Impaired D-serine-mediated cotransmission mediates cognitive dysfunction in epilepsy.
J Neurosci
; 33(32): 13066-80, 2013 Aug 07.
Article
em En
| MEDLINE
| ID: mdl-23926260
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Serina
/
Transtornos Cognitivos
/
Transmissão Sináptica
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Agonistas de Aminoácidos Excitatórios
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Epilepsia do Lobo Temporal
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Hipocampo
Tipo de estudo:
Etiology_studies
Idioma:
En
Revista:
J Neurosci
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Alemanha