The study of the mediation of Ohanin, a king cobra (Ophiophagus Hannah) toxin through the central nervous system

Abstract

Ohanin, a 12 kDa novel protein from king cobra venom induces hypolocomotion and hyperalgesia in mice. Recombinant ohanin and its precursor pro-ohanin are nontoxic up to 10 mg/kg when injected intraperitoneally in mice. Unlike ohanin, pro-ohanin did not show dose-dependent hypolocomotion when administered intraperitoneally. However, both proteins induced potent hypolocomotory effect when injected intracerebroventricularly, suggesting their direct action on CNS. To identify the site of action in mouse brain, ex vivo and in vivo binding studies using recombinant ohanin and pro-ohanin were performed. Both proteins specifically bind to hippocampus and cerebellum regions that control and co-ordinate locomotion. Intraperitoneally administered ohanin appears to cross the blood-brain barrier more efficiently than pro-ohanin, indicating the physiological relevance of its maturation for efficient induction of hypolocomotion in prey. Our results demonstrate efficient transportation of ohanin across the intact blood-brain barrier and binding to hippocampal and cerebellar regions to induce CNS-mediated hypolocomotion in mice.