Glutamate transporters in platelets: EAAT1 decrease in aging and in Alzheimer's disease.
Platelets release glutamate upon activation and are an important clearance system of the amino acid from blood, through high-affinity glutamate uptake, similar to that described in brain synaptosomes. Since platelet glutamate uptake is decreased in neurodegenerative disorders, we performed a morphological and molecular characterization of platelet glutamate transporters. The three major brain glutamate transporters EAAT1, EAAT2 and EAAT3 are expressed in platelets, with similar molecular weight, although at lower density than brain. A Na(+)-dependent-high-affinity glutamate uptake was competitively inhibited by known inhibitors but not by dihydrokainic acid, suggesting platelet EAAT2 does not play a major role in glutamate uptake at physiological conditions. We observed decreased glutamate uptake V(max), without modification of transporter affinity, in aging, which could be linked to the selective decrease of EAAT1 expression and mRNA. Moreover, in AD patients we found a further EAAT1 reduction compared to age-matched controls, which could explain the decrease of platelet uptake previously described. Platelet glutamate transporters may be used as peripheral markers to investigate the role of glutamate in patients with neuropsychiatric disorders.
Zoia
Chiara
C
Department of Neuroscience and Biomedical Technology, University of Milano-Bicocca, 20052 (Mi), Monza, Italy.
Cogliati
Tiziana
T
Tagliabue
Elena
E
Cavaletti
Guido
G
Sala
Gessica
G
Galimberti
Gloria
G
Rivolta
Ilaria
I
Rossi
Vincenzo
V
Frattola
Lodovico
L
Ferrarese
Carlo
C
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000097:blood*; D027322:Amino Acid Transport System X-AG / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D027341:Excitatory Amino Acid Transporter 1 / Q000097:blood*; D027342:Excitatory Amino Acid Transporter 2 / Q000097:blood; D050580:Excitatory Amino Acid Transporter 3; D005260:Female; D015870:Gene Expression / Q000502:physiology; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016253:Microscopy, Immunoelectron / Q000379:methods; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D027981:Symporters / Q000097:blood
D027322:Amino Acid Transport System X-AG; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D012333:RNA, Messenger; C493400:SLC1A1 protein, human; C493397:SLC1A2 protein, human; C493394:SLC1A3 protein, human; D027981:Symporters; D018698:Glutamic Acid