Cited by 110Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismSchizophrenia research and treatment

Developmental regulation of the NMDA receptor subunits, NR3A and NR1, in human prefrontal cortex

Open access
Henson, Maile A., Roberts, Adam C., Salimi, Kayvon, Vadlamudi, Swarooparani, Hamer, Robert M., Gilmore, John H., Jarskog, L. Fredrik, Philpot, Benjamin D.·2008·Cerebral Cortex

Abstract

Subunit composition of N-methyl-D-aspartate-type glutamate receptors (NMDARs) dictates their function, yet the ontogenic profiles of human NMDAR subunits from gestation to adulthood have not been determined. We examined NMDAR mRNA and protein development in human dorsolateral prefrontal cortex (DLPFC), an area in which NMDARs are critical for higher cognitive processing and NMDAR hypofunction is hypothesized in schizophrenia. Using quantitative reverse transcriptase-polymerase chain reaction and western blotting, we found NR1 expression begins low prenatally, peaks in adolescence, yet remains high throughout life, suggesting lifelong importance of NMDAR function. In contrast, NR3A levels are low during gestation, surge soon after birth, and decline progressively through adolescence and into adulthood. Because NR3A subunits uniquely attenuate NMDAR-mediated currents, limit calcium influx, and suppress dendritic spine formation, high levels during early childhood may be important for regulating neuroprotection and activity-dependent sculpting of synapses. We also examined whether subunit changes underlie reduced NMDAR activity in schizophrenia. Our results reveal normal NR1 and NR3A protein levels in DLPFC from schizophrenic patients, indicating that NMDAR hypofunction is unlikely to be maintained by gross changes in NR3A-containing NMDARs or overall NMDAR numbers. These data provide insights into NMDAR functions in the developing CNS and will contribute to designing pharmacotherapies for neurological disorders.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/cercor/bhn017

Cites

132 of 132 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Henson, M. A., Roberts, A. C., Salimi, K., Vadlamudi, S., Hamer, R. M., Gilmore, J. H., Jarskog, L. F., & Philpot, B. D.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • New York State Psychiatric Institute (US)
Venue
Cerebral Cortex
Published
2008-02-21
Volume
18
Issue
11
Pages
2560-2573
ISSN
  • 1047-3211 (ISSN-L)
  • 1460-2199
OpenAlex
W2166442546
Cited by
110
References
132
Citations by year
2026: 2 · 2025: 10 · 2024: 4 · 2023: 7 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 6 · 2016: 8 · 2015: 7 · 2014: 3 · 2013: 7 · 2012: 7
FWCI
3.32
Type
journal article
Language
en
Open access
Locations
  • Cerebral Cortex (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • UNC Libraries
Funders
  • National Alliance for Research on Schizophrenia and Depression
  • University of North Carolina at Chapel Hill
  • National Institute of Mental Health (MH064065, P50MH064065)
  • National Eye Institute (R01EY018323)
  • National Institute of General Medical Sciences (R25GM055336)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
NMDA receptor, NR1 subunit, ontogeny, schizophrenia, NMDA receptor hypofunction, dendritic spine formation, calcium influx, neuroprotection, synaptogenesis, prenatal development
MeSH terms
Adolescent, Adult, Aged, Animals, Child, Child, Preschool, Fetus, Humans, Infant, Infant, Newborn, Male, Mice, Inbred C57BL, Middle Aged, Schizophrenia, Antipsychotic Agents, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Prefrontal Cortex, Gene Expression Regulation, Developmental, Mice, Rats, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review