Vesicular glutamate transporters as innovative drug targets for future anti-epileptic drugs

Project Details

Description

The epilepsies are major neurological disorders that hit approximately 1% of the worldwide population. Temporal lobe epilepsy is a form of limbic epilepsy that remains difficult to treat with the current available medication. Pharmacoresistance to the various antiepileptic drugs (AEDs) occurs in 25-40% of the patients suffering from temporal lobe epilepsy. All AEDs symptomatically suppress the occurrence of seizures but do not treat the cause of seizure generation. In order to probe potential new pharmacological targets, we will study systematically the involvement of vesicular glutamate transporters in the different developmental stages of the chronic pilocarpine rodent model for limbic epilepsy. The techniques that we will use are 24 h video monitoring combined with telemetry for electroencephalographic (EEG) registration, Western blotting for semi-quantitative determination of the transporter proteins and immunohistochemistry for studying possible changes in distribution of the different transporter subtypes. Knockout mice for the different transporters will be used to study differences in susceptibility to seizure induction between wild-type and transgenic mice. These studies will not only unravel the involvement and/or importance of one or more of these glutamate transporters in the process of epileptogenesis but will probably also lead to innovative drug targets for future compounds with anticonvulsant or even anti-epileptogenic effects.
AcronymFWOTM428
StatusFinished
Effective start/end date1/10/0730/09/11

Keywords

  • epilepsy
  • glutamate transporters
  • pharmacology

Flemish discipline codes

  • Basic sciences