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Developmental Expression of N-Methyl-D-Aspartate (NMDA) Receptor Subunits in Human White and Gray Matter: Potential Mechanism of Increased Vulnerability in the Immature Brain

Title
Developmental Expression of N-Methyl-D-Aspartate (NMDA) Receptor Subunits in Human White and Gray Matter: Potential Mechanism of Increased Vulnerability in the Immature Brain
Author
박현경
Keywords
xcitotoxicity; glutamate; hypoxia-ischemia; N-methyl-d-aspartate; periventricular leukomalacia.
Issue Date
2013-09
Publisher
Oxford University Press
Citation
Cerebral cortex, Vol.25 No.2 [2015], 482-495
Abstract
The pathophysiology of perinatal brain injury is multifactorial and involves hypoxia-ischemia (HI) and inflammation. N -methyl- d -aspartate receptors (NMDAR) are present on neurons and glia in immature rodents, and NMDAR antagonists are protective in HI models. To enhance clinical translation of rodent data, we examined protein expression of 6 NMDAR subunits in postmortem human brains without injury from 20 postconceptional weeks through adulthood and in cases of periventricular leukomalacia (PVL). We hypothesized that the developing brain is intrinsically vulnerable to excitotoxicity via maturation-specific NMDAR levels and subunit composition. In normal white matter, NR1 and NR2B levels were highest in the preterm period compared with adult. In gray matter, NR2A and NR3A expression were highest near term. NR2A was significantly elevated in PVL white matter, with reduced NR1 and NR3A in gray matter compared with uninjured controls. These data suggest increased NMDAR-mediated vulnerability during early brain development due to an overall upregulation of individual receptors subunits, in particular, the presence of highly calcium permeable NR2B-containing and magnesium-insensitive NR3A NMDARs. These data improve understanding of molecular diversity and heterogeneity of NMDAR subunit expression in human brain development and supports an intrinsic prenatal vulnerability to glutamate-mediated injury; validating NMDAR subunit-specific targeted therapies for PVL.
URI
https://academic.oup.com/cercor/article/25/2/482/303001http://hdl.handle.net/20.500.11754/46076
ISSN
1047-3211
DOI
10.1093/cercor/bht246
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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