A infusão intrahipocampal da crotamina isolada do veneno da crotalus durissus terrificus promove a persistência da memória e altera parâmetros bioquímicos em ratos

Abstract

The crotamine, a toxin isolated from the venom of Crotalus durissus terrificus (Cdt) is a polypeptide myotoxin, nonenzymatic, with basic character, which is composed of 42 amino acid residues with a molecular weight of 4,880 daltons. Known to induce depolarization of skeletal muscle by increasing membrane permeability to sodium ions, studies have shown that this toxin is able to promote the release of acetylcholine and dopamine in the central nervous system of rats. Particularly, these neurotransmitters are important modulators in the process of memory formation. Considering the importance of these neurotransmitters in mnemonic processes, it becomes interesting to study substances who can act on them, thereby modulating the mnemonic processes often hampered by various cognitive dysfunctions of the central nervous system. Thus, this study investigated the effects of intrahippocampal infusion of crotamine in persistence of memory and in hematological and oxidative stress parameters in rats. 40 male Wistar rats 3 months aged were used. The experiments were performed in two stages. In step 1, after the implantation of hippocampal cannulae, the sample was divided into two groups: experimental and control. Both were trained in the object recognition (OR) and inhibitory avoidance (IA) task to verify the effects of crotamine on consolidation and persistence of recognition and aversive memories, in step 2 were performed the evaluations of hematological and oxidative stress parameters. The infusion of crotamine (1μg/μl, 1μl/lado) improved the persistence of recognition memory (object recognition task) and aversive memory (inhibitory avoidance task), both tested 24 hours, 7, 14 and 21 days after training and toxin infusion. However, the toxin promoted inflammation and toxicity as demonstrated by serum changes in hematological and oxidative stress parameters. These results demonstrate a remarkable possibility of using crotamine as a pharmacological tool in diseases involving impairment of memory persistence, such as dementias, however, additional research is needed in order to seek alternatives that minimize the toxic effects of crotamine, enabling the its use.