High-Fat Diet Impairs Neural Function of APPswe /PS1ΔE9 Mice by Enhancing Inflammatory Response and Pyroptosis
10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0506
- VernacularTitle:高脂饮食诱导APPswe/PS1ΔE9小鼠脑内炎症反应及细胞焦亡损伤神经功能
- Author:
Ze LI
1
;
Zhen-yan SONG
1
;
Fu-zhou LI
1
;
Chun-xiang HE
1
;
Miao YANG
1
;
Wen-jing YU
1
;
Shao-wu CHENG
1
Author Information
1. Hunan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Cardio-Cerebral Diseases， Hunan University of Chinese Medicine，Changsha 410208，China
- Publication Type:Journal Article
- Keywords:
Alzheimer's disease;
high-fat diet;
obesity;
dementia;
microglia;
inflammation;
pyroptosis
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2021;42(5):686-693
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the relationship between chronic inflammatory response induced by high-fat diet （HFD） and neurological dysfunction in Alzheimer's disease. MethodsTwelve-month-old C57BL/6J and APPswe/PS1ΔE9 （APP/PS1） male mice were randomly divided into 4 groups according to body weight： control group （C57BL/6J mice on standard chow， n=6）， control on HFD group （C57BL/6J mice on HFD， n=6）， dementia group （APP/PS1 mice on standard chow， n=6） and dementia on HFD group （APP/PS1 mice on HFD， n=6）. The mice were fed with standard chow or HFD for 6 weeks. Changes in body weight of mice were monitored weekly. Immunohistochemistry was used to examine the activation of microglias in hippocampus. RT-qPCR was performed to detect the expression of inflammatory factors including IL-1β， IL-6 and TNF-α. Nissl staining was conducted to observe the morphology of neuronal Nissl bodies in hippocampal CA1 region. The expression levels of NLRP3 and caspase-1 in hippocampus were measured by Western blot. Neuronal pyroptosis in hippocampus was determined by TUNEL and caspase-1 immunofluorescence double staining. ResultsThe 2×2 factorial design analysis revealed that high-fat diet enhanced the activation of hippocampal microglias， elevated the mRNA levels of inflammatory factors （IL-1β， IL-6 and TNF-α） and the relative protein level of NLRP3 （P<0.05）， and decreased Nissl bodies in hippocampal CA1 region. APP/PS1 genes enhanced the activation of microglias and the expression of IL-1β， TNF-α， NLRP3 and caspase-1 in hippocampus （P<0.05）. High-fat diet interacted with APP/PS1 genes in microglia activation and IL-1β mRNA expression enhancement （P<0.05）. In dementia mice， high-fat diet enhanced the expression of caspase-1/TUNEL in the hippocampus （P<0.05）， aggravated the neuronal pyroptosis， and worsened the damage of Nissl bodies in hippocampal CA1 region. ConclusionHigh-fat diet and APP/PS1 genes both can enhance the inflammatory response in mouse brain. High-fat diet can further aggravate the pyroptosis and impairment of neural function in dementia mice.
