Decreased dendrite growth from cultured mouse cortical neurons surviving excitotoxic activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate/kainate receptors.
During cerebral ischemia, massive glutamate release leads to cell death through ionotropic glutamate receptor activation. An early consequence of this excitotoxicity is dendrite injury, which can precede cell death. We therefore tested whether cells that survived an excitotoxic insult triggered by overactivation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate (KA) subtype of ionotropic glutamate receptors displayed altered dendrite growth. We demonstrate that 24 h exposure of cultured cortical neurons to AMPA or KA dramatically reduced dendrite growth from surviving neurons. AMPA or KA exposure decreased primary dendrite number and length, and also reduced dendritic branching. The AMPA/KA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione blocked the deleterious effect of AMPA and KA on dendrite growth. These results suggest that AMPA/KA receptor overactivation may contribute to dendritic injury from neurons that survive an ischemic insult.
Monnerie
Hubert
H
Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USA.
Shashidhara
Shalini
S
Le Roux
Peter D
PD
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003712:Dendrites / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
D018683:Excitatory Amino Acid Agents; D018691:Excitatory Amino Acid Antagonists; D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins; C051774:neurofilament protein H; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid