Relationship between the apoptosis of cerebellar granule cell and changes of caspases-3 and Bcl-2 in rats with methylmercury intoxication / 临床神经病学杂志

ABSTRACT

Objective To explore the relationship between the apoptosis of cerebellar granule cell and the changes of caspases-3 and Bcl-2 in rats with methylmercury intoxication.Methods We chronologically observed the pathological changes of cerebellum in rats given methylmercury[4 mg/(kg?d)] at day 11, 15, 18 and 19. The apoptosis of cerebellar granule cell was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) method, and the relationship between the apoptosis and the expression of caspases-3 and Bcl-2 was evaluated.Results At day 18, some sparse TUNEL positive granular cells could be observed, mainly in deep lamina adjacent to the white matter. At day 19, the apoptotic cells markedly increased, while the number of granular cells decreased with a well preservation of Purkinje cells demonstrated by calvindine immunostaining. MRF-1 and glial fibrillary acidic protein(GFAP) dyeing demonstrated severe microglia reaction and astrocytosis. From day 11, caspasese-3 mRNA expression up-regulated, increased gradually and reached peak at day 18, then decreased markedly at day 19. In contrast, Bcl-2 mRNA expression down-regulated from day 11, and decreased obviously at day 19. Zic-1 as a marker of granule cell decreased gradually after methylmercury administration and indicated degeneration of granule cells.Conclusion Cerebellar granular cell degeneration induced by methylmercury is related to apoptosis mediated by caspases-3 and Bcl-2 down regulated.