Fibroblast glutamate transport in aging and in AD: correlations with disease severity.
Altered glutamate transport and aberrant EAAT1 expression were shown in Alzheimer's disease (AD) brains. It is presently unknown whether these modifications are a consequence of neurodegeneration or play a pathogenetic role. However, recent findings of decreased glutamate uptake, EAAT1 protein and mRNA in AD platelets suggest that glutamate transporter modifications may be systemic and might explain the decreased glutamate uptake. We now used primary fibroblast cultures from 10 AD patients to further investigate the specific involvement of glutamate transporters in this disorder and in normal aging. Decreased glutamate uptake (p<0.001), EAAT1 expression (p<0.05) and mRNA (p<0.01) were observed in aged people, compared to younger controls. In AD fibroblasts, compared to age-matched controls, we observed further reductions of glutamate uptake (p<0.0005) and EAAT1 expression (p<0.005), while EAAT1 mRNA increase (p<0.001) was shown. EAAT1 parameters were mutually correlated (p<0.01) and correlations were shown with dementia severity (p<0.05 MMSE-expression, p<0.005 MMSE-mRNA). We suggest fibroblast cultures as possible ex vivo peripheral model to study the glutamate involvement and possible molecular and therapeutic targets in AD.
Zoia
Chiara P
CP
Department of Neuroscience and Biomedical Technology, University of Milano-Bicocca, Italy.
Tagliabue
Elena
E
Isella
Valeria
V
Begni
Barbara
B
Fumagalli
Lorenzo
L
Brighina
Laura
L
Appollonio
Ildebrando
I
Racchi
Marco
M
Ferrarese
Carlo
C
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D001692:Biological Transport; D002478:Cells, Cultured; D027341:Excitatory Amino Acid Transporter 1; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013223:Statistics as Topic; D027981:Symporters / Q000378:metabolism*
D027322:Amino Acid Transport System X-AG; D027341:Excitatory Amino Acid Transporter 1; D050491:Glutamate Plasma Membrane Transport Proteins; C493394:SLC1A3 protein, human; D027981:Symporters; D018698:Glutamic Acid