Tb1, a Neurotoxin from Tityus bahiensis Scorpion Venom, Induces Epileptic Seizures by Increasing Glutamate Release

Abstract

Here, we report the neurotoxic effects aroused by the intracerebral injection (in rats) of Tb1, which is a neurotoxin isolated from Tityus bahiensis scorpion venom. Biochemical analyses have demonstrated that this toxin is similar to the gamma toxin from T. serrulatus, which is a β-scorpion toxin that acts on sodium channels, causing the activation process to occur at more hyperpolarized membrane voltages. Male Wistar rats were stereotaxically implanted with intrahippocampal electrodes and cannulas for electroencephalographic recording and the evaluation of amino acid neurotransmitters levels. Treated animals displayed behavioral and electroencephalographic alterations similar to epileptiform activities, such as myoclonus, wet dog shakes, convulsion, strong discharges, neuronal loss, and increased intracerebral levels of glutamate. Scorpion toxins are important pharmacological tools that are widely employed in ion channel dysregulation studies. The current work contributes to the understanding of channelopathies, particularly epilepsy, which may originate, among other events, from dysfunctional sodium channels, which are the main target of the Tb1 toxin.

Dopaminergic metabolism is affected by intracerebral injection of Tb II-I isolated from Tityus bahiensis scorpion venom

“…Isolated toxins from Tb venom have not yet been fully characterized and their effects on the central nervous system (CNS) are poorly understood. Some studies have demonstrated that peripheral Tb crude venom injection causes electroencephalographic and behavioral alterations ( Nencioni et al, 2009 ); fractions of this venom cause similar alterations and neuronal loss ( Lourenço et al, 2002 ); and some isolated toxins, when directly injected into the hippocampus of rats, induce wet dog shake (WDS), myoclonus, epileptic discharges ( Ossanai et al, 2012 ) and increase in the intracerebral level of glutamate ( Beraldo Neto et al, 2020 ).…”

“…The coordinates (AP −5.3, L −4.0, V −2.0.) were established according to the Stereotaxic Atlas of Paxinos and Watson (1998) and the surgical method was performed according to previous works ( Beraldo Neto et al, 2020 ; Nencioni et al, 2009 ; Ossanai et al, 2012 ).…”

“…As previously demonstrated, the fraction Tb II-I causes epileptic-like behavior, electrographic alterations such as grouped spikes and strong discharges, alters the level of some cytokines in the hippocampus, and additionally decreases the number of pyramidal cells in the CA1, CA3 and CA4 hippocampal areas ( Beraldo Neto et al, 2018 ). These effects are commonly associated with increase in the level of the glutamate, the main neurotransmitter associated with continued depolarization caused by scorpionic neuropeptides ( Beraldo Neto et al, 2020 ; Massensini et al, 1998 ; Nencioni et al, 2003 , 2009 ). However, in the present study we demonstrated an opposite effect, with no changes in the intrahippocampal level of glutamate and GABA.…”