Glutamate and catabolites of high-energy phosphates in the striatum and brainstem of young and aged rats subchronically exposed to manganese

The degradation of high-energy phosphates was recently shown to precede man ganese-induced cellular death. We evaluated hypoxanthine, xanthine, uric ac id and glutamate levels in the striatum and brainstem of 3- and 20-month-ol d rats after subchronic oral exposure to manganese (MnCl2, 200 mg/kg/day in young rats, and 50-100 or 200 mg/kg/day in aged rats). Aged rats had highe r basal levels of hypoxanthine, xanthine, and glutamate both in the striatu m and brainstem than young rats; conversely, basal uric acid levels were lo wer in the striatum, but higher in the brainstem. Manganese induced a signi ficantly greater increase in hypoxanthine, xanthine, uric acid and glutamat e levels in aged rats than in young rats in both brain regions. These findi ngs depict a greater manganese-induced energetic impairment (increases in h ypoxanthine and xanthine levels), xanthine oxidase-induced free radical gen eration (increases in xanthine and uric acid levels), and excitotoxic statu s (increases in glutamate levels) in aged rats than in young rats. In addit ion, these findings may also account for a greater manganese toxicity to th e nigro-striatal dopaminergic system in aged than in young rats, as shown i n a previous work. (C)2000, Editrice Kurtis.