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...

Full description

Bibliographic Details
Main Authors: Law, A, Weickert, C, Webster, M, Herman, M, Kleinman, J, Harrison, P
Format: Journal article
Language:English
Published: 2003
_version_ 1797079799960698880
author Law, A
Weickert, C
Webster, M
Herman, M
Kleinman, J
Harrison, P
author_facet Law, A
Weickert, C
Webster, M
Herman, M
Kleinman, J
Harrison, P
author_sort Law, A
collection OXFORD
description 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.
first_indexed 2024-03-07T00:50:57Z
format Journal article
id oxford-uuid:8664aa2e-d55b-49df-bc64-13840923732f
institution University of Oxford
language English
last_indexed 2024-03-07T00:50:57Z
publishDate 2003
record_format dspace
spelling oxford-uuid:8664aa2e-d55b-49df-bc64-13840923732f2022-03-26T22:03:37ZExpression of NMDA receptor NR1, NR2A and NR2B subunit mRNAs during development of the human hippocampal formation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8664aa2e-d55b-49df-bc64-13840923732fEnglishSymplectic Elements at Oxford2003Law, AWeickert, CWebster, MHerman, MKleinman, JHarrison, PThe 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.
spellingShingle Law, A
Weickert, C
Webster, M
Herman, M
Kleinman, J
Harrison, P
Expression of NMDA receptor NR1, NR2A and NR2B subunit mRNAs during development of the human hippocampal formation.
title Expression of NMDA receptor NR1, NR2A and NR2B subunit mRNAs during development of the human hippocampal formation.
title_full Expression of NMDA receptor NR1, NR2A and NR2B subunit mRNAs during development of the human hippocampal formation.
title_fullStr Expression of NMDA receptor NR1, NR2A and NR2B subunit mRNAs during development of the human hippocampal formation.
title_full_unstemmed Expression of NMDA receptor NR1, NR2A and NR2B subunit mRNAs during development of the human hippocampal formation.
title_short Expression of NMDA receptor NR1, NR2A and NR2B subunit mRNAs during development of the human hippocampal formation.
title_sort expression of nmda receptor nr1 nr2a and nr2b subunit mrnas during development of the human hippocampal formation
work_keys_str_mv AT lawa expressionofnmdareceptornr1nr2aandnr2bsubunitmrnasduringdevelopmentofthehumanhippocampalformation
AT weickertc expressionofnmdareceptornr1nr2aandnr2bsubunitmrnasduringdevelopmentofthehumanhippocampalformation
AT websterm expressionofnmdareceptornr1nr2aandnr2bsubunitmrnasduringdevelopmentofthehumanhippocampalformation
AT hermanm expressionofnmdareceptornr1nr2aandnr2bsubunitmrnasduringdevelopmentofthehumanhippocampalformation
AT kleinmanj expressionofnmdareceptornr1nr2aandnr2bsubunitmrnasduringdevelopmentofthehumanhippocampalformation
AT harrisonp expressionofnmdareceptornr1nr2aandnr2bsubunitmrnasduringdevelopmentofthehumanhippocampalformation