Methylmercury-induced movement and postural disorders in developing rat: regional analysis of brain catecholamines and indoleamines.
Subcutaneous administration of methylmercury (MeHg) to rats during early postnatal development resulted in movement and postural disorders by day 22-24. Tissue concentrations of norepinephrine (NE), serotonin (5-HT), dopamine (DA) and selected metabolites were measured in the cerebral cortex, spinal cord and caudate-putamen at the onset of neurological impairment and at two subclinical stages of toxicity. In the cerebral cortex there was a significant increase in tissue concentrations of 5-HT (54-81%) and 5-hydroxyindoleacetic acid (HIAA, 133-178%) at the onset of neurological impairment. Similar increases were detected in the spinal cord for 5-HT (19-43%) and HIAA (98-123%) as well as an increase in the concentration of NE (42-51%). In the caudate-putamen there were significant increases in the concentrations of NE (98-116%), HIAA (108-124%) and DA (28-29%) with a significant decrease in the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC, 20-27%); however, tissue levels of homovanillic acid (HVA) did not change significantly. Many of these changes were detected at subclinical stages of MeHg toxicity. The ratio of HIAA/5-HT, which is frequently used as an estimate of turnover for 5-HT, was significantly increased in all 3 tissues at the onset of neurological impairment (38-94%) and at one subclinical stage (47-114%). The ratio of (DOPAC + HVA)/DA was significantly decreased in caudate-putamen at all 3 stages of toxicity (18-40%). These changes indicate altered metabolism in aromatic amine systems in the developing central nervous system during the pathogenesis of MeHg-induced movement and postural disorder.
O'Kusky
J R
JR
Department of Pathology, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada.
Boyes
B E
BE
McGeer
E G
EG
D000375:Aging; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology; D002395:Catecholamines / Q000378:metabolism*; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism*; D008767:Methylmercury Compounds / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011187:Posture; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013116:Spinal Cord / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology
D001679:Biogenic Amines; D002395:Catecholamines; D008767:Methylmercury Compounds