Title
Selective lesions by manganese and extensive damage by iron after local injection into rat striatum or hippocampus
Author
Sloot, W.N.
van der Sluijs-Gelling, A.J.
Gramsbergen, J.B.P.
Centraal Instituut voor Voedingsonderzoek TNO
Publication year
1994
Abstract
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+.
Subject
6-Hydroxydopamine
Basal ganglia
Calcium
Dopamine
Hippocampus
Iron
Manganese
Neurotoxicity
3 o Methyldopamine
3,4 Dihydroxyphenylacetic acid
5 Hydroxyindoleacetic acid
Biogenic amine
Calcium 45
Ferrous ion
Homovanillic acid
Manganese
Oxidopamine
Serotonin
Animal experiment
Animal tissue
Autoradiography
Basal ganglion
Brain injury
Brain tissue
Controlled study
Dopamine brain level
Dose response
Hippocampus
Histology
Iron overload
Male
Neurotoxicity
Neurotransmission
Nonhuman
Noradrenalin brain level
Priority journal
Rat
Serotonin brain level
3,4-Dihydroxyphenylacetic Acid
Analysis of Variance
Animal
Basal Ganglia
Biogenic Amines
Calcium
Corpus Striatum
Dopamine
Dose-Response Relationship, Drug
Hippocampus
Homovanillic Acid
Hydroxyindoleacetic Acid
Iron
Kinetics
Laterality
Male
Manganese
Manganese Poisoning
Neurotoxins
Norepinephrine
Oxidopamine
Rats
Rats, Wistar
Serotonin
Support, Non-U.S. Gov't
Time Factors
To reference this document use:
http://resolver.tudelft.nl/uuid:b396909f-39c8-4330-854b-f44861c28c13
TNO identifier
82157
Source
Journal of Neurochemistry, 62, 205-216
Bibliographical note
Correspondence Address: Sloot, W.N.; TNO Medical Biological Laboratory, Neurotoxicol./Appl. Neurosci. Dept., P.O. Box 5185, 2280 HV Rijswijk, Netherlands Chemicals/CAS: 3 o methyldopamine, 554-52-9; 3,4 dihydroxyphenylacetic acid, 102-32-9; 5 hydroxyindoleacetic acid, 1321-73-9, 54-16-0; calcium 45, 13966-05-7; ferrous ion, 15438-31-0; homovanillic acid, 306-08-1; manganese, 16397-91-4, 7439-96-5; oxidopamine, 1199-18-4, 28094-15-7, 636-00-0; serotonin, 50-67-9; 3,4-Dihydroxyphenylacetic Acid, 102-32-9; Biogenic Amines; Calcium, 7440-70-2; Dopamine, 51-61-6; Homovanillic Acid, 306-08-1; Hydroxyindoleacetic Acid, 54-16-0; Iron, 7439-89-6; Manganese, 7439-96-5; Neurotoxins; Norepinephrine, 51-41-2; Oxidopamine, 1199-18-4; Serotonin, 50-67-9
Document type
article