Expression of NMDA receptor NR1, NR2A and NR2B subunit mRNAs during development of the human hippocampal formation.
The N-methyl-d-aspartate receptor plays a critical role in the formation and maintenance of synapses during brain development. In the rodent, changes in subunit expression and assembly of the heteromeric receptor complex accompany these maturational processes. However, little is known about N-methyl-d-aspartate receptor subunit expression during human brain development. We used in situ hybridization to examine the distribution and relative abundance of NR1, NR2A and NR2B subunit messenger ribonucleic acids in the hippocampal formation and adjacent cortex of 34 human subjects at five stages of life (neonate, infant, adolescent, young adult and adult). At all ages, the three messenger ribonucleic acids were expressed in all subfields, predominantly by pyramidal neurons, granule cells and polymorphic hilar cells. However, their abundance varied across ontogeny. Levels of NR1 messenger ribonucleic acid in CA4, CA3 and CA2 subfields were significantly lower in the neonate than all other age groups. In the dentate gyrus, subiculum and parahippocampal gyrus, NR2B messenger ribonucleic acid levels were higher in the neonate than in older age groups. NR2A messenger ribonucleic acid levels remained constant, leading to an age-related increase in NR2A/2B transcript ratio. We conclude that N-methyl-d-aspartate receptor subunit messenger ribonucleic acids are differentially expressed during postnatal development of the human hippocampus, with a pattern similar but not identical to that seen in the rodent. Changes in subunit composition may thus contribute to maturational differences in human hippocampal N-methyl-d-aspartate receptor function, and to their role in the pathophysiology of schizophrenia and other neurodevelopmental disorders.
Law
Amanda J
AJ
Department of Psychiatry, University of Oxford, Neurosciences Building, Warneford Hospital, Oxford OX3 7JX, UK. amanda.law@psych.ox.ac.uk
Weickert
Cynthia Shannon
CS
Webster
Maree J
MJ
Herman
Mary M
MM
Kleinman
Joel E
JE
Harrison
Paul J
PJ
D015502:Absorptiometry, Photon / Q000295:instrumentation / Q000379:methods; D000293:Adolescent; D000328:Adult; D000375:Aging; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D017403:In Situ Hybridization; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D015345:Oligonucleotide Probes / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis* / Q000235:genetics
C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate