Hippocampal Hyperexcitability is Modulated by Microtubule-Active Agent: Evidence from In Vivo and In Vitro Epilepsy Models in the Rat

摘要: The involvement of microtubule dynamics on bioelectric activity neurons and neurotransmission represents a fascinating target research in the context neural excitability. It has been reported that alteration cytoskeleton can lead to profound modifications functioning, with putative impact hyperexcitability phenomena. Altogether, present study we pointed at exploring outcomes modulating degree polymerization two electrophysiological epileptiform rat hippocampus. To this aim, used vivo Maximal Dentate Activation (MDA) vitro hippocampal bursting (HEBA) paradigms assess effects nocodazole paclitaxel, respectively destabilize stabilize structures. In particular, MDA paroxysmal discharge is electrically induced, whereas HEBA obtained by altering extracellular ionic concentrations. Our results provided evidence 10 µM was able reduce severity seizures, without inducing neurotoxicity as verified immunohistochemical assay. some cases, completely blocked during maximal effect drug. These data were also agreement HEBA, since markedly decreased burst even silenced occasionally. contrast, paclitaxel did not exert clear action both paradigms. study, targeting cellular mechanisms much considered so far, suggests possibility microtubule-active drugs could modulate brain hyperexcitability. This contributes hypothesis function may affect synaptic processes, relapsing aspects epileptic activity.