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K+ channel blocker-induced neuroinflammatory response and neurological disorders: immunomodulatory effects of astaxanthin

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Abstract

Objective

Channelopathies due to the brain ion channel dysfunction is considered to be an important mechanism involved in various neurodegenerative diseases. In this study, we evaluated the ability of kaliotoxin (KTX) as K+ channel blocker to induce neuro-inflammatory response and neurodegenerative alteration. We also investigate the effects of astaxanthin (ATX) against KTX disorders.

Material and treatment

NMRI mice were injected with KTX (1 pg/kg, by i.c.v route) with or without pretreatment using ATX (80 mg/kg, o.p route).

Results

Results showed that KTX was detected in cerebral cortex area due to its binding to the specific receptors (immunofluorescence analysis). It induced an activation of inflammatory cascade characterized by an increase of IL-6, TNFα, NO, MDA levels and NF-κB expression associated to a decrease of GSH level. The neuroinflammatory response is accompanied with cerebral alterations and blood–brain barrier (BBB) disruption. The use of ATX prior to the KTX exerts a preventive effect not only on the neuroinflammation but also on altered tissues and the BBB disruption.

Conclusions

Kaliotoxin is able to induce neurological disorders by blocking the K+ ion channel, and ATX suppresses this alterations with down regulation of IL-6, TNF-α and NF-κB expression in the brain.

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Authors and Affiliations

  1. USTHB, Faculty of Biological Sciences, Laboratory of Cellular and Molecular Biology, BP32, El Alia, Bab Ezzouar, 16111, Algiers, Algeria

    Nesrine Sifi & Fatima Laraba-Djebari

  2. CRN2M UMR 7286, CNRS, Aix Marseille Université, 13344, Marseille Cedex 15, France

    Marie-France Martin-Eauclaire

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  1. Nesrine Sifi
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  2. Marie-France Martin-Eauclaire
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  3. Fatima Laraba-Djebari
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Correspondence to Fatima Laraba-Djebari.

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Sifi, N., Martin-Eauclaire, MF. & Laraba-Djebari, F. K+ channel blocker-induced neuroinflammatory response and neurological disorders: immunomodulatory effects of astaxanthin. Inflamm. Res. 65, 623–634 (2016). https://doi.org/10.1007/s00011-016-0945-y

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  • DOI: https://doi.org/10.1007/s00011-016-0945-y

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