Peer Reviewed

1

Document Type

Article

Publication Date

1-6-2014

Keywords

Adult Stem Cells, Animals, Cell Proliferation, Hippocampus, In Situ Nick-End Labeling, Male, Mice, Mice, Inbred C57BL, Neural Stem Cells, Neurogenesis, Piperidines, Receptors, N-Methyl-D-Aspartate

Funder/Sponsor

This work was supported by grants from Science Foundation Ireland to JHMP (03/RP1/B344;08/INI/1949) and by the School of Pharmacy, RCSI.

Comments

This article is also available at http://onlinelibrary.wiley.com/doi/10.1002/jnr.23347/epdf

Abstract

The N-methyl-D-aspartate (NMDA) receptor, one of the ionotropic glutamate receptor, plays important physiological and pathological roles in learning and memory, neuronal development, acute and chronic neurological diseases, and neurogenesis. This work examines the contribution of the NR2B NMDA receptor subunit to adult neurogenesis/cell proliferation under physiological conditions and following an excitotoxic insult. We have previously shown in vitro that a discrete NMDA-induced, excitotoxic injury to the hippocampus results in an increase in neurogenesis within the dentate gyrus. Here we have characterized adult neurogenesis or proliferation, using BrdU, in an in vivo model of excitotoxic injury to the CA1 subfield of the hippocampus. We demonstrate a peak in neural stem cell proliferation/neurogenesis between 6 and 9 days after the excitotoxic insult. Treatment with ifenprodil, an NR2B subunit-specific NMDA receptor antagonist, without prior injury induction, also increased the number of BrdU-positive cells within the DG and posterior periventricle, indicating that ifenprodil itself could modulate the rate of proliferation. Interestingly, though, the increased level of cell proliferation did not change significantly when ifenprodil was administered following an excitotoxic insult. In conclusion, our results suggest and add to the growing evidence that NR2B subunit-containing NMDA receptors play a role in neural stem cell proliferation.

Disciplines

Pharmacy and Pharmaceutical Sciences

Citation

Bunk EC, König H-G, Prehn JH, Kirby BP. Effect of the N-methyl-D-aspartate NR2B subunit antagonist ifenprodil on precursor cell proliferation in the hippocampus. Journal of Neuroscience Research. 2014;92(6):679-91.

PubMed ID

24464409

DOI Link

10.1002/jnr.23347

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

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