Neuromodulation of neurological disorders in a demyelination model: effect of a potassium channel inhibitor from Androctonus scorpion venom

Abstract

Scorpion’s toxins have attracted attention as a treatment for diverse neurological diseases related to myelin loss. This study aimed to investigate the effect of kaliotoxin2 (KTX2), a potassium-channel blocker from Androctonus australis hector venom on cuprizone model of demyelination. Results showed that KTX2 modulates the behavioral functions, the demyelination, and reduces the recruitment of microglia, astrocytes, and granulocyte in the brain. KTX2 modulates the inflammatory response by increasing the IL-10 release, attenuating NFκB activation, and decreasing the oxidative stress markers and IL-6 levels. Results highlight the modulating effects of KTX2 on cuprizone model and confirm its therapeutic potential in demyelination diseases.

Highlights

• Kaliotoxin2 (KTX2) prevents the excessive reduction in body weight gain and modulate motor coordination disorder induced by cuprizone.

• KTX2 from Aah venom protect myelin from the destructive effects of cuprizone.

• KTX2 inoculation to the CNS reduce microglia, astrocytes and granulocyte infiltration in the brain.

• KTX2 increases the production of the anti-inflammatory cytokine IL-10 and attenuates the activation of NFκB.

• KTX2 counterbalances cuprizone-induced brain unbalance of neurochemical redox parameters.

Keywords:

• Demyelination
• kaliotoxin2
• potassium channels
• neuroinflammation
• neurobehavioral functions
• neuromodulation

Acknowledgments

The authors thank Professor Marie France Martin-Eauclaire (Laboratory of Cognitive Neuroscience, CNRS, Aix Marseille Univ, UMR 7291, 13003 Marseille, France) for kindly providing us with the purified KTX2.

Disclosure statement

Authors confirm that there is no conflict of interest associated with this publication. H.M., A.L-M., and F.L-D designed of experiment; H.M. performed the experiments; H.M., A.L.-M., and F.L.-D analyzed the data; H.M., A.L.-M., and F.L.-D wrote the manuscript. All authors have read and agreed the submitted version of the manuscript.

Data availability statement

Our data implicate that KTX2 such as CBD is able to attenuate destructive cuprizone effects in the brain by decreasing oxidative stress and reducing microglia accumulation.

Additional information

Funding

This research received no external funding.