Linked Life Data

12541014

Source:http://linkedlifedata.com/resource/pubmed/id/12541014

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-1-23
pubmed:abstractText
Alzheimer's disease is associated with markedly impaired cerebral glucose metabolism as detected by reduced cortical desoxyglucose utilization, by altered activities of key glycolytic enzymes or by reduced densities of cortical glucose transporter subtypes. To determine whether formation and/or deposition of beta-amyloid plays a role in the pathology of glucose metabolism, transgenic Tg2576 mice that overexpress the Swedish mutation of the human amyloid precursor protein and demonstrate a progressive, age-related cortical and hippocampal deposition of beta-amyloid plaques, were used to study expression and activity of key enzymes of brain glycolysis (phosphofructokinase, PFK) and glyconeogenesis (fructose1,6-bisphosphatase; FbPase). Quantitative RT-PCR revealed high expression levels of both C- and M-type PFK mRNA in non-transgenic mouse cerebral cortex, whilst there was little expression of the L-type. In 24-month-old transgenic Tg2576 mouse cortex, but not in 7-, 13-, and 17-month-old mice, the copy number of PFK-C mRNA was significantly reduced in comparison to non-transgenic littermates, while the mRNA level of the other PFK isoforms and FbPase did not differ between transgenic and non-transgenic tissue samples. In situ hybridization in brain sections from aged Tg2576 mice revealed reduced PFK-C mRNA expression in beta-amyloid plaque-associated neurons and upregulation in reactive astrocytes surrounding beta-amyloid deposits. The decreased PFK-C protein level detected by Western analysis in cerebral cortical tissue from 24-month-old transgenic Tg2576 mice was accompanied by reduced enzyme activity of PFK in comparison to non-transgenic littermates. Our data demonstrate that impairment of cerebral cortical glucose metabolism occurs only due to the long-lasting high beta-amyloid burden. This results from a reduction in glycolytic activity in beta-amyloid plaque-associated neurons and a concomitant upregulation in reactive, plaque-surrounding astrocytes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0300-9564
pubmed:author
pubmed:issnType
Print
pubmed:volume
110
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
77-94
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12541014-Age Factors, pubmed-meshheading:12541014-Alzheimer Disease, pubmed-meshheading:12541014-Amyloid beta-Protein Precursor, pubmed-meshheading:12541014-Animals, pubmed-meshheading:12541014-Blotting, Western, pubmed-meshheading:12541014-Cerebral Cortex, pubmed-meshheading:12541014-Disease Models, Animal, pubmed-meshheading:12541014-Fructose-Bisphosphatase, pubmed-meshheading:12541014-Glucose, pubmed-meshheading:12541014-Immunohistochemistry, pubmed-meshheading:12541014-In Situ Hybridization, pubmed-meshheading:12541014-Mice, pubmed-meshheading:12541014-Mice, Inbred C57BL, pubmed-meshheading:12541014-Mice, Transgenic, pubmed-meshheading:12541014-Mutation, pubmed-meshheading:12541014-Phosphofructokinase-1, pubmed-meshheading:12541014-Plaque, Amyloid, pubmed-meshheading:12541014-Polymerase Chain Reaction, pubmed-meshheading:12541014-RNA, Messenger, pubmed-meshheading:12541014-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2003
pubmed:articleTitle
Cortical glucose metabolism is altered in aged transgenic Tg2576 mice that demonstrate Alzheimer plaque pathology.
pubmed:affiliation
Institute of Biochemistry, University of Leipzig, Leipzig, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't