Role of aspartate in ischemic spinal cord damage.
To study the potentially different roles of the excitatory amino acids glutamate and aspartate in the development of ischemic injury of the spinal cord, we measured their release from cultured neurons and glial cells under ischemic conditions. We also examined changes in intracellular Ca2+ concentration and the damage elicited in cultured neurons by glutamate and aspartate. Hypoxic-hypoglycemic treatment (in vitro ischemia) elicited a rapid release of the excitatory amino acids from cultured spinal cord neurons and glial cells, but the release was greater from glial cells than from neurons. The ischemia-induced glutamate release from glial cells was transient; the aspartate release lasted longer, although the peak level was smaller than that of glutamate. In cultured neurons, a remarkable elevation in intracellular Ca2+ concentration was induced by glutamate but not by a lower concentration (10 microM) of aspartate, which is below the neurotoxic dose. At the higher concentration (100 microM), both excitatory amino acids induced a marked elevation in intracellular Ca2+ concentration and neuronal death. These results indicate that aspartate is less potent than glutamate in eliciting excitatory neurotransmission under normal physiological conditions. However, under pathological conditions such as ischemia, the increased release of aspartate from glial cells may add to the damage to neighboring neurons.
Ogata
T
T
Department of Orthopaedic Surgery, Ehime University, School of Medicine, Ehime, Japan.
Nakamura
Y
Y
Tsuji
K
K
Okumura
H
H
Kataoka
K
K
Shibata
T
T
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured / Q000502:physiology; D018846:Excitatory Amino Acids / Q000378:metabolism; D007511:Ischemia / Q000503:physiopathology*; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009498:Neurotoxins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000473:pathology*
D018846:Excitatory Amino Acids; D009498:Neurotoxins; D001224:Aspartic Acid; D002118:Calcium