ABSTRACT
Aims: TsTX-I scorpion toxin, also known as ã-toxin, is a â-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.
Subject(s)
Animals , Scorpion Venoms/adverse effects , Scorpion Venoms/toxicity , Hippocampus , InjectionsABSTRACT
Tityus serrulatus and Tityus bahiensis are considered to be the most venomous scorpions in Brazil and are responsible for most of the accidents that occur in our country. The main toxic agents in scorpion venoms are small basic polypeptides that act as neurotoxins. They cause a derangement of ion channels that result in abnormal release of neurotransmitters. In the present study we fractionated the venom of Tityus bahiensis and studied the effects of fractions P2, P3, P4, P5, P6 and P7, on the mammalian central nervous system. Intravenous injection of P5, P6 and P7 in rats induced spontaneous convulsion, intrahippocampal injection caused behavioural seizures, and P5 and P6 induced electrographic seizures. P5 caused neuronal damage in the CA1 area and P6 in the CA1, CA3 areas and hilus of the dentate gyrus (DG) of the hippocampus. Injection of P3 in the hippocampus did not induce convulsions or lesions. However, when injected intravenously in mice, this fraction reduced behavioural activity in an open field test. Unilateral injection of P4 in the hippocampus caused neuronal damage in the contralateral CA3, but not in the ipsilateral hippocampus. These results suggest that scorpion toxins present in the venom are able to act directly on the central nervous system promoting behavioural and histopathological effects.
Subject(s)
Neurotoxins/toxicity , Scorpion Venoms/toxicity , Animals , Behavior, Animal/drug effects , Convulsants/toxicity , Electroencephalography/drug effects , Hippocampus/drug effects , Hippocampus/pathology , Injections , Injections, Intravenous , Male , Mice , Neurons/drug effects , Rats , Rats, WistarABSTRACT
Tityus serrulatus and Tityus bahiensis are considered to be the most venomous scorpions in Brazil and are responsible for most of the accidents that occur in our country. The main toxic agents in scorpion venoms are small basic polypeptides that act as neurotoxins. They cause a derangement of ion channels that result in abnormal release of neurotransmitters. In the present study we fractionated the venom of Tityus bahiensis and studied the effects of fractions P2, P3, P4, P5, P6 and P7, on the mammalian central nervous system. Intravenous injection of P5, P6 and P7 in rats induced spontaneous convulsion, intrahippocampal injection caused behavioural seizures, and P5 and P6 induced electrographic seizures. P5 caused neuronal damage in the CA1 area and P6 in the CA1, CA3 areas and hilus of the dentate gyrus (DG) of the hippocampus. Injection of P3 in the hippocampus did not induce convulsions or lesions. However, when injected intravenously in mice, this fraction reduced behavioural activity in an open field test. Unilateral injection of P4 in the hippocampus caused neuronal damage in the contralateral CA3, but not in the ipsilateral hippocampus. These results suggest that scorpion toxins present in the venom are able to act directly on the central nervous system promoting behavioural and histopathological effects.
Subject(s)
Male , Female , Humans , Animals , Scorpion Venoms/adverse effects , Scorpion Venoms/toxicity , NeurotoxinsABSTRACT
Scorpion venoms contain low molecular weight basic polypeptides, neurotoxins, that are the principal toxicagents. These toxins act on ion channels, promoting a derangement that may result in an abnormal release of neurotransmitters.In the present study we investigated some of the effects of the F, H and J fractions isolated from Tityus serrulatusscorpion venom on the central nervous system of rodents. The venom was partially purified by gel filtration chromatography.The neurotoxic effect of these fractions was studied on convulsive activity after intravenous injection, and on electrographicactivity and neuronal integrity of rat hippocampus when injected directly into this brain area. The results showedthat intravenous injection of the F and H fractions induced convulsions, and intrahippocampal injection caused electrographicseizures in rats and neuronal damage in specific hippocampal areas. Fraction J injected intravenously reduced thegeneral activity of mice in the open field but induced no changes when injected into the brain. These results suggest thatscorpion toxins are able to act directly on the central nervous system promoting behavioural, electrographic and histologicalmodifications.
Subject(s)
Male , Female , Humans , Animals , Scorpion Venoms/classification , Scorpion Venoms/toxicityABSTRACT
The effect of lithium (2.0 mEq/kg, IP) on dopaminergic supersensitivity induced by long-term estrogen treatment (0.25 mg/day, SC) was investigated. Ovariectomized rats were treated for 28 days with estrogen and/or lithium and 6 days after the last administration all animals were observed for apomorphine-induced stereotyped behavior (1.0 mg/kg, SC). The abrupt withdrawal from long-term estrogen treatment increased rats' sensitivity to apomorphine but lithium administration was able to prevent this increase. Lithium alone produced no effect on stereotyped behavior. It was suggested that lithium may antagonize the estrogen effect on the nigrostriatal dopamine system.
