Cortical neurons containing somatostatin- or parvalbumin-like immunoreactivity are atypically vulnerable to excitotoxic injury in vitro.
We exposed murine cortical neuronal cell cultures for 24 hours to defined concentrations of N-methyl-D-aspartate (NMDA), kainate, or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and assessed the resultant neuronal degeneration quantitatively by the efflux of lactate dehydrogenase to the bathing medium. The small subpopulations of neurons that stained immunohistochemically for either somatostatin- or parvalbumin-like reactivity were atypically affected by these excitotoxins. Limited exposure to kainate or AMPA did little damage to the general neuronal population, but destroyed nearly all somatostatin- or parvalbumin-reactive cells. Conversely, these immunoreactive cells were more resistant to NMDA-induced injury than the general population. In view of reports suggesting that somatostatin- and parvalbumin-reactive cortical neurons may be preferentially damaged in Alzheimer's disease, these observations support a hypothesis that the overactivation of non-NMDA receptors could be involved in Alzheimer's disease pathogenesis.
Weiss
J H
JH
Department of Neurology, Stanford University Medical Center, CA 94305.
Koh
J
J
Baimbridge
K G
KG
Choi
D W
DW
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D005333:Fetus; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D051379:Mice; D009124:Muscle Proteins / Q000032:analysis*; D016202:N-Methylaspartate; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology*; D010320:Parvalbumins / Q000032:analysis*; D013004:Somatostatin / Q000032:analysis*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D009124:Muscle Proteins; D009498:Neurotoxins; D010080:Oxazoles; D010320:Parvalbumins; D007051:Ibotenic Acid; D001224:Aspartic Acid; D013004:Somatostatin; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007770:L-Lactate Dehydrogenase; D007608:Kainic Acid