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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1993-11-23
pubmed:abstractText
The behavioural, biochemical and morphological effects of a chronic administration of low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were studied in the common marmoset. Monkeys received the toxin (1 mg/kg i.p.) twice a week for four months. Group A monkeys were studied one week after the last injection of MPTP; group B monkeys were studied eight months after the last toxic injection. The monkey behaviour was observed throughout the experiment; the biochemical and morphological correlates were studied post mortem in the neostriatum and in the substantia nigra, respectively. Data collected from MPTP-treated marmosets were compared to those obtained from sham-injected control monkeys. The results can be summarized as follows. (1) In all MPTP-treated marmosets a progressive Parkinsonism occurred. In group B monkeys, a gradual behavioural recovery was observed after MPTP was discontinued. (2) Biochemical analysis of group A marmosets showed a depletion of dopamine, of 3,4-hydroxyphenylacetic acid and of homovanillic acid, and no variations in dopamine turnover in the neostriatum of MPTP-treated marmosets. In group B, biochemical analysis showed no differences between controls and MPTP-treated animals. (3) Morphological analysis showed that the density of midbrain dopaminergic neurons located in the substantia nigra was unchanged in group A monkeys, but was reduced by 6.8% in MPTP-treated monkeys of group B. The measurement of cross-sectional area showed that midbrain dopaminergic neurons were swollen in MPTP-treated monkeys of group A, with a 11.0% increase of cell size as compared to controls. In group A the nuclei were also swollen, being 304.8% larger in MPTP-treated monkeys, with a nucleus-to-cytoplasm ratio of 65.9% (as compared to 34.0% of controls). In group B monkeys cell size was increased by 18.4% in MPTP-treated marmosets, but the nuclei were of comparable size. The present data show that a chronic administration of low doses of MPTP brings about biochemical and morphological abnormalities. The first occur acutely in terminals and are reverted early after discontinuance of exposure to the toxin; the latter occur in dopaminergic perikarya, last longer than biochemical abnormalities and, at variance with them, increase in severity after MPTP is discontinued. Morphological abnormalities include early events, such as a transient swelling of nuclei or a long-lasting swelling of neurons, and late events, such as a decrease in the number of tyrosine hydroxylase-positive perikarya.(ABSTRACT TRUNCATED AT 400 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
823-32
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8105418-1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, pubmed-meshheading:8105418-3,4-Dihydroxyphenylacetic Acid, pubmed-meshheading:8105418-Animals, pubmed-meshheading:8105418-Behavior, Animal, pubmed-meshheading:8105418-Callithrix, pubmed-meshheading:8105418-Disease Models, Animal, pubmed-meshheading:8105418-Dopamine, pubmed-meshheading:8105418-Eye Movements, pubmed-meshheading:8105418-Female, pubmed-meshheading:8105418-Homovanillic Acid, pubmed-meshheading:8105418-MPTP Poisoning, pubmed-meshheading:8105418-Male, pubmed-meshheading:8105418-Motor Activity, pubmed-meshheading:8105418-Neostriatum, pubmed-meshheading:8105418-Nerve Tissue Proteins, pubmed-meshheading:8105418-Neurons, pubmed-meshheading:8105418-Parkinson Disease, Secondary, pubmed-meshheading:8105418-Severity of Illness Index, pubmed-meshheading:8105418-Single-Blind Method, pubmed-meshheading:8105418-Substantia Nigra, pubmed-meshheading:8105418-Tyrosine 3-Monooxygenase, pubmed-meshheading:8105418-Vocalization, Animal
pubmed:year
1993
pubmed:articleTitle
Chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to monkeys: behavioural, morphological and biochemical correlates.
pubmed:affiliation
Istituto di Neurologia, Università Cattolica del Sacro Cuore, Roma, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't