Suppressed kindling epileptogenesis in mice with ectopic overexpression ofgalanin

The neuropeptide galanin has been shown to suppress epileptic seizures. In cortical and hippocampal areas, galanin is normally mainly expressed in nor adrenergic afferents. We have generated a mouse overexpressing galanin in n eurons under the platelet-derived growth factor B promoter. RIA and HPLC an alysis revealed up to 8-fold higher levels of galanin in transgenic as comp ared with wild-type mice. Ectopic galanin overexpression was detected espec ially in dentate granule cells and hippocampal and cortical pyramidal neuro ns. Galanin-overexpressing mice showed retardation of seizure generalizatio n during hippocampal kindling, a model for human complex partial epilepsy. The high levels of galanin in mossy fibers found in the transgenic mice wer e further increased after seizures. Frequency facilitation of field excitat ory postsynaptic potentials, a form of short-term synaptic plasticity asses sed in hippocampal slices, was reduced in mossy fiber-CA3 cell synapses of galanin-overexpressing mice, indicating suppressed glutamate release. This effect was reversed by application of the putative galanin receptor antagon ist M35. These data provide evidence that ectopically overexpressed galanin can be released and dampen the development of epilepsy by means of recepto r-mediated action, at least partly by reducing glutamate release from mossy fibers.