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The N-methyl-d-aspartate receptor modulator GLYX-13 enhances learning and memory, in young adult and learning impaired aging rats
| Content Provider | Semantic Scholar |
|---|---|
| Author | Burgdorf, Jeffrey Zhang, Xiao-Lei Weiss, Craig Matthews, Elizabeth Moskal, Joseph R. |
| Copyright Year | 2011 |
| Abstract | NMDA receptor (NMDAR) activity has been strongly implicated in both in vitro and in vivo learning models and the decline in cognitive function associated with aging and is linked to a decrease in NMDAR functional expression. GLYX-13 is a tetrapeptide (Thr-Pro-Pro-Thr) which acts as a NMDAR receptor partial agonist at the glycine site. GLYX-13 was administered to young adult (3 months old) and aged (27-32 months old) Fischer 344 X Brown Norway F1 rats (FBNF1), and behavioral learning tested in trace eye blink conditioning (tEBC), a movable platform version of the Morris water maze (MWM), and alternating t-maze tasks. GLYX-13 (1mg/kg, i.v.) enhanced learning in both young adult and aging animals for MWM and alternating t-maze, and increased tEBC in aging rats. We previously showed optimal enhancement of tEBC in young adult rats given GLYX-13 at the same dose. Of these learning tasks, the MWM showed the most robust age related deficit in learning. In the MWM, GLYX-13 enhancement of learning was greater in the old compared to the young adult animals. Examination of the induction of long-term potentiation (LTP) and depression (LTD) at Schaffer collateral-CA1 synapses in hippocampal slices showed that aged rats showed marked, selective impairment in the magnitude of LTP evoked by a sub-maximal tetanus, and that GLYX-13 significantly enhanced the magnitude of LTP in slices from both young adult and aged rats without affecting LTD. These data, combined with the observation that the GLYX-13 enhancement of learning was greater in old than in young adult animals, suggest that GLYX-13 may be a promising treatment for deficits in cognitive function associated with aging. |
| Starting Page | 698 |
| Ending Page | 706 |
| Page Count | 9 |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/j.neurobiolaging.2009.04.012 |
| PubMed reference number | 19446371 |
| Journal | Medline |
| Volume Number | 32 |
| Alternate Webpage(s) | http://www.mccormick.northwestern.edu/research/molecular-therapeutics-falk-center/documents/publications/the-n-methyl-d-aspartate-receptor-modulator.pdf |
| Alternate Webpage(s) | http://www.mccormick.northwestern.edu/research/molecular-therapeutics-falk-center/documents/nmda-receptor-modulator.pdf |
| Alternate Webpage(s) | https://www.sciencedirect.com/science/article/pii/S0197458009001389?dgcid=api_sd_search-api-endpoint |
| Alternate Webpage(s) | http://falk.mccormick.northwestern.edu/doc/14TheNmethylDAspartateReceptorModulator.pdf |
| Alternate Webpage(s) | https://api.elsevier.com/content/article/pii/S0197458009001389 |
| Alternate Webpage(s) | https://doi.org/10.1016/j.neurobiolaging.2009.04.012 |
| Journal | Neurobiology of Aging |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
