Linked Life Data

16407562

Source:http://linkedlifedata.com/resource/pubmed/id/16407562

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-1-12
pubmed:abstractText
Filamentous tau inclusions in neurons and glia are neuropathological hallmarks of tauopathies. The discovery of microtubule-associated protein tau gene mutations that are pathogenic for a heterogenous group of neurodegenerative disorders, called frontotemporal dementia and parkinsonism linked to chromosome-17 (FTDP-17), directly implicate tau abnormalities in the onset/progression of disease. Although the role of tau pathology in neurons in disease pathogenesis is well accepted, the contribution of glial pathology is essentially unknown. We recently generated a transgenic (Tg) mouse model of tau pathology in astrocytes by expressing the human tau protein under the control of the glial fibrillary acidic protein (GFAP) promoter. Both wild-type and FTDP-17 mutant GFAP/tau Tg animals manifest an age-dependent accumulation of tau inclusions in astrocytes that resembles the pathology observed in human tauopathies. We further demonstrate that both strains of Tg mice manifest compromised motor function that correlates with altered expression of the glial glutamate-aspartate transporter and occurs before the development of tau pathology. Subsequently, the Tg mice manifest additional deficits in neuromuscular strength that correlates with reduced expression of glutamate transporter-1 (GLT-1) and occurs concurrent with tau inclusion pathology. Reduced GLT-1 expression was associated with a progressive decrease in sodium-dependent glutamate transport capacity. Reductions in GLT-1 expression were also observed in corticobasal degeneration, a tauopathy with prominent pathology in astrocytes. Less robust changes were observed in Alzheimer's disease in which neuronal tau pathology predominates. Thus, these Tg mice recapitulate features of astrocytic pathology observed in tauopathies and implicate a role for altered astrocyte function in the pathogenesis of these disorders.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
644-54
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16407562-Amino Acid Substitution, pubmed-meshheading:16407562-Animals, pubmed-meshheading:16407562-Astrocytes, pubmed-meshheading:16407562-Central Nervous System, pubmed-meshheading:16407562-Disease Models, Animal, pubmed-meshheading:16407562-Excitatory Amino Acid Transporter 1, pubmed-meshheading:16407562-Excitatory Amino Acid Transporter 2, pubmed-meshheading:16407562-Gene Expression Regulation, pubmed-meshheading:16407562-Glial Fibrillary Acidic Protein, pubmed-meshheading:16407562-Mice, pubmed-meshheading:16407562-Mice, Inbred C3H, pubmed-meshheading:16407562-Mice, Inbred C57BL, pubmed-meshheading:16407562-Mice, Transgenic, pubmed-meshheading:16407562-Muscle Weakness, pubmed-meshheading:16407562-Mutation, Missense, pubmed-meshheading:16407562-Nerve Tissue Proteins, pubmed-meshheading:16407562-Point Mutation, pubmed-meshheading:16407562-Promoter Regions, Genetic, pubmed-meshheading:16407562-Recombinant Fusion Proteins, pubmed-meshheading:16407562-Tauopathies, pubmed-meshheading:16407562-tau Proteins
pubmed:year
2006
pubmed:articleTitle
Impaired glutamate transport in a mouse model of tau pathology in astrocytes.
pubmed:affiliation
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural