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.

Highlights

  • Sodium channels play an essential role by establishing cell excitability and maintaining the conductance of excitable cells [1]

  • Tb1 was obtained by C18-RP-high-performance liquid chromatography (HPLC), according to Beraldo-Neto [12], from Fraction II of the Sephadex G25 size exclusion chromatography of T. bahiensis venom, which was previously termed TbII-II

  • A trypsin- digested proteomic approach was performed, and the results were analyzed against a transcriptome database obtained from the venom gland of T. bahiensis

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Summary

Introduction

Sodium channels play an essential role by establishing cell excitability and maintaining the conductance of excitable cells [1]. Several nervous system diseases may be correlated to them [1], such as epilepsy, pain, brain tumors, neural trauma, and multiple sclerosis [2]. Epilepsy is a quite common neurological syndrome [3] characterized by the occurrence of recurrent, unprovoked seizures [4] that are in part explained by an imbalance between excitatory and inhibitory conductance in the brain [5]. Despite the large availability of antiepileptic drugs (AED), there are a percentage of treatment-resistant individuals [6,7]. AED often may exert strong side effects [8]. There is a clear need to develop new drugs to aid such patients by improving their quality of life

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