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.
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Availability of data and material
The data can not be shared because this is an ongoing study.
Code Availability
All analysis was performed by Statistical Product and Service Solutions 26.0.
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Acknowledgements
We wanted to thank Prof. Jia Qifen from TIANJIN UNIVERSITY (China) for the funding and laboratory support for this project.
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Zheng Chen, Lu Wang and Feng Wang conducted the study design, literature research and manuscript preparation. Guanghong Sui and Caixia Yang carried out the experiment and performed the data analysis. Guanghong Sui was responsible for the revision of the article.
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Chen, Z., Sui, G., Wang, L. et al. High-fat diet induced hippocampal CREB dysfunction, cognitive impairment and depression-like behaviors via downregulation of interleukin-2 in the mice. Metab Brain Dis 37, 1163–1174 (2022). https://doi.org/10.1007/s11011-022-00938-1
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DOI: https://doi.org/10.1007/s11011-022-00938-1