Effect of toxin MT-Mla isolated from M. lemniscatus snake venom on learning and memory of rats

• Grant number: 11/18969-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2012
• End date: June 30, 2012
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Maria Regina Lopes Sandoval
• Grantee: Débora da Silva Bandeira Rêgo
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The Elapidae family is constituted of 57 species are found in the Americas and three genera: Micrurus, Leptomicrurus e Micruroides. In the venom of Elapidae snakes of the genus Dendroaspis (mambas) are found neurotoxins with activity in muscarinic cholinergic receptor. Muscarínic receptors are involved in the regulation of various central nervous system functions such as autonomic, motor and sensory regulation, learning and memory, among others. Toxins of elapidaes snakes play an important role in the characterization and function of acetylcholine receptors in muscle and in the identification of muscarinic and nicotinic subtypes of receptors in the central and peripheral nervous system. In a previous study from our laboratory, we characterized the biochemical and pharmacological features of the toxin MT-Mla, isolated from M. lemmiscatus venom, which has affinity for muscarinic receptors in hippocampus and was able to displace the binding of [H3]-QNB, a selective agonist for muscarinic receptors. Thus, studying pathways of 2nd messengers that can be involved in the effects of the MT-Mla we demonstrated that this toxin was able to inhibit the increase in total inositol phosphates induced by non-selective muscarinic agonist, carbachol. We have in progress pharmacological experiments aimed to characterize the muscarinic receptor subtype involved. For functional characterization of this toxin in this project we propose to study the effects of MT-Mla in learning and memory process by methods that activate the spatial mapping of the hippocampus. We know that when activated the hippocampal muscarinic system has a facilitator role in the process of memory consolidation. (AU)