Source:http://linkedlifedata.com/resource/pubmed/id/12930822
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
44
|
| pubmed:dateCreated |
2003-10-27
|
| pubmed:abstractText |
Loss-of-function mutations in parkin are the major cause of early-onset familial Parkinson's disease. To investigate the pathogenic mechanism by which loss of parkin function causes Parkinson's disease, we generated a mouse model bearing a germline disruption in parkin. Parkin-/- mice are viable and exhibit grossly normal brain morphology. Quantitative in vivo microdialysis revealed an increase in extracellular dopamine concentration in the striatum of parkin-/- mice. Intracellular recordings of medium-sized striatal spiny neurons showed that greater currents are required to induce synaptic responses, suggesting a reduction in synaptic excitability in the absence of parkin. Furthermore, parkin-/- mice exhibit deficits in behavioral paradigms sensitive to dysfunction of the nigrostriatal pathway. The number of dopaminergic neurons in the substantia nigra of parkin-/- mice, however, is normal up to the age of 24 months, in contrast to the substantial loss of nigral neurons characteristic of Parkinson's disease. Steady-state levels of CDCrel-1, synphilin-1, and alpha-synuclein, which were identified previously as substrates of the E3 ubiquitin ligase activity of parkin, are unaltered in parkin-/- brains. Together these findings provide the first evidence for a novel role of parkin in dopamine regulation and nigrostriatal function, and a non-essential role of parkin in the survival of nigral neurons in mice.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0021-9258
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| pubmed:author |
pubmed-author:AckersonLarry CLC,
pubmed-author:BhatnagarAnushreeA,
pubmed-author:CepedaCarlosC,
pubmed-author:ChesseletMarie-FrancoiseMF,
pubmed-author:FlemingSheila MSM,
pubmed-author:GajendiranMahadevanM,
pubmed-author:GoldbergMatthew SMS,
pubmed-author:KlapsteinGloria JGJ,
pubmed-author:LamHoa AHA,
pubmed-author:LevineMichael SMS,
pubmed-author:MaidmentNigel TNT,
pubmed-author:MeloniEdward GEG,
pubmed-author:PalacinoJames JJJ,
pubmed-author:RothBryan LBL,
pubmed-author:ShenJieJ,
pubmed-author:WuNanpingN
|
| pubmed:issnType |
Print
|
| pubmed:day |
31
|
| pubmed:volume |
278
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
43628-35
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:12930822-Alleles,
pubmed-meshheading:12930822-Animals,
pubmed-meshheading:12930822-Behavior, Animal,
pubmed-meshheading:12930822-Blotting, Western,
pubmed-meshheading:12930822-Brain,
pubmed-meshheading:12930822-Chromatography, High Pressure Liquid,
pubmed-meshheading:12930822-Disease Models, Animal,
pubmed-meshheading:12930822-Dopamine,
pubmed-meshheading:12930822-Electrophysiology,
pubmed-meshheading:12930822-Germ-Line Mutation,
pubmed-meshheading:12930822-Mice,
pubmed-meshheading:12930822-Mice, Transgenic,
pubmed-meshheading:12930822-Models, Genetic,
pubmed-meshheading:12930822-Neurons,
pubmed-meshheading:12930822-Parkinson Disease,
pubmed-meshheading:12930822-Receptors, Dopamine,
pubmed-meshheading:12930822-Substantia Nigra,
pubmed-meshheading:12930822-Time Factors,
pubmed-meshheading:12930822-Ubiquitin-Protein Ligases
|
| pubmed:year |
2003
|
| pubmed:articleTitle |
Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons.
|
| pubmed:affiliation |
Center for Neurologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|