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Impaired D-Serine-Mediated cotransmission mediates cognitive dysfunction in epilepsy

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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.identifier.uri http://nur.nu.edu.kz/handle/123456789/1130
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.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

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