Up-regulation Of Dysbindin In Temporal Lobe Pileptic Foci Of Human And Experimental Nimals

The gene encoding dystrobrevin-binding-protein-1(dysbindin) isexpressed in many areas of the central nervous system and plays a role inintracellular vesicle trafficking, synaptic vesicle trafficking andneurotransmitter release. At a cellular level, dysbindin is thought to mediatepresynaptic glutamatergic transmission. The occurrence of epilepsy isrelated to an imbalance between excitation and inhibition neurotransmittersin the brain. Glutamate is the most abundant excitatory neurotransmitter inthe brain and, as such, it inevitably plays a role in the initiation and spread ofseizure activity. Using Western blotting and immunofluorescence, weinvestigated dysbindin expression in brain tissues of the patients withtemporal lobe epilepsy (TLE) and rats with temporal lobe epilepsy (lithiumchloridepilocarpine model) to explore its possible role in epileptogenesis.Twenty-five samples of temporal neocortex from patients undergoingsurgery for drug-refractory TLE epilepsy and ten histologically normaltemporal lobes tissues from control patients were used in our study. We alsoexamined dysbindin expression in the hippocampus and adjacent cortex from experimental Sprague–Dawley rats. Dysbindin was expressed in thecytoplasm of neurons from epileptic specimens, and levels of dysbindinproteins were significantly increased in patients with TLE. Dysbindin wasalso expressed in the neurons of the hippocampus and adjacent cortex fromexperimental and control rats. Western blotting of rat brain tissue showedthat dysbindin was upregulated gradually from6hours after kindling.Maximal expression was seen around2months in chronic epileptic phase.These results demonstrated that the increased expression of dysbindin mayplay a role in the pathogenesis of drug-refractory TLE.