Decreased dendrite growth from cultured mouse cortical neurons surviving excitotoxic activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate/kainate receptors

Abstract

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 α-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.