Skip Navigation



Cerebral Cortex Advance Access published online on February 21, 2008
Cerebral Cortex, doi:10.1093/cercor/bhn017
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Henson, M. A.
Right arrow Articles by Philpot, B. D.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Henson, M. A.
Right arrow Articles by Philpot, B. D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Developmental Regulation of the NMDA Receptor Subunits, NR3A and NR1, in Human Prefrontal Cortex

Maile A. Henson1, Adam C. Roberts2,3, Kayvon Salimi4, Swarooparani Vadlamudi4, Robert M. Hamer4,5,6, John H. Gilmore1,4,5, L. Fredrik Jarskog7,8 and Benjamin D. Philpot1,2,3

1 Curriculum in Neurobiology, 2 Neuroscience Center, 3 Department of Cell and Molecular Physiology, 4 Department of Psychiatry, 5 Schizophrenia Research Center, 6 Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27705, USA, 7 Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 8 Department of Psychiatry, Columbia University, New York, NY 10032, USA

Address correspondence to Benjamin D. Philpot, University of North Carolina, Campus Box 7545, 115 Mason Farm Road, Chapel Hill, NC 27599-7545, USA. Email: bphilpot{at}med.unc.edu.

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.

Key Words: antipsychotic • DLPFC • glutamate • postmortem • schizophrenia


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.