Docosahexaenoic acid may act as a neuroprotector for methylmercury-induced neurotoxicity in primary neural cell cultures

The ability of docosahexaenoic acid (DNA) to modulate methylmercury (MeHg)-induced neurotoxicity was investigated in primary astrocytes and neurons from the cerebellum. Gas chromatography measurements indicated increased DHA content in both cell types after 24 h supplementation. After individual or combined treatment with MeHg (10 mu M) and DHA (30 and 90 mu M), the cell-associated MeHg measurements were done using C-14-labelled MeHg. In addition, mitochondrial activity was evaluated by MTT reduction, glutathione (GSH) content was measured with the fluorescent indicator monochlorobimane (MCB) and reactive oxygen species (ROS) were detected with the fluorescent indicator-chloro methyl derivative of di-chloro di-hydro fluorescein diacetate (CMH(2)DCFDA). For all the tested treatments, i.e. DNA, MeHg or DHA+MeHg treatment, the neurons differed significantly (p < 0.001) from astrocytes exhibiting increased ROS production and decreased MTT activity. After MeHg and 30 mu M DHA treatment there were no changes in MTT or GSH content but significant decrease (p < 0.001) in ROS was observed in both the cell types when compared to MeHg alone. The cell-associated MeHg measurements indicated reduced MeHg-accumulation in both cell types (p < 0.05) upon 30 mu M DHA exposure. Taken together, this study, for the first time establishes that DHA pretreatment effectively reduces cell-associated MeHg and prooxidant response from MeHg in both cerebellar astrocytes and neurons and thus supports the hypothesis that fish-derived nutrients offer possible neuroprotection from MeHg. (c) 2008 Elsevier Inc. All rights reserved.