Abstract
Non-alcoholic fatty liver disease (NAFLD) leads to hippocampal damage and causes a variety of physiopathological responses, including the induction of endoplasmic reticulum stress (ERS), neuroinflammation, and alterations in synaptic plasticity. As an important trace element, strontium (Sr) has been reported to have antioxidant effects, to have anti-inflammatory effects, and to cause the inhibition of adipogenesis. The present study was undertaken to investigate the protective effects of Sr on hippocampal damage in NAFLD mice in order to elucidate the underlying mechanism of Sr in NAFLD. The mouse model of NAFLD was established by feeding mice a high-fat diet (HFD), and the mice were treated with Sr. In the NAFLD mice, we found that treatment with Sr significantly increased the density of c-Fos+ cells in the hippocampus and inhibited the expression of caspase-3 by suppressing ERS. Surprisingly, the induction of neuroinflammation and the increased expression of inflammatory cytokines in the hippocampus following an HFD were attenuated by Sr treatment. Sr significantly attenuated the activation of microglia and astrocytes induced by an HFD. The expression of phospho-p38, ERK, and NF-κB was consistently significantly increased in the HFD group, and treatment with Sr decreased their expression. Moreover, Sr prevented HFD-induced damage to the ultra-structural synaptic architecture. This study implies that Sr has beneficial effects on repairing the damage to the hippocampus induced by an HFD, revealing that Sr could be a potential candidate for protection from neural damage caused by NAFLD.