Klatte, KatharinaKirschstein, TimoOtte, DavidPothmann, LeonieMuller, LorenzTokay, TursonjanKober, MariaUebachs, MischaZimmer, AndreasBeck, Heinz2016-02-032016-02-032013-08-07http://nur.nu.edu.kz/handle/123456789/1130The 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.enAttribution-NonCommercial-NoDerivs 3.0 United StatesEpilepsyD-serineNMDARResearch Subject Categories::MEDICINEArticle