Intrahippocampal injection of TsTX-I, a beta-scorpion toxin, causes alterations in electroencephalographic recording and behavior in rats

Abstract

Aims TsTX-I scorpion toxin, also known as γ-toxin, is a β-toxin which binds to site 4 of the sodium channel, shifting its activation potential. There are few studies about its pharmacological action in the central nervous system. The objective of this work was to determine the electroencephalographic, behavioral and histopathological effects of intrahippocampal injection of TsTX-I. Main methods Rats were anesthetized and fitted with cannulae for injection into the hippocampus and with electrodes for cerebral recording. The animals were treated with Ringer solution, some doses of TsTX-I, DMSO 0.1% or veratridine. Behavioral and electrographic recordings were observed for 4 hours after the injection. After 7 days, the rats were perfused, and their brains removed for histological analysis. Key findings Increasing doses of the toxin evoked epileptic-like discharges, wet dog shakes, and in some cases hind limb paralysis and intense respiratory difficulty followed by death. The histopathological analysis demonstrated no cell loss. Animals injected with veratridine developed epileptiform activity in the electrographic recording and neuronal loss. Significance The results suggest that TsTX-I toxin may be responsible, at least in part, for the epileptic and behavioral effects observed with the crude venom, and although veratridine and TsTX-I act on Na-channel, the differences between them are remarkable, demonstrating that toxins can have different functional effects depending on the site of action in the channel. Thus, animal neurotoxins are often highly selective and may be useful for the identification of the sequence of events underlying neurotransmission.