Association of Microtubule Dynamics with Chronic Epilepsy

Approximately 30 % of epilepsy cases are refractory to current pharmacological treatments through unknown mechanisms. Much work has been done on the role of synaptic components in the pathogenesis of epilepsy, but relatively little attention has been given to the potential role of the microtubules. We investigated the level of microtubule dynamic in 30 human epileptic tissues and two different chronic epilepsy rat models. The administration of microtubule-modulating agent attenuated the progression of chronic epilepsy. By contrast, microtubule-depolymerizing agent aggravated the progression of chronic epilepsy. The electrophysiological index by whole-cell clamp was used to investigate the neuronal excitation and inhibitory synaptic transmission in brain slices after administration of microtubule-modulating agent and microtubule-depolymerizing agent. Interestingly, we found that microtubule-modulating agent significantly increased the frequency of action potential firing in interneurons, and significantly promoted the amplitudes and frequencies of miniature inhibitory postsynaptic currents. Microtubule-depolymerizing agent had an opposite effect. These findings suggest that modulating hyperdynamic microtubules may take an anti-epileptic effect via postsynaptic mechanisms in interneurons. It could represent a potential pharmacologic target in epilepsy treatment.