Reduced dendrite growth and altered glutamic acid decarboxylase (GAD) 65- and 67-kDa isoform protein expression from mouse cortical GABAergic neurons following excitotoxic injury in vitro.
The vulnerability of brain cells to neurologic insults varies greatly, depending on their neuronal subpopulation. However, cells surviving pathological insults such as ischemia or brain trauma may undergo structural changes, e.g., altered process growth, that could compromise brain function. In this study, we examined the effect of glutamate excitotoxicity on dendrite growth from surviving cortical GABAergic neurons in vitro. Glutamate exposure did not affect GABAergic neuron viability, however, it significantly reduced dendrite growth from GABAergic neurons. This effect was blocked by the AMPA receptor antagonists NBQX and CFM-2, and mimicked by AMPA, but not NMDA. Glutamate excitotoxicity also caused an NMDA receptor-mediated decrease in the GABA synthesizing enzyme glutamic acid decarboxylase (GAD65/67) immunoreactivity from GABAergic neurons, measured using immunocytochemical and Western blot techniques. GAD is necessary for GABA synthesis; however, reduction of GABA by 3-mercaptopropionic acid (3-MPA), which inhibits GABA synthesis, did not alter dendrite growth. These results suggest that GABAergic cortical neurons are relatively resistant to excitotoxic-induced cell death, but they can display morphological and biochemical alterations which may impair their function.
Monnerie
Hubert
H
Department of Neurosurgery, University of Pennsylvania, 330 S 9th Street, 4th Floor, Philadelphia, PA 19107, USA.
Le Roux
Peter D
PD
D015097:3-Mercaptopropionic Acid / Q000633:toxicity; D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D003712:Dendrites / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000633:toxicity*; D005968:Glutamate Decarboxylase / Q000096:biosynthesis*; D018698:Glutamic Acid / Q000633:toxicity; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D004791:Enzyme Inhibitors; D018846:Excitatory Amino Acids; D007527:Isoenzymes; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D015097:3-Mercaptopropionic Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2