TY - JOUR
T1 - Glutamate transporters in platelets
T2 - EAAT1 decrease in aging and in Alzheimer's disease
AU - Zoia, Chiara
AU - Cogliati, Tiziana
AU - Tagliabue, Elena
AU - Cavaletti, Guido
AU - Sala, Gessica
AU - Galimberti, Gloria
AU - Rivolta, Ilaria
AU - Rossi, Vincenzo
AU - Frattola, Lodovico
AU - Ferrarese, Carlo
PY - 2004/2
Y1 - 2004/2
N2 - 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.
AB - 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.
KW - EAAT2
KW - EAAT3
KW - Excitotoxicity
KW - Glutamate uptake
KW - Human peripheral marker
KW - Molecular characterization
UR - http://www.scopus.com/inward/record.url?scp=9144232864&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=9144232864&partnerID=8YFLogxK
U2 - 10.1016/S0197-4580(03)00085-X
DO - 10.1016/S0197-4580(03)00085-X
M3 - Article
C2 - 14749132
AN - SCOPUS:9144232864
VL - 25
SP - 149
EP - 157
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 2
ER -