L22 Intranasal application of NPY and NPY13–36 ameliorate disease pathology in R6/2 mouse model of huntington’s disease

Background Neuropeptide Y (NPY) is a potent neuromodulator that is expressed throughout the central nervous system. The sparing and persistence increase in NPY-expressing striatal interneurons with advancing disease have been implicated to correlate with striatal pathology in both Huntington’s disease (HD) patients and animal models of HD. However, the potential roles of intense expression of NPY in HD pathology still remain under-explored. Aims To investigate whether activation of NPY-Y2 receptor using NPY and selective Y2 receptor ligands could ameliorate behavioural deficits and neuropathology in R6/2 mouse model of HD. Methods/techniques NPY and selective Y2 receptor agonist NPY13-36 were intranasally administered to R6/2 mice, five days in a week, beginning from 4 weeks of age until 12 weeks of age. In the second study, R6/2 mice received daily intraperitoneal administration of selective non-peptide Y2 receptor antagonist (SF-31) to selectively block Y2 receptor. Results/outcome Intranasal application of NPY showed significant increase in rotarod performance compared to saline and SF-31 treated R6/2 mice (pp Conclusion Taken together, our findings suggest that targeting NPY-Y2 receptor might be a potential neuroprotective therapy for HD and other neurodegenerative diseases.