Induction of neuronal nitric oxide synthase by methylmercury in the cerebellum

A free radical, nitric oxide (NO), besides being a messenger molecule in th e brain, becomes a neurotoxin if overproduced. We recently reported that me thylmercury (MeNg) induces neuronal NO synthase (nNOS) in Purkinje cells. I n the present study, we examined the distribution and the mechanism of nNOS induction by MeNg, Subcutaneous administration of MeHg chloride to mice, 1 0 mg/kg/day for 9 days, increased calcium-dependent NOS activity to 60% mor e than the controls only in the cerebellum but not in other brain regions. The Western blots showed a comparable increase in nNOS protein in the cereb ellum. A N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, did not b lock, but rather enhanced, the increase in the nNOS activity. Another NMDA antagonist, 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), did not affect the nNOS activity. The Western blots of protein kinase C (PKC), which is an important cofactor regulating nNOS, did not change after the a dministration of MeNg. These results show that MeNg induces biologically ac tive nNOS selectively in the cerebellum. The induction is independent of PK C and is not reduced by the blockade of the NMDA receptor J. Neurosci. Res. 55:352-356, 1999. (C) 1999 Wiley-Liss, Inc.