Seizure activity results in increased tyrosine phosphorylation of the N-methyl-D-aspartate receptor in the hippocampus.
Systemic administration of kainic acid (KA) induces status epilepticus (SE) that causes neurodegeneration and may subsequently lead to spontaneous recurrent seizures. We investigated the effects of KA-induced SE on tyrosine phosphorylation and solubility properties of the NMDA receptor. Following 1 h of SE, total protein tyrosine phosphorylation was elevated in both the hippocampus and frontal cortex relative to controls. Tyrosine phosphorylation of the NMDA receptor subunits NR2A and NR2B was also enhanced following SE. Animals that received KA but did not develop SE, did not exhibit increased tyrosine phosphorylation. SE resulted in a decrease in the solubility of NMDA receptor subunits and of PSD-95 in 1% deoxycholate. In contrast, the detergent solubility of AMPA and kainate receptors was not affected. These findings demonstrate that SE alters tyrosine phosphorylation of the NMDA receptor, and indicate that the interaction of the NMDA receptor with other components of the NMDA receptor complex are altered as a consequence of seizure activity.
Moussa
R C
RC
Centre for the Neurobiology of Stress, Division of Life Sciences, University of Toronto at Scarborough, Canada.
Ikeda-Douglas
C J
CJ
Thakur
V
V
Milgram
N W
NW
Gurd
J W
JW
D000818:Animals; D015153:Blotting, Western; D003902:Detergents; D004591:Electrophoresis, Polyacrylamide Gel; D006624:Hippocampus / Q000378:metabolism*; D007608:Kainic Acid; D008297:Male; D010766:Phosphorylation; D011233:Precipitin Tests; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D012995:Solubility; D014443:Tyrosine / Q000378:metabolism*
D003902:Detergents; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D014443:Tyrosine; D007608:Kainic Acid