Selective lesions by manganese and extensive damage by iron after local injection into rat striatum or hippocampus
| Jazyk: | angličtina |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Male
Time Factors Dopamine Calcium 45 Wistar Hippocampus Animal tissue Basal Ganglia Norepinephrine 5 Hydroxyindoleacetic acid Basal ganglion 4 Dihydroxyphenylacetic acid Iron overload Ferrous ion Homovanillic acid Brain injury Non-U.S. Gov't Serotonin brain level Priority journal Manganese Poisoning Laterality Hydroxyindoleacetic Acid Brain tissue Drug Support 3 o Methyldopamine 6-Hydroxydopamine inorganic chemicals Serotonin Biogenic Amines Histology Iron Neurotoxins Dose-Response Relationship 4-Dihydroxyphenylacetic Acid Dose response Neurotoxicity Dopamine brain level Animal experiment Oxidopamine Manganese Analysis of Variance Animal Neurotransmission Biogenic amine Nonhuman Corpus Striatum Rats Kinetics nervous system Autoradiography Rat Calcium Controlled study Noradrenalin brain level |
| Popis: | Regional 45Ca2+ accumulation and analysis of monoamines and metabolites in dissected tissues were used to localize, quantify, and characterize brain damage after intracerebral injections of Mn2+ into striatum and hippocampus. The specificity of Mn2+-induced lesions is described in relation to brain damage produced by local Fe2+ or 6- hydroxydopamine (6-OHDA) injections. In striatum, Fe2+ and Mn2+ produced dose-dependent (0.05-0.8 μmol) dopamine (DA) depletion, with Fe2+ being 3.4 times more potent than Mn2+. Studies examining the time course of changes in monoamine levels in striatum following local application of 0.4 μmol of Mn2+ revealed maximal depletion of all substances investigated (except 5-hydroxyindoleacetic acid) after 3 days. The effects on DA (87% depletion at day 3) and its major metabolites were most pronounced and lasted until at least 90 days (40% depletion), whereas serotonin and noradrenaline levels recovered within 21 and 42 days, respectively. In addition, levels of 3-methoxytyramine, which is used as an index of DA release, also recovered within 42 days, indicating a functional restoration of DA neurotransmission despite substantial loss of DA content. Intrastriatal Mn2+ (0.4 μmol) produced time-dependent 45Ca2+ accumulation in striatum, globus pallidus, entopeduncular nucleus, several thalamic nuclei, and substantia nigra pars reticulata ipsilateral to the injection site. In contrast, 6-OHDA injected at a dose equipotent in depleting DA produced significantly less 45Ca2+ accumulation in striatum and globus pallidus and no labeling of other brain areas, whereas Fe2+ (0.4 μmol) produced extensive 45Ca2+ accumulation throughout basal ganglia, accumbens, and cerebral cortex. In hippocampus, high Mn2+ (0.4 μmol) produced limited 45Ca2+ accumulation in subiculum and dentate gyrus, whereas low Fe2+ (0.1 μmol) produced widespread 45Ca2+ accumulation throughout hippocampus, thalamus, and cerebral cortex. It is concluded that (a) Mn2+ is selectively neurotoxic to pathways intrinsic to the basal ganglia, (b) intrastriatal injections can be used as a model for systemic Mn2+ intoxications, and (c) high endogenous Fe3+ and/or catecholamine levels potentiate the neurotoxicity of Mn2+. |
| Databáze: | OpenAIRE |
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