Linked Life Data

21192928

Source:http://linkedlifedata.com/resource/pubmed/id/21192928

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-2-15
pubmed:abstractText
The pathological hallmark of Parkinson's disease (PD) is a selective and progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). In the vast majority of cases the appearance of PD is sporadic, and its etiology remains unknown. Several postmortem studies demonstrate reduced levels of brain-derived neurotrophic factor (BDNF) in the SNc of PD patients. Application of BDNF promotes the survival of DA neurons in PD animal models. Here we show that BDNF signaling via its TrkB receptor tyrosine kinase is important for survival of nigrostriatal DA neurons in aging brains. Immunohistochemistry revealed that the TrkB receptor was expressed in DA neurons located in the SNc and ventral tegmental area (VTA). However, a significant loss of DA neurons occurred at 12-24 months of age only in the SNc but not in the VTA of TrkB hypomorphic mice in which the TrkB receptor was expressed at a quarter to a third of the normal amount. The neuronal loss was accompanied by a decrease in dopaminergic axonal terminals in the striatum and by gliosis in both the SNc and striatum. Furthermore, nigrostriatal DA neurons in the TrkB mutant mice were hypersensitive to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a mitochondrial complex I inhibitor that selectively kills DA neurons. These results suggest that BDNF-to-TrkB signaling plays an important role in the long-term maintenance of the nigrostriatal system and that its deficiency may contribute to the progression of PD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1090-2430
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
228
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
118-25
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Chronic deprivation of TrkB signaling leads to selective late-onset nigrostriatal dopaminergic degeneration.
pubmed:affiliation
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20057, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural