UDPgalactose:ceramide galactosyltransferase and 2′,3′-cyclic-nucleotide 3′-phosphodiesterase activities in rat brain after long-term exposure to methylmercury or triethyllead

Abstract

Methylmercury (MeHg) and triethyllead (Et 3Pb) are known to cause neurologic impairment in human and in several animal models. In the developing central nervous system the formation of myelin is particularly vulnerable. To obtain more information on the toxic mechanisms related to dysmyelination, the effects of MeHg and Et 3Pb on two marker enzymes of myelination was assessed in developing rats. From the 5th day of life intraperitoneal injections of MeHgCl or Et 3PbCl at doses of 0.05 to 5 mg/kg body weight were administered to the rats three times a week. They were decapitated at the 21 to 23rd (group A) or at the 28 to 31st postnatal day (group B). The animals treated with 2 mg/kg MeHg or Et 3Pb appeared normal and the rate of growth was unchanged compared with that of control rats. A decreased activity of the enzymes UDP galactose:ceramide galactosyltransferase (CGalT) and 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNP) was apparent already at doses of 0.1 mg/kg in group B rats. (MeHg, 18 and 16%, respectively; Et 3Pb, 11 and 14%) and the values decreased further with increased toxic doses. In the MeHg-treated animals the exposure time was decisive for the effect; thus in group A of MeHg-treated animals the change in enzyme activities was minimal at doses which in group B had an inhibitor effect. The activities of brain acetylcholinesterase and succinate dehydrogenase were not affected. The results emphasize a common early effect of MeHg and Et 3Pb on enzymes associated with myelination in the developing central nervous system.