Insulin-like growth factor-1 (IGF-1) improves cognitive function, but its mechanism has not been elucidated. The aim of the study was to explore whether IGF-1 exerted its protective effect on cognitive function and anxiety behavior through activation of PI3K/Akt/CREB pathway in high-fat diet rats. Neuronal cells HT22 were treated with nothing, IGF-1, IGF-1+LY294002 or IGF-1+666-15. Expressions of p-PI3K, p-Akt and p-CREB were measured using western blot analysis. Thirty C57BL/6J rats were used.

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... After feeding with high-fat diet, normal saline, PEG-IGF-1, PEG-IGF-1+LY294002 or PEG-IGF-1+666-15 was treated. Cognitive function and anxiety behavior were assessed by Morris water maze and open field test. Several inflammation and oxidative stress biomarkers were measured using recognized methods. Expressions of p-PI3K and p-CREB were also measured using western blot analysis. After IGF-1 treatment in cells, expressions of p-PI3K, p-Akt and p-CREB were increased. Furthermore, LY294002 down-regulated the expressions of these three proteins, but 666-15 only inhibited the expression of CREB in the cells. Compared with the control rats, we found abnormalities of cognitive function and anxiety behavior, inhibition of PI3K/Akt/CREB pathway and increase of oxidative stress and inflammation in high-fat diet rats. After PEG-IGF-1 treatment, the changes in high-fat diet rats were reversed. Then, we blocked the pathway and found that these blockers attenuated the protective effects of PEG-IGF-1. In conclusion, IGF-1 improved cognitive function and anxiety behavior in high-fat diet rats and inhibited inflammation and oxidative stress in hippocampus tissue through activation of PI3K/Akt/CREB pathway.