Intrahippocampal injection of TsTX-I increases the levels of INF-γ in the cerebral tissue but not the levels of glutamate

Rodriguez, Renan Volner; Dorce, Valquíria Abrão Coronado; Freitas, Lucas Alves de; Dorce, Ana Leticia Coronado; Lebrun, Ivo; Sobral, Ana Claudia Martins; Portaro, Fernanda Calheta Vieira; Kuniyoshi, Alexandre Kazuo; Cajado-Carvalho, Daniela; Nencioni, Ana Leonor Abrahão

doi:10.1016/j.toxicon.2015.07.006

Cited by 5 publications

(9 citation statements)

References 27 publications

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“…Similarly, the intracerebral injection of Tb1 in rats causes epileptic-like discharges, but apparently, it is more toxic, since it caused an intense neuronal damage and increase in the level of hippocampal glutamate. However, the dose used in this study (2.0 µg, the group's standard when performing pharmacological characterization) was higher than those used by Teixeira [42] and Rodriguez [43] (0.005 and 0.125 µg, respectively). Such a difference could explain the more intense observed effects.…”

Section: Discussionmentioning

confidence: 72%

“…Some of these toxins have been investigated regarding the systemic effects and the interaction on sodium channels [34][35][36][37][38]. On the other hand, the central effects were evaluated only with Ts1 [41][42][43] and Tb1 in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…When intracerebrally injected in rats, it causes epileptiform discharges, paralysis in hind limbs, and respiratory distress, followed by death at higher doses [42]. Moreover, Ts1 alters cytokine levels without damaging neurons or altering the hippocampal concentration of glutamate [43]. Similarly, the intracerebral injection of Tb1 in rats causes epileptic-like discharges, but apparently, it is more toxic, since it caused an intense neuronal damage and increase in the level of hippocampal glutamate.…”

Section: Discussionmentioning

confidence: 99%

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

Beraldo-Neto

Freitas

Pimenta

et al. 2020

Toxins

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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.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Beraldo-Neto

Freitas

Pimenta

et al. 2020

Toxins

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“…Additionally, Ts1 inhibits the sodium current through Nav 1.5 channels without altering the activation or steady-state inactivation curves [ 76 ]. The intracerebral injection of Ts1 in rats causes epileptiform discharges and wet dog shake behavior, and it is also able to cause paralysis of the hind limbs and severe respiratory distress followed by death [ 46 ], without altering the intrahippocampal concentration of glutamate [ 77 ]. The injection of Ts1 affects the neuroimmunological system, increasing the level of tumor necrosis factor α (TNF-α) and interferon gamma (IFN-γ) in the rat brain [ 77 , 78 ].…”

Section: Introductionmentioning

confidence: 99%

“…The intracerebral injection of Ts1 in rats causes epileptiform discharges and wet dog shake behavior, and it is also able to cause paralysis of the hind limbs and severe respiratory distress followed by death [ 46 ], without altering the intrahippocampal concentration of glutamate [ 77 ]. The injection of Ts1 affects the neuroimmunological system, increasing the level of tumor necrosis factor α (TNF-α) and interferon gamma (IFN-γ) in the rat brain [ 77 , 78 ]. Ts3, also known as TsTX, toxin IV-5, TS-8F or tityustoxin, is considered the most lethal α-toxin, component of the T. serrulatus venom [ 79 , 80 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Brazilian scorpion venoms on the central nervous system

Nencioni

Beraldo-Neto

Freitas

et al. 2018

J Venom Anim Toxins Incl Trop Dis

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In Brazil, the scorpion species responsible for most severe incidents belong to the Tityus genus and, among this group, T. serrulatus, T. bahiensis, T. stigmurus and T. obscurus are the most dangerous ones. Other species such as T. metuendus, T. silvestres, T. brazilae, T. confluens, T. costatus, T. fasciolatus and T. neglectus are also found in the country, but the incidence and severity of accidents caused by them are lower. The main effects caused by scorpion venoms – such as myocardial damage, cardiac arrhythmias, pulmonary edema and shock – are mainly due to the release of mediators from the autonomic nervous system. On the other hand, some evidence show the participation of the central nervous system and inflammatory response in the process. The participation of the central nervous system in envenoming has always been questioned. Some authors claim that the central effects would be a consequence of peripheral stimulation and would be the result, not the cause, of the envenoming process. Because, they say, at least in adult individuals, the venom would be unable to cross the blood-brain barrier. In contrast, there is some evidence showing the direct participation of the central nervous system in the envenoming process. This review summarizes the major findings on the effects of Brazilian scorpion venoms on the central nervous system, both clinically and experimentally. Most of the studies have been performed with T. serrulatus and T. bahiensis. Little information is available regarding the other Brazilian Tityus species.

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Cyclooxygenase-2 inhibitors differentially attenuate pentylenetetrazol-induced seizures and increase of pro- and anti-inflammatory cytokine levels in the cerebral cortex and hippocampus of mice

Temp

Marafiga

Milanesi

et al. 2017

European Journal of Pharmacology

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Seizures increase prostaglandin and cytokine levels in the brain. However, it remains to be determined whether cyclooxygenase-2 (COX-2) derived metabolites play a role in seizure-induced cytokine increase in the brain and whether anticonvulsant activity is shared by all COX-2 inhibitors. In this study we investigated whether three different COX-2 inhibitors alter pentylenetetrazol (PTZ)-induced seizures and increase of interleukin-1β (IL-1β), interleukin-6 (IL-6), interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) levels in the hippocampus and cerebral cortex of mice. Adult male albino Swiss mice received nimesulide, celecoxib or etoricoxib (0.2, 2 or 20mg/kg in 0.1% carboxymethylcellulose (CMC) in 5% Tween 80, p.o.). Sixty minutes thereafter the animals were injected with PTZ (50mg/kg, i.p.) and the latency to myoclonic jerks and to generalized tonic-clonic seizures were recorded. Twenty minutes after PTZ injection animals were killed and cytokine levels were measured. PTZ increased cytokine levels in the cerebral cortex and hippocampus. While celecoxib and nimesulide attenuated PTZ -induced increase of proinflammatory cytokines in the cerebral cortex, etoricoxib did not. Nimesulide was the only COX-2 inhibitors that attenuated PTZ-induced seizures. This effect coincided with an increase of IL-10 levels in the cerebral cortex and hippocampus, constituting circumstantial evidence that IL-10 increase may be involved in the anticonvulsant effect of nimesulide.

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Intrahippocampal injection of TsTX-I increases the levels of INF-γ in the cerebral tissue but not the levels of glutamate

Cited by 5 publications

References 27 publications

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

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

Effects of Brazilian scorpion venoms on the central nervous system

Cyclooxygenase-2 inhibitors differentially attenuate pentylenetetrazol-induced seizures and increase of pro- and anti-inflammatory cytokine levels in the cerebral cortex and hippocampus of mice

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