Linked Life Data

10971632

Source:http://linkedlifedata.com/resource/pubmed/id/10971632

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2000-10-19
pubmed:abstractText
Although several adaptive mechanisms have been identified that mask the existence of Parkinson's disease and delay the onset and aggravation of motor symptoms, the timescale and implications of this compensatory process remain an enigma. In order to examine: (i) the nature of the dopaminergic adaptive mechanisms that come into action; (ii) their sequential activation in relation to the severity of degeneration; and (iii) their efficacy with regard to the maintenance of a normal level of basal ganglia activity, we analysed the brains of mice treated daily with 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP, 4 mg/kg, i.p.) and killed at 5-day intervals from day 0 (D0) to D20. Our results demonstrate the sequential activation of two compensatory mechanisms: (i) an increase in striatal tyrosine hydroxylase (TH) protein content attested by the persistence of TH immunolabelling up to D15, contrasting with the decrease observed in both the number of nigral TH-immunoreactive neurons (-70.2%) and striatal dopamine content (-38.4%); (ii) a downregulation of DA uptake in surviving terminals at D20 (73.4% of nigral degeneration). At this point, the failure of adaptive mechanisms to maintain striatal dopaminergic homeostasis is also illustrated by an increase in the cytochrome oxidase activity of substantia nigra pars reticulata, a marker of neuronal function. It has been postulated that an increase in dopamine release per pulse could constitute an adaptive mechanism. The data we present from our MPTP mice model infirm this hypothesis. This study explores the link between the degree of nigral degeneration and the sequential activation of dopaminergic compensatory mechanisms in the nigrostriatal pathway and, in so doing, proposes a rethink of the paradigm applied to these mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2892-900
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10971632-3,4-Dihydroxyphenylacetic Acid, pubmed-meshheading:10971632-Animals, pubmed-meshheading:10971632-Carrier Proteins, pubmed-meshheading:10971632-Cell Count, pubmed-meshheading:10971632-Corpus Striatum, pubmed-meshheading:10971632-Disease Models, Animal, pubmed-meshheading:10971632-Dopamine, pubmed-meshheading:10971632-Dopamine Plasma Membrane Transport Proteins, pubmed-meshheading:10971632-Electric Stimulation, pubmed-meshheading:10971632-Electron Transport Complex IV, pubmed-meshheading:10971632-Electrophysiology, pubmed-meshheading:10971632-Homovanillic Acid, pubmed-meshheading:10971632-MPTP Poisoning, pubmed-meshheading:10971632-Male, pubmed-meshheading:10971632-Membrane Glycoproteins, pubmed-meshheading:10971632-Membrane Transport Proteins, pubmed-meshheading:10971632-Mice, pubmed-meshheading:10971632-Mice, Inbred Strains, pubmed-meshheading:10971632-Nerve Degeneration, pubmed-meshheading:10971632-Nerve Tissue Proteins, pubmed-meshheading:10971632-Neurons, pubmed-meshheading:10971632-Parkinson Disease, Secondary, pubmed-meshheading:10971632-Substantia Nigra, pubmed-meshheading:10971632-Synaptosomes, pubmed-meshheading:10971632-Tritium, pubmed-meshheading:10971632-Tyrosine 3-Monooxygenase
pubmed:year
2000
pubmed:articleTitle
Adaptive changes in the nigrostriatal pathway in response to increased 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurodegeneration in the mouse.
pubmed:affiliation
Basal Gang, Laboratoire de Neurophysiologie, CNRS UMR 5543, Université Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France. erwan.bezard@umr5543.u-bordeaux2.fr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't