Ontogeny of AMPA and NMDA receptor gene expression in the developing sheep white matter and cerebral cortex.
This study examined the hypothesis that the high prevalence of white matter injury in premature infants is associated with increased expression of calcium-permeable forms of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of glutamate receptors in pre-myelinating white matter. We characterized expression of subunits of the AMPA, and for reference, the N-methyl-d-aspartate (NMDA), glutamate receptors at 0.5, 0.65, 0.85, and term gestation in the ovine fetal white matter and cerebral cortex. There was a low expression of the critical calcium-impermeable AMPA receptor GluR2 subunit in subcortical white matter both absolutely and relative to other AMPA subunits throughout gestation. In contrast, GluR2 subunit mRNA expression fell in the cerebral cortex with increasing gestation whereas protein expression increased. These findings suggest a vulnerability of subcortical white matter to AMPA receptor-mediated calcium toxicity throughout the second half of gestation. Thus, the hypothesis that AMPA receptor-mediated glutamate toxicity contributes to brain damage in premature infants needs to be revised.
Dean
Justin M
JM
Department of Physiology, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
Fraser
Mhoyra
M
Shelling
Andrew N
AN
Bennet
Laura
L
George
Sherly
S
Shaikh
Shamim
S
Scheepens
Arjan
A
Gunn
Alistair J
AJ
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism*; D004622:Embryo, Mammalian; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D008297:Male; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012756:Sheep
D012333:RNA, Messenger; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate