High-fat diet induced hippocampal CREB dysfunction, cognitive impairment and depression-like behaviors via downregulation of interleukin-2 in the mice.

Background: Inhibition of hippocampal CREB signaling contributed to obesity-induced cognitive impairment. But, the potential mechanism by which obesity inhibits hippocampal CREB signaling is not clear. The aim of this study was to explore whether interleukin-2 played a intermediary role in this pathogenic effect in a high-fat diet model.

Methods: C57BL/6J interleukin-2 wild-type and interleukin-2 knockout mice were fed a standard diet or high-fat diet for 12 weeks. After that, cognitive function was assessed by Morris water maze and Y maze. Depression-like behaviors were determined using sucrose preference test and tail suspension test. Expression of p-CREB and interleukin-2 in peripheral blood mononuclear cells and hippocampus was measured using western blotting and qRT-PCR.

Results: In the interleukin-2 wild-type mice, a high-fat diet inhibited the expression of interleukin-2 and p-CREB both in the peripheral blood mononuclear cells and hippocampus. The high-fat diet also caused cognitive impairment and depression-like behaviors in these mice. In the interleukin-2 knockout mice, there was no significant depression of interleukin-2. A high-fat diet can only aggravate the p-CREB signaling dysfunction in the peripheral blood mononuclear cells, but not in the hippocampus. Meanwhile, the high-fat diet can not cause the cognitive impairment and depression-like behaviors in these mice.

Conclusions: A high-fat diet induced hippocampal CREB dysfunction, cognitive impairment and depression-like behaviors partly through downregulation of interleukin-2 in the mice.