MODULATION OF MONOAMINE-OXIDASE ACTIVITY IN DIFFERENT BRAIN-REGIONS AND PLATELETS FOLLOWING EXPOSURE OF RATS TO METHYLMERCURY

Monoamine oxidase (MAO; EC 1.4.3.4) is known to have an important role in the regulation of biogenic amines in the brain and peripheral tiss ues. It is also known that circulating platelets represent an excellen t model for an easy assessment of the effect of MAO-B inhibitors in ex tracerebral tissue. The present study was carried out to determine the effects of methylmercury (MeHg) on the activity of MAO in synaptosome s of different brain regions of male Sprague-Dawley rats as well as in rat blood platelets both in vitro and in vivo. MeHg pretreatment inhi bited the activity of MAO in the synaptosomes of the cortex, hypothala mus, hippocampus, striatum, cerebellum, and brain stem in a concentrat ion-dependent (0-10 mu M) manner. The threshold concentration of MeHg for such inhibition in different brain synaptosomes was found to be th e same (i.e., 1 mu M) except for in the rat striatum it was 2.5 mu M, and the IC50 value for MeHg was found to be around 2.1 mu M. Significa nt inhibition of the MAO activity was also observed in synaptosomes of the cortex, cerebellum, hypothalamus, and hippocampus as well as in p latelets of rats 24 h after treatment by gavage with a total cumulativ e dose of 35 mg/kg (5 mg/kg/day for 7 days). The decrease of such acti vity was found to be at maximum in different brain synaptosomes and pl atelets 24 h following treatment with a cumulative total dose of 75 mg /kg (7.5 mg/kg/day for 10 days); the treated animals showed signs of a taxia under these conditions. The data have further shown that methylm ercury is capable of inhibiting the MAO activity in different brain sy naptosomes to different degrees but without showing any specificity to wards any specific brain region. The present in vivo results suggest t hat the platelet MAO activity may be used as a potential biomarker of early neurotoxicity due to repeated exposure to MeHg in rats. (C) 1998 Elsevier Science Inc.