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

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.

Keywords: Astaxanthin; Blood–brain barrier; K+ channel blocker; Neurodegeneration; Neuroinflammatory response; Neurotoxin.