Alterations of excitatory amino acid receptors in the brain of manganese-treated mice.
An excessive activation of excitatory amino acid (EAA) receptors has been associated with oxidative stress, which is considered the primary cause of manganese (Mn) poisoning neurotoxicity. Therefore, the EAA receptor distribution was analyzed by autoradiographic methods in several brain regions during Mn intoxication. We found that chronic treatment of mice with MnCl2 during 8 wk significantly alters the L-[3H]glutamate (L-[3H]Glu) binding to total glutamate (Glu) receptors, as well as to N-methyl-D-aspartate (NMDA) and quisqualate (QA) receptor subtypes. A generalized decrease of 16-24% of the L-[3H]Glu binding to total Glu receptors was found in all cortex, hippocampus, basal ganglia (except globus pallidus), and cerebellum. Saturation studies showed a significant reduction of the maximal number of receptors (Bmax) in Mn-treated mice, whereas the affinity (Kd) was not altered. L-[3H]Glu binding to NMDA sites was mainly decreased (10-21%) in a few cortical regions, basal ganglia (except globus pallidus), and hippocampus, whereas binding to QA receptor subtype was diminished (16-30%) in cortex, hippocampus, and cerebellum. The decrease of Glu receptor binding sites during Mn poisoning could reflect a receptor downregulation more than neuronal loss, since these reductions are moderate and diffuse. Thus, this down-regulation might mean a protection mechanism against an excitotoxic process associated with Mn toxicity.
Cano
G
G
Department of Neurobiology, Inbiomed-Fundacite, Maracaibo, Venezuela.
Suárez-Roca
H
H
Bonilla
E
E
D000818:Animals; D001345:Autoradiography; D001479:Basal Ganglia / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002712:Chlorides / Q000633:toxicity; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007700:Kinetics; D008297:Male; D017895:Manganese Compounds; D020149:Manganese Poisoning; D051379:Mice; D008815:Mice, Inbred Strains; D009498:Neurotoxins; D009928:Organ Specificity; D018384:Oxidative Stress; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D002712:Chlorides; D017895:Manganese Compounds; D009498:Neurotoxins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C025340:manganese chloride