High-fat diets impair spatial learning of mice in the Y-maze paradigm: ameliorative potential of α-lipoic acid.

High-fat diets (HFDs) have been found to influence central nervous system development and to cause cognitive impairments in human epidemiologic studies, as well as in animal investigations. These adverse effects on learning and memory induced by an HFD have been associated with an impaired hippocampus, including hippocampal oxidative damage. Previously, we had found that α-lipoic acid (α-LA) could ameliorate the oxidative stress in non-neural organs (liver, jejunum, and spleen) induced by a 10-week HFD (21.2% fat) food regimen in mice. In this study, we investigated whether a 10-week HFD (21.2% fat) induced oxidative stress in the hippocampus or impaired spatial learning in mice and whether LA ameliorated these effects. The HFD was found to induce oxidative stress (a decrease in catalase activity, glutathione peroxidase activity, and total antioxidative capacity and an increase in malondialdehyde levels) in the mouse hippocampus. In addition, we found that the HFD impaired spatial recognition memory of mice in the Y-maze paradigm. Furthermore, the hippocampal oxidative stress and impaired spatial recognition memory of the mice were reduced in HFD diets supplemented with 0.1% LA. These findings suggest that LA, as a strong antioxidant, may help prevent HFD-induced learning impairments by ameliorating associated oxidative stress in the hippocampus.