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 tissues. It is also known that circulating platelets represent an excellent model for an easy assessment of the effect of MAO-B inhibitors in extracerebral tissue. The present study was carried out to determine the effects of methylmercury (MeHg) on the activity of MAO in synaptosomes of different brain regions of male Sprague-Dawley rats as well as in rat blood platelets both in vitro and in vivo. MeHg pretreatment inhibited the activity of MAO in the synaptosomes of the cortex, hypothalamus, hippocampus, striatum, cerebellum, and brain stem in a concentration-dependent (0-10 microM) manner. The threshold concentration of MeHg for such inhibition in different brain synaptosomes was found to be the same (i.e., 1 microM) except for in the rat striatum it was 2.5 microM, and the IC50 value for MeHg was found to be around 2.1 microM. Significant inhibition of the MAO activity was also observed in synaptosomes of the cortex, cerebellum, hypothalamus, and hippocampus as well as in platelets of rats 24 h after treatment by gavage with a total cumulative dose of 35 mg/kg (5 mg/kg/day for 7 days). The decrease of such activity was found to be at maximum in different brain synaptosomes and platelets 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 ataxia under these conditions. The data have further shown that methylmercury is capable of inhibiting the MAO activity in different brain synaptosomes to different degrees but without showing any specificity towards any specific brain region. The present in vivo results suggest that the platelet MAO activity may be used as a potential biomarker of early neurotoxicity due to repeated exposure to MeHg in rats.
Chakrabarti
S K
SK
Département de médecine du travail et d'hygiène du milieu, Faculté de médecine, Université de Montréal, Quebec, Canada.
Loua
K M
KM
Bai
C
C
Durham
H
H
Panisset
J C
JC
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008767:Methylmercury Compounds / Q000494:pharmacology*; D008995:Monoamine Oxidase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology
D008767:Methylmercury Compounds; D008995:Monoamine Oxidase; C004925:methylmercuric chloride