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

20 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
Externally publishedYes

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Serine
Epilepsy
Neuronal Plasticity
Temporal Lobe Epilepsy
Long-Term Potentiation
Prosencephalon
N-Methyl-D-Aspartate Receptors
Cognitive Dysfunction
Glutamic Acid
Binding Sites
Learning

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Klatte, K., Kirschstein, T., Otte, D., Pothmann, L., Müller, L., Tokay, T., ... Beck, H. (2013). Impaired D-Serine-Mediated cotransmission mediates cognitive dysfunction in epilepsy. Journal of Neuroscience, 33(32), 13066-13080. https://doi.org/10.1523/jneurosci.5423-12.2013

Impaired D-Serine-Mediated cotransmission mediates cognitive dysfunction in epilepsy. / Klatte, Katharina; Kirschstein, Timo; Otte, David; Pothmann, Leonie; Müller, Lorenz; Tokay, Tursonjan; Kober, Maria; Uebachs, Mischa; Zimmer, Andreas; Beck, Heinz.

In: Journal of Neuroscience, Vol. 33, No. 32, 2013, p. 13066-13080.

Research output: Contribution to journalArticle

Klatte, K, Kirschstein, T, Otte, D, Pothmann, L, Müller, L, Tokay, T, Kober, M, Uebachs, M, Zimmer, A & Beck, H 2013, 'Impaired D-Serine-Mediated cotransmission mediates cognitive dysfunction in epilepsy', Journal of Neuroscience, vol. 33, no. 32, pp. 13066-13080. https://doi.org/10.1523/jneurosci.5423-12.2013
Klatte, Katharina ; Kirschstein, Timo ; Otte, David ; Pothmann, Leonie ; Müller, Lorenz ; Tokay, Tursonjan ; Kober, Maria ; Uebachs, Mischa ; Zimmer, Andreas ; Beck, Heinz. / Impaired D-Serine-Mediated cotransmission mediates cognitive dysfunction in epilepsy. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 32. pp. 13066-13080.
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