Zheng Chen1, Guanghong Sui2, Lu Wang3, Caixia Yang4, Feng Wang5,6. 1. Department of Psychology, Tianjin Anding Hospital, 300074, Tianjin, China. Zheng4365@126.com. 2. Department of Child and Adolescent Psychology, Tianjin Anding Hospital, 300074, Tianjin, China. 3. Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, 300052, Tianjin, China. 4. Department of Rehabilitation, Tianjin Anding Hospital, 300074, Tianjin, China. 5. Department of Psychology, Tianjin Anding Hospital, 300074, Tianjin, China. wangfeng0921@126.com. 6. Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, 300052, Tianjin, China. wangfeng0921@126.com.
Abstract
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.
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.