Impaired D-Serine-Mediated cotransmission mediates cognitive dysfunction in epilepsy
| dc.contributor.author | Klatte, Katharina | |
| dc.contributor.author | Kirschstein, Timo | |
| dc.contributor.author | Otte, David | |
| dc.contributor.author | Pothmann, Leonie | |
| dc.contributor.author | Muller, Lorenz | |
| dc.contributor.author | Tokay, Tursonjan | |
| dc.contributor.author | Kober, Maria | |
| dc.contributor.author | Uebachs, Mischa | |
| dc.contributor.author | Zimmer, Andreas | |
| dc.contributor.author | Beck, Heinz | |
| dc.date.accessioned | 2016-02-03T03:21:01Z | |
| dc.date.available | 2016-02-03T03:21:01Z | |
| dc.date.issued | 2013-08-07 | |
| dc.description.abstract | The modulation of synaptic plasticity by NMDA receptor (NMDAR)-mediated processes is essential for many forms of learning and memory. Activation of NMDARs by glutamate requires the binding of a coagonist to a regulatory site of the receptor. In many forebrain regions, this coagonist is D-serine. Here, we show that experimental epilepsy in rats is associated with a reduction in the CNS levels of D-serine, which leads to a desaturation of the coagonist binding site of synaptic and extrasynaptic NMDARs. In addition, the subunit composition of synaptic NMDARs changes in chronic epilepsy. The desaturation of NMDARs causes a deficit in hippocampal long-term potentiation, which can be rescued with exogenously supplied D-serine. Importantly, exogenous D-serine improves spatial learning in epileptic animals. These results strongly suggest that D-serine deficiency is important in the amnestic symptoms of temporal lobe epilepsy. Our results point to a possible clinical utility of D-serine to alleviate these disease manifestations. | ru_RU |
| dc.identifier.uri | http://nur.nu.edu.kz/handle/123456789/1130 | |
| dc.language.iso | en | ru_RU |
| dc.publisher | Neurobiology of Disease | ru_RU |
| dc.rights | Attribution-NonCommercial-NoDerivs 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/us/ | * |
| dc.subject | Epilepsy | ru_RU |
| dc.subject | D-serine | ru_RU |
| dc.subject | NMDAR | ru_RU |
| dc.subject | Research Subject Categories::MEDICINE | ru_RU |
| dc.title | Impaired D-Serine-Mediated cotransmission mediates cognitive dysfunction in epilepsy | ru_RU |
| dc.type | Article | ru_RU |