Epileptic responses in marmosets induced by knockdown of CREB Regulated Transcription Coactivator 1 (CRTC1)

Abstract

Epilepsy is a major neurological disorder. Despite the major contribution of animal models to the development of anticonvulsant drugs, 20-30% of epilepsy patients still fail to achieve adequate seizure control. Novel animal models are needed for the development of new drugs. Here we report CRTC1 KD-induced epileptic response by short hairpin (shRNA) RNA injection into marmoset V1. Three local injections of shCRTC1 induced cFOS expression beyond the injection sites. Real-time analysis of cortical electrocorticography revealed transient changes in high frequency oscillations throughout the cortex, and a second lesion was observed in the temporal lobe by MRI and post-mortem histology. shCRTC1 knockdown marmosets showed severe lesions surrounding the injection site several months after the injection, while glial cell activations appeared even before IEG induction could be detected one month after the shCRTC1 injection. These features suggest the utility of the shCRTC1 KD marmoset in the study of focal and structural epilepsy.