Journal
EXPERIMENTAL NEUROLOGY
Volume 244, Issue -, Pages 36-42Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2011.10.028
Keywords
Temporal lobe epilepsy; GABA-A receptors; Neurosteroids; Trafficking; Physiology; Pharmacology
Categories
Funding
- NINDS NIH HHS [R01 NS040337, R01 NS044370-07, R01 NS044370, R01 NS040337-10] Funding Source: Medline
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Modification of GABAergic inhibition is an intensely investigated hypothesis guiding research into mechanisms underlying temporal lobe epilepsy (TLE). Seizures can be initiated by blocking gamma amino butyric acid type A (GABAA receptors, GABARs), which mediate fast synaptic inhibition in the brain, and controlled by drugs that enhance their function. Derivatives of steroid hormones called neurosteroids are natural substances that physiologically enhance GABAR function and suppress seizures. GABAR structure, function, expression, assembly, and pharmacological properties are changed in the hippocampus of epileptic animals. These alterations render GABARs less sensitive to neurosteroid modulation, which may contribute to seizure susceptibility. Plasticity of GABARs could play a role in periodic exacerbation of seizures experienced by women with epilepsy, commonly referred to as catamenial epilepsy. (C) 2011 Elsevier Inc. All rights reserved.
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