Impaired D-Serine-Mediated cotransmission mediates cognitive dysfunction in epilepsy
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Date
2013-08-07
Authors
Klatte, Katharina
Kirschstein, Timo
Otte, David
Pothmann, Leonie
Muller, Lorenz
Tokay, Tursonjan
Kober, Maria
Uebachs, Mischa
Zimmer, Andreas
Beck, Heinz
Journal Title
Journal ISSN
Volume Title
Publisher
Neurobiology of Disease
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.
Description
Keywords
Epilepsy, D-serine, NMDAR, Research Subject Categories::MEDICINE