Role of Bmal1 in Type 2 Diabetes Mellitus-Related Glycolipid Metabolic Disorder and Neuropsychiatric Injury: Involved in the Regulation of Synaptic Plasticity and Circadian Rhythms

被引：6
|
作者：
Gao, Xinran [1 ,2 ,3 ]
Wei, Yadong [1 ,2 ,3 ]
Sun, Huaizhi [1 ,2 ,3 ]
Hao, Shengwei [1 ,2 ,3 ]
Ma, Mengdie [1 ,2 ,3 ]
Sun, Huimin [1 ,2 ,3 ]
Zang, Dandan [4 ]
Qi, Congcong [5 ]
Ge, Jinfang [1 ,2 ,3 ]
机构：
[1] Anhui Med Univ, Sch Pharm, 81 Meishan Rd, Hefei 230032, Anhui, Peoples R China
[2] Anhui Med Univ, Key Lab Antiinflammatory & Immune Med, Minist Educ, Hefei, Peoples R China
[3] Anhui Inst Innovat Drugs, Anhui Prov Lab Inflammatory & Immune Dis, Hefei, Peoples R China
[4] Anhui Med Univ, Ctr Sci Res, Hefei, Peoples R China
[5] Fudan Univ, Dept Lab Anim Sci, Shanghai, Peoples R China
来源：
MOLECULAR NEUROBIOLOGY | 2023年 / 60卷 / 08期
基金：
中国国家自然科学基金;
关键词：
T2DM; Bmal1; Glucolipid metabolism; Cognitive function; Circadian rhythms; Synaptic plasticity; DIET-INDUCED OBESITY; COGNITIVE DYSFUNCTION; GLUCOSE-HOMEOSTASIS; LOCOMOTOR-ACTIVITY; MELATONIN; IMPACT; BRAIN; DISRUPTION; ETIOLOGY; AGONIST;
D O I：
10.1007/s12035-023-03360-5
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Increasing data suggest a crucial role of circadian rhythm in regulating metabolic and neurological diseases, and Bmal1 is regarded as a key regulator of circadian transcription. The aim of this study is to investigate the role of Bmal1 in the disruption of circadian rhythm and neuropsychiatric injuries in type 2 diabetes mellitus (T2DM). A T2DM model was induced by the combination of high-fat-diet (HFD) and streptozotocin (STZ) in vivo or HT-22 cells challenged with palmitic-acid (PA) in vitro. The glucolipid metabolism indicators, behavioral performance, and expression of synaptic plasticity proteins and circadian rhythm-related proteins were detected. These changes were also observed after interference of Bmal1 expression via overexpressed plasmid or small interfering RNAs in vitro. The results showed that HFD/STZ could induce T2DM-like glycolipid metabolic turmoil and abnormal neuropsychiatric behaviors in mice, as indicated by the increased concentrations of fasting blood-glucose (FBG), HbA1c and lipids, the impaired glucose tolerance, and the decreased preference index of novel object or novel arm in the novel object recognition test (NOR) and Y-maze test (Y-maze). Consistently, the protein expression of synaptic plasticity proteins and circadian rhythm-related proteins and the positive fluorescence intensity of MT1B and Bmal1 were decreased in the hippocampus of HFD/STZ-induced mice or PA-challenged HT-22 cells. Furthermore, overexpression of Bmal1 could improve the PA-induced lipid metabolic dysfunction and increase the decreased expressions of synaptic plasticity proteins and circadian rhythm-related proteins, and vice versa. These results suggested a crucial role of Bmal1 in T2DM-related glycolipid metabolic disorder and neuropsychiatric injury, which mechanism might be involved in the regulation of synaptic plasticity and circadian rhythms.
引用
收藏
页码：4595 / 4617
页数：23
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