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

Katharina Klatte, Timo Kirschstein, David Otte, Leonie Pothmann, Lorenz Müller, Tursonjan Tokay, Maria Kober, Mischa Uebachs, Andreas Zimmer, Heinz Beck

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)13066-13080
Number of pages15
JournalJournal of Neuroscience
Volume33
Issue number32
DOIs
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Neuroscience(all)

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