Molecular mechanisms of aluminium ions neurotoxicity in brain cells of fish from various pelagic areas

Abstract

Neurotoxic effects of aluminum chloride in higher than usual environment concentration (10 mg/L) were studied in brains of fishes from various pelagic areas, especially in sunfish (Lepomis macrochirus Rafinesque, 1819), roach (Rutilus rutilus Linnaeus, 1758), crucian carp (Carasius carasius Linnaeus, 1758), goby (Neogobius fluviatilis Pallas, 1811). The intensity of oxidative stress and the content of both cytoskeleton protein GFAP and cytosol Ca-binding protein S100 beta were determined. The differences in oxidative stress data were observed in the liver and brain of fish during 45 days of treatment with aluminum chloride. The data indicated that in the modeling of aluminum intoxication in mature adult fishes the level of oxidative stress was noticeably higher in the brain than in the liver. This index was lower by1.5-2.0 times on average in the liver cells than in the brain. The obtained data evidently demonstrate high sensitivity to aluminum ions in neural tissue cells of fish from various pelagic areas. Chronic intoxication with aluminum ions induced intense astrogliosis in the fish brain. Astrogliosis was determined as result of overexpression of both cytoskeleton and cytosole markers of astrocytes -GFAP and protein S100 beta (on 75-112\% and 67-105\% accordingly). Moreover, it was shown that the neurotixic effect of aluminum ions is closely related to metabolism of astroglial intermediate filaments. The results of western blotting showed a considerable increase in the content of the lysis protein products of GFAP with a range of molecular weight from 40-49 kDa. A similar metabolic disturbance was determined for the upregulation protein S100 beta expression and particularly in the increase in the content of polypeptide fragments of this protein with molecular weight 24-37 kDa. Thus, the obtained results allow one to presume that aluminum ions activate in the fish brain intracellular proteases which have a capacity to destroy the proteins of intermediate filaments. The data presented display the pronounced neurotoxic effect of mobile forms of aluminum on both expression level and the metabolism of molecular markers of astrocytes GFAP and protein S100 beta. Aluminum ions induce integrated changes, the more important of which are a significant increase in final LPO products, an increase in antioxidant enzyme activity, a reactivation of glial cells in the brain. Integrated determination of the content and polypeptide fragments of specific astrocyte proteins in fishes brains coupled with oxidative stress data may be used as valid biomarkers of toxic pollutant effects in aquatic environments.