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Effect of the N-methyl-D-aspartate NR2B subunit antagonist ifenprodil on precursor cell proliferation in the hippocampus.

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posted on 22.11.2019 by Eva C. Bunk, Hans-Georg König, Jochen HM Prehn, Brian P. Kirby

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.

Funding

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.

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

Published 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.

Publication Date

01/06/2014

Publisher

Wiley Interscience

PubMed ID

24464409

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