PMID- 18296432
OWN - NLM
STAT- MEDLINE
DCOM- 20081222
LR  - 20211020
IS  - 1460-2199 (Electronic)
IS  - 1047-3211 (Print)
IS  - 1047-3211 (Linking)
VI  - 18
IP  - 11
DP  - 2008 Nov
TI  - Developmental regulation of the NMDA receptor subunits, NR3A and NR1, in human 
      prefrontal cortex.
PG  - 2560-73
LID - 10.1093/cercor/bhn017 [doi]
AB  - 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.
FAU - Henson, Maile A
AU  - Henson MA
AD  - Curriculum in Neurobiology, University of North Carolina, Chapel Hill, NC 27705, 
      USA.
FAU - Roberts, Adam C
AU  - Roberts AC
FAU - Salimi, Kayvon
AU  - Salimi K
FAU - Vadlamudi, Swarooparani
AU  - Vadlamudi S
FAU - Hamer, Robert M
AU  - Hamer RM
FAU - Gilmore, John H
AU  - Gilmore JH
FAU - Jarskog, L Fredrik
AU  - Jarskog LF
FAU - Philpot, Benjamin D
AU  - Philpot BD
LA  - eng
GR  - R01 EY018323/EY/NEI NIH HHS/United States
GR  - R01 EY018323-02/EY/NEI NIH HHS/United States
GR  - MH064065/MH/NIMH NIH HHS/United States
GR  - 2R25GM055336/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080221
PL  - United States
TA  - Cereb Cortex
JT  - Cerebral cortex (New York, N.Y. : 1991)
JID - 9110718
RN  - 0 (Antipsychotic Agents)
RN  - 0 (NR1 NMDA receptor)
RN  - 0 (NR2A NMDA receptor)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (NR3A NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Antipsychotic Agents/pharmacology/therapeutic use
MH  - Child
MH  - Child, Preschool
MH  - Fetus
MH  - *Gene Expression Regulation, Developmental
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Middle Aged
MH  - Prefrontal Cortex/embryology/*growth & development/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*genetics/metabolism
MH  - Schizophrenia/drug therapy/*physiopathology
MH  - Young Adult
PMC - PMC2733318
EDAT- 2008/02/26 09:00
MHDA- 2008/12/23 09:00
PMCR- 2009/11/01
CRDT- 2008/02/26 09:00
PHST- 2008/02/26 09:00 [pubmed]
PHST- 2008/12/23 09:00 [medline]
PHST- 2008/02/26 09:00 [entrez]
PHST- 2009/11/01 00:00 [pmc-release]
AID - bhn017 [pii]
AID - 10.1093/cercor/bhn017 [doi]
PST - ppublish
SO  - Cereb Cortex. 2008 Nov;18(11):2560-73. doi: 10.1093/cercor/bhn017. Epub 2008 Feb 
      21.