Neuroscience 2005 Abstract
| Presentation Number: | 487.2 |
|---|---|
| Abstract Title: | Developmental regulation of NR1, NR2, and NR3 subunit expression in human parietal cortex. |
| Authors: |
Fishman, R. E.*1
; Talos, D. M.1
; Folkerth, R. D.2
; Jensen, F. E.1,3
1Neurology, Children's Hospital, Boston, MA 2Neuropathology, Children's Hospital, Boston, MA 3MA, 320 Longwood Ave., 02115, |
| Primary Theme and Topics |
Neural Excitability, Synapses, and Glia: Cellular Mechanisms - Ligand-Gated Ion Channels -- NMDA receptors: Localization |
| Secondary Theme and Topics | Disorders of the Nervous System<br />- Epilepsy<br />-- Human studies and animal models |
| Session: |
487. NMDA Receptors I Poster |
| Presentation Time: | Monday, November 14, 2005 2:00 PM-3:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # D15 |
| Keywords: | NMDA RECEPTOR, EPILEPSY, GLUTAMATE RECEPTOR, DEVELOPMENT |
The term infant is highly vulnerable to hypoxia-induced cortical neuronal injury and seizures. Animal models indicate that properties of glutamate receptor (GluR) subunits expressed in the immature brain may contribute to age-dependent increases in regional vulnerability. We showed that AMPA GluR subunits are differentially regulated in developing human and rodent neocortex consistent with the transient presence of Ca2+ permeable AMPARs on pyramidal neurons (Talos et al., SFN Abs; 2003). Rodent studies suggest developmental regulation of NMDA GluR subunits, and we hypothesized that NMDARs are also differentially expressed in human infant neocortex compared to older ages. We evaluated NMDAR subunits in parietal cortex from mid-gestation to early childhood. Western blot analysis was performed on 12 neuropathologically normal human parietal lobe autopsy samples (20-92 post-conceptional weeks (PCW) and 2 adult controls). NR1 expression does not change significantly from 20-92 PCW (p>.05). NR2A levels are low from 20-35 PCW (44% of adult, p<.001) and increase by term to 62% of adult (p<.001). NR2B levels are highest from 20-26 PCW (198%, p<.001) and are still high at term (156%, p<.005). NR2D is high at 20-21 PCW (426%, p<.001) and decreases to adult levels by term (103%, p>.05). NR3A peaks at 29-31 PCW (253%, p<.05) and is still high at term (200%, p>.05). NR2C could not be detected in these samples by western blot. There was no effect of postmortem interval. Taken together, NR2B, NR2D and NR3A subunits are overexpressed in the neonatal period. As the expression of these subunits is associated with longer NMDAR current decay and decreased sensitivity to Mg2+ block, these properties may increase susceptibility to hypoxia-induced injury and seizures at this age. Furthermore, the demonstration of age-specific subunit expression in the human provides a basis for translational therapeutic strategies for the neonatal population.
Supported by NS31718, NS38475, HD18655
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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