Upregulation of c-Kit receptor and stem cell factor in cerebellar inhibitory synapses in response to kainic acid.

Abstract

Neuronal stimulation was induced in rats by systemic administration of kainic acid (KA) to determine if such stimulation is responsible for changes in the expression patterns of c-Kit and stem cell factor (SCF) in cerebellar synapses between inhibitory interneurons and Purkinje cells. Using immunocytochemistry and immunoblotting analyses, we demonstrate that c-Kit receptor tyrosine kinase and its ligand SCF are present on the pre- and postsynaptic sides of inhibitory synapses on Purkinje cells. These proteins are upregulated during the first 48 hr after KA treatment, whereas their levels fall below that of the control by 1 week and remain as such thereafter. Expression of both c-Kit and SCF are significantly elevated in the Purkinje cell layer 24 hr after KA administration, and the Purkinje cell layer exhibits a loss of calbindin D-28K immunoreactivity. Expression of c-Kit in basket cell axon terminals is activated until 48 hr after KA treatment, suggesting the transient participation of c-Kit receptor tyrosine kinase in the maintenance of these axonal terminals. Also during the first 48 hr after KA treatment, SCF levels increase in axonal processes of Purkinje cells, and these SCF-positive axons correlate with c-Kit-positive pinceau structures. The increased expression of c-Kit and SCF in response to KA-induced neuronal stimulation may indicate that c-Kit receptor tyrosine kinase and its ligand SCF function in the inhibitory synapse between cerebellar interneurons and Purkinje cells, and that this role is most pronounced during the first 48 hr after KA treatment.