Astrocytes and Epilepsy

Excerpt

Post-mortem studies of patients with temporal lobe epilepsy show that astrocytes become reactive with altered protein expression. When taken together with the observation that astrocytes release chemical transmitters the idea has developed that these glia contribute to the generation of seizures. In the epileptic brain there is a reduction in expression of an astrocyte-specific enzyme glutamine synthetase (GS) which converts synaptically released glutamate into glutamine, a precursor for glutamate and GABA synthesis. It is shown that selective reactive astrocytosis, and the accompanying loss of GS, leads to reduced synaptic inhibition and increased spread of excitation. In addition, reactive astrocytes exhibit increased expression of adenosine kinase, the enzyme responsible for converting adenosine, an endogenous anticonvulsant, to AMP. Consequently, a reduction in adenosine accompanies reactive astrocytosis. Astrocytes also regulate surface expression of neuronal NMDA receptors and contribute to their excitation through the release of glutamate and D-serine. Astrocytic Ca²⁺ signals, which are dampened by some anticonvulsants, stimulate the release of glial glutamate which can provide excitation to neurons. When this excitatory pathway is taken together with the reduction in GABA- and adenosine-dependent inhibition seen during reactive astrocytosis it is not hard to envision how these support cells might contribute to seizure generation.