Differential effects of hypoxia-ischemia on subunit expression and tyrosine phosphorylation of the NMDA receptor in 7- and 21-day-old rats.
The effect of cerebral hypoxia-ischemia (HI) on levels and tyrosine phosphorylation of the NMDA receptor was examined in 7- (P7) and 21 (P21)-day-old rats. Unilateral HI was administered by ligation of the right common carotid artery and exposure to an atmosphere of 8% O2/92% N2 for 2 (P7) or 1.5 (P21) h. This duration of HI produces significant infarction in nearly all of the survivors with damage being largely restricted to the cortex, striatum, and hippocampus of the hemisphere ipsilateral to the carotid artery ligation. NR2A levels in the right hemisphere of P7 pups were markedly reduced after 24 h of recovery, while NR1 and NR2B remained unchanged. In contrast, NR2B, but not NR2A, was reduced after HI at P21. At both ages, HI resulted in a transient increase in tyrosine phosphorylation of a number of forebrain proteins that peaked between 1 and 6 h of recovery. At both P7 and P21, tyrosine phosphorylation of NR2B was enhanced 1 h after HI and had returned to basal levels by 24 h. HI induced an increase in tyrosine phosphorylation of NR2A in 21 day, but not in 7-day-old animals. The differential effects of HI on the NMDA receptor at different post-natal ages may contribute to changing sensitivity to hypoxia-ischemia.
D000367:Age Factors; D000818:Animals; D002339:Carotid Arteries / Q000502:physiology; D004195:Disease Models, Animal; D000860:Hypoxia / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D015151:Immunoblotting; D008026:Ligation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D016548:Prosencephalon / Q000737:chemistry / Q000378:metabolism*; D021122:Protein Subunits; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D014443:Tyrosine