Methyl aspartylphenylalanine, the pons and cerebellum in mice: An evaluation of motor, morphological, biochemical, immunohistochemical and apoptotic effects.

In this study, adult mice were assigned to five groups, and administered vehicle (distilled water), or aspartame (20, 40, 80 and 160mg/kg body weight) for 28days. Behavioural tests to assess motor-balance and gait were conducted on day 28, following which animals were sacrificed. Sections of the cerebellar cortex and pons were processed, for general histology and Bielschwosky's silver staining protocol. Glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) immunoreactivity were assessed. Antioxidant status and aspartic acid/cysteine-aspartic acid protease (caspase)-3 levels were also assessed using homogenates of the cerebellum and pons. Body weight-gain decreased significantly following aspartame consumption; while no significant changes in gait and balance were observed. Histological changes suggestive of neuronal injury were observed at 80 and 160mg/kg/day; however, no obvious neuritic plaques were seen. GFAP-reactive astrocytes and NSE-reactive neurons increased at 20, 40 and 80mg/kg, but decreased at 160mg/kg. There was derangement of oxidative status and increased caspase-3 concentration with increasing doses of aspartame; although no significant difference in aspartate level was observed. The study concluded that repeated oral administration of the higher doses of aspartame was associated with morphological alterations suggestive of neuronal injury, and derangement of antioxidant status.