Cano G, Suárez-Roca H, Bonilla E
Department of Neurobiology, Inbiomed-Fundacite, Maracaibo, Venezuela.
Mol Chem Neuropathol. 1997 Jan-Feb;30(1-2):41-52. doi: 10.1007/BF02815149.
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.
兴奋性氨基酸（EAA）受体的过度激活与氧化应激相关，氧化应激被认为是锰（Mn）中毒神经毒性的主要原因。因此，采用放射自显影法分析了锰中毒期间几个脑区的EAA受体分布。我们发现，用氯化锰对小鼠进行8周的慢性治疗，会显著改变L-[3H]谷氨酸（L-[3H]Glu）与总谷氨酸（Glu）受体以及N-甲基-D-天冬氨酸（NMDA）和quisqualate（QA）受体亚型的结合。在所有皮质、海马、基底神经节（苍白球除外）和小脑中，L-[3H]Glu与总Glu受体的结合普遍减少了16%-24%。饱和研究表明，锰处理小鼠的受体最大数量（Bmax）显著减少，而亲和力（Kd）未改变。L-[3H]Glu与NMDA位点的结合在少数皮质区域、基底神经节（苍白球除外）和海马中主要减少（10%-21%），而与QA受体亚型的结合在皮质、海马和小脑中减少（16%-30%）。锰中毒期间Glu受体结合位点的减少可能反映的是受体下调而非神经元损失，因为这些减少是适度且弥散的。因此，这种下调可能意味着一种针对与锰毒性相关的兴奋性毒性过程的保护机制。
