N-Methyl d-Aspartate Receptor Expression Patterns in the Human Fetal Cerebral Cortex

N-methyl d-aspartate receptors (NMDARs), a subtype of glutamate receptor, have important functional roles in cellular activity and neuronal development. They are well-studied in rodent and adult human brains, but limited information is available about their distribution in the human fetal cerebral c...

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Published in:Cerebral cortex (New York, N.Y. 1991) N.Y. 1991), 2017-11, Vol.27 (11), p.5041-5053
Main Authors: Bagasrawala, Inseyah, Memi, Fani, V Radonjic, Nevena, Zecevic, Nada
Format: Article
Language:English
Subjects:
Blotting, Western
Cerebral Cortex - cytology
Cerebral Cortex - embryology
Cerebral Cortex - metabolism
gamma-Aminobutyric Acid - metabolism
Gene Expression Regulation, Developmental
Glutamic Acid - metabolism
Humans
Immunohistochemistry
In Situ Hybridization
Neural Stem Cells - cytology
Neural Stem Cells - metabolism
Neurons - cytology
Neurons - metabolism
Original
Polymerase Chain Reaction
Receptors, N-Methyl-D-Aspartate - metabolism
RNA, Messenger - metabolism
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Summary:N-methyl d-aspartate receptors (NMDARs), a subtype of glutamate receptor, have important functional roles in cellular activity and neuronal development. They are well-studied in rodent and adult human brains, but limited information is available about their distribution in the human fetal cerebral cortex. Here we show that 3 NMDAR subunits, NR1, NR2A, and NR2B, are expressed in the human cerebral cortex during the second trimester of gestation, a period of intense neurogenesis and synaptogenesis. With increasing fetal age, expression of the NMDAR-encoding genes Grin1 (NR1) and Grin2a (NR2A) increased while Grin2b (NR2B) expression decreased. The protein levels of all 3 subunits paralleled the changes in gene expression. On cryosections, all 3 subunits were expressed in proliferative ventricular and subventricular zones, in radial glia, and in intermediate progenitor cells, consistent with their role in the proliferation of cortical progenitor cells and in the determination of their respective fates. The detection of NR1, NR2A, and NR2B in both glutamatergic and GABAergic neurons of the cortical plate suggests the involvement of NMDARs in the maturation of human cortical neurons and in early synapse formation. Our results and previous studies in rodents suggest that NMDAR expression in the developing human brain is evolutionarily conserved.
ISSN:1047-3211
1460-2199
DOI:10.1093/cercor/bhw289