Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-3-15
pubmed:abstractText
Excitatory neurotransmitter dysfunction has been discussed to be involved in the pathophysiology of Alzheimer's disease (AD). In the current study we investigated gene and protein expression patterns of glutamatergic receptors and transporters in brains of AD patients in various stages of disease using gene chip arrays, real time PCR and immunohistochemistry. We found marked impairment in the expression of excitatory amino acid transporters (EAAT1 and EAAT 2) at both gene and protein levels in hippocampus and gyrus frontalis medialis of AD patients, already in early clinical stages of disease. The loss of EAAT immunoreactivity was particularly obvious in the vicinity of amyloid plaques. In contrast, EAAT expression was up-regulated in the cerebellum of these patients. Furthermore, a significant up-regulation of the glutamatergic kainate (GRIK4) receptor observed by gene arrays was confirmed by quantitative RT-PCR in late stages in the hippocampus of AD patients. Moreover, there were down-regulations of other glutamatergic receptors such as NMDA (GRINL1A) and AMPA (GRIA4) receptors. Our data show marked changes in the functional elements of the glutamatergic synapses such as glutamatergic receptors and transporters and indicate impaired glutamate clearing rendering neurons susceptible to excess extracellular glutamate and support further the involvement of excitotoxic mechanisms in the pathogenesis of AD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1387-2877
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
97-116
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Alterations in expression of glutamatergic transporters and receptors in sporadic Alzheimer's disease.
pubmed:affiliation
Clinical Neurochemistry and National Parkinson Foundation Centre of Excellence Research Laboratories, Clinic and Policlinic for Psychiatry and Psychotherapy, University of Würzburg, Germany. psychpol@mail.uni-wuerzburg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't