiology of fetal Minamata disease, organotypic culture of rat cerebellar slice was established. Migration of external granule cells pulse-labeled with bromodeoxyuridine (BrdU) toward the internal granular layer was inhibited by the presence of methylmercury (0-10 microM) in a dose-dependent manner. Nuclear condensation and DNA fragmentation visualized by the indirect immunofluorescence method with anti-BrdU antibody and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method indicated that a large fraction of cells in the external granular layer underwent apoptotic death in the slices treated with 10 microM methylmercury. Thus, methylmercury inhibits the migration of cerebellar granule cells in a model system for neural development. The impaired migration was a possible cause of the apoptotic death of external granule cells.
Kunimoto
M
M
Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan. kunimoto@nies.go.jp
Suzuki
T
T
D000818:Animals; D017209:Apoptosis; D001973:Bromodeoxyuridine; D002465:Cell Movement / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004253:DNA Nucleotidylexotransferase; D003856:Deoxyuracil Nucleotides; D017403:In Situ Hybridization; D008767:Methylmercury Compounds / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar
D003856:Deoxyuracil Nucleotides; D008767:Methylmercury Compounds; D004253:DNA Nucleotidylexotransferase; D001973:Bromodeoxyuridine