Selective lesions by manganese and extensive damage by iron after local injection into rat striatum or hippocampus
| Autor: | Sloot, W.N., Sluijs-Gelling, A.J. van der, Gramsbergen, J.B.P. |
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| Přispěvatelé: | Centraal Instituut voor Voedingsonderzoek TNO |
| Jazyk: | angličtina |
| Rok vydání: | 1994 |
| Předmět: |
Male
Time Factors Dopamine Calcium 45 Hippocampus Animal tissue Basal Ganglia Norepinephrine 5 Hydroxyindoleacetic acid Basal ganglion Iron overload Ferrous ion Homovanillic acid Brain injury Serotonin brain level Priority journal Manganese Poisoning Laterality Hydroxyindoleacetic Acid Brain tissue 3 o Methyldopamine 6-Hydroxydopamine inorganic chemicals Serotonin Biogenic Amines Histology Iron 3 4 Dihydroxyphenylacetic acid Neurotoxins Dose response Neurotoxicity Dopamine brain level Animal experiment Rats Wistar Support Non-U.S. Gov't Oxidopamine Manganese Analysis of Variance Dose-Response Relationship Drug Animal Neurotransmission Biogenic amine Nonhuman Corpus Striatum Rats Kinetics nervous system Autoradiography Rat 3 4-Dihydroxyphenylacetic Acid Calcium Controlled study Noradrenalin brain level |
| Zdroj: | Journal of Neurochemistry, 62, 205-216 |
| 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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