Glutamate transporters in platelets: EAAT1 decrease in aging and in Alzheimer’s disease

• Published in: Neurobiology of aging Vol. 25; no. 2; pp. 149 - 157
• Main Authors: Zoia, Chiara, Cogliati, Tiziana, Tagliabue, Elena, Cavaletti, Guido, Sala, Gessica, Galimberti, Gloria, Rivolta, Ilaria, Rossi, Vincenzo, Frattola, Lodovico, Ferrarese, Carlo
• Format: Journal Article
• Language: English
• Published: London Elsevier Inc 01.02.2004; Elsevier Science
• Subjects: Aged; Aged, 80 and over; Aging - metabolism; Alzheimer Disease - blood; Amino Acid Transport System X-AG - blood; Biological and medical sciences; Blood Platelets - metabolism; Blood Platelets - ultrastructure; Blotting, Western - methods; Brain - metabolism; Case-Control Studies; Cell Line; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; EAAT2; EAAT3; Excitatory Amino Acid Transporter 1 - blood; Excitatory Amino Acid Transporter 2 - blood; Excitatory Amino Acid Transporter 3; Excitotoxicity; Female; Gene Expression - physiology; Glutamate Plasma Membrane Transport Proteins; Glutamate uptake; Glutamic Acid - metabolism; Human peripheral marker; Humans; Immunohistochemistry - methods; Medical sciences; Microscopy, Immunoelectron - methods; Middle Aged; Molecular characterization; Monocytes - metabolism; Monocytes - ultrastructure; Neurology; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - biosynthesis; Symporters - blood; EAAT2; Molecular characterization; Glutamate uptake; Human peripheral marker; Excitotoxicity; EAAT3; Human; Nervous system diseases; Senescence; Toxicity; Alzheimer disease; GLAST glutamate/aspartate transporter; Cerebral disorder; Platelet; Central nervous system disease; Degenerative disease
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/S0197-4580(03)00085-X

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.