Alterations of the Cerebellar Inhibitory Interneurons and Inhibitory Synapse Following KA-induced Seizures / 대한해부학회지

Most epileptic patients have commonly suffered from recurrent seizures for many years. These seizures are usually associated with inhibitory synaptic reorganization of the hippocampal region, but it is not known whether cerebellar inhibitory synaptic changes can be induced by seizure activity. We sought to determine the pattern of cerebellar alterations in the cerebellar inhibitory interneurons (basket and stellate cells) and then tested if the alterations are associated with their synaptic transmission at the cerebellar GABAergic synapses between inhibitory interneurons and Purkinje cells after systemic kainic acid administration by immunohistochemistry, western blot analysis, dot blot analysis and confocal microscopy. A dramatic increase of the intensity of GAP-43 immunostaining was obvious in the pinceau structures following KA-induced seizures and the intense GAP-43 immunoreaction involved in high expression of PKC-sigma. The activation of the presynaptic terminal at the cerebellar inhibitory synapse is accompanied with strong GABA immunoreactivity in pinceau region (especially 48 h) after KA-seizures. These results suggest a possibility that KA-seizures increase the release of GABA at the cerebellar inhibitory presynaptic terminal and it would be contribute to the depression of Purkinje cell activity, disinhibition, during the epileptogenesis.

Roles of Stem Cell Factor and c-kit Receptor in the Development of Cerebellar GABAergic Neurons / 대한해부학회지

Evidence that Stem cell factor (SCF) and c-Kit receptor tyrosine kinase are expressed in the cerebellum during postnatal development, suggests a possible contribution of the SCF/Kit signaling pathway in the cerebellar development. In the present study, we prepared cerebellar cultures from C57Bl/6J mouse at postnatal day 1and 7 to investigate the role of c-kit receptor and SCF in regulation of growth and differentiation in the postnatal cerebellar GABAergic cells. SCF increased the number of survival cerebellar cells and density of glutamic acid decarboxylase 65/67 (GAD65/67) and calbindin D-28K expression in the immunoblot analysis. SCF also improved the neurite extension of the interneuron neuritis and dendritogenesis of Purkinje cells. Treatment with c-Kit antibody accelerated cellular loss in serum-free media and decreased the growth ability and dendritogenesis of Purkinje cells and cerebellar inhibitory interneurons. Our data suggest that SCF and c-kit receptor are required for the normal growth of postnatal cerebellum and a possible involvement of functional regulation through the SCF/c-kit receptor pathways in the postnatal cerebellar development.