Long-term atorvastatin improves cognitive decline by regulating gut function in naturally ageing rats
Tian‐Ce Xu, Yan Lv, Quanying Liu, Dawei Chen
Abstract
Abstract Background Statins have been widely used to prevent cardiovascular disease in middle-aged and elderly populations; however, the effect of long-term treatment on cognitive function is controversial. To simulate clinical conditions, middle-aged rats were given atorvastatin for 9 consecutive months to investigate the effect on natural cognitive decline and the possible mechanisms. Results The results showed that compared with the control group, long-term atorvastatin treatment naturally improved cognitive decline. Furthermore, long-term treatment regulated intestinal retinoic acid (RA) metabolism and storage by altering retinol dehydrogenase 7 (Rdh7) expression in the intestine, while RA metabolism affected the proliferation of intestinal T reg cells and inhibited IL-17 + γδ T-cell function. In addition, long-term atorvastatin increased intestinal flora richness and decreased IL-17 expression in hippocampal tissue. Conclusion Collectively, these findings provide the first evidence that long-term atorvastatin intervention may prevent cognitive decline in naturally ageing rats by inhibiting neuroinflammation via the gut-brain axis.