PMID- 37126129 OWN - NLM STAT- MEDLINE DCOM- 20230628 LR - 20231213 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 60 IP - 8 DP - 2023 Aug TI - 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. PG - 4595-4617 LID - 10.1007/s12035-023-03360-5 [doi] AB - 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. CI - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Gao, Xinran AU - Gao X AD - School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China. AD - The Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China. AD - Anhui Provincial Laboratory of Inflammatory and Immune Disease, Anhui Institute of Innovative Drugs, Hefei, China. FAU - Wei, Yadong AU - Wei Y AD - School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China. AD - The Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China. AD - Anhui Provincial Laboratory of Inflammatory and Immune Disease, Anhui Institute of Innovative Drugs, Hefei, China. FAU - Sun, Huaizhi AU - Sun H AD - School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China. AD - The Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China. AD - Anhui Provincial Laboratory of Inflammatory and Immune Disease, Anhui Institute of Innovative Drugs, Hefei, China. FAU - Hao, Shengwei AU - Hao S AD - School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China. AD - The Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China. AD - Anhui Provincial Laboratory of Inflammatory and Immune Disease, Anhui Institute of Innovative Drugs, Hefei, China. FAU - Ma, Mengdie AU - Ma M AD - School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China. AD - The Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China. AD - Anhui Provincial Laboratory of Inflammatory and Immune Disease, Anhui Institute of Innovative Drugs, Hefei, China. FAU - Sun, Huimin AU - Sun H AD - School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China. AD - The Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China. AD - Anhui Provincial Laboratory of Inflammatory and Immune Disease, Anhui Institute of Innovative Drugs, Hefei, China. FAU - Zang, Dandan AU - Zang D AD - The Center for Scientific Research of Anhui Medical University, Hefei, China. FAU - Qi, Congcong AU - Qi C AD - Department of Laboratory Animal Science, Fudan University, Shanghai, China. FAU - Ge, Jinfang AU - Ge J AUID- ORCID: 0000-0002-6289-9934 AD - School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China. gejinfang@ahmu.edu.cn. AD - The Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China. gejinfang@ahmu.edu.cn. AD - Anhui Provincial Laboratory of Inflammatory and Immune Disease, Anhui Institute of Innovative Drugs, Hefei, China. gejinfang@ahmu.edu.cn. LA - eng GR - 81870403/National Natural Science Foundation of China/ GR - gxbjZD2022013/Foundation for the Top Talents in university of Anhui Province/ GR - 2022xkjT009/Scientific Research Promotion Plan of Anhui Medical University/ PT - Journal Article DEP - 20230501 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (ARNTL Transcription Factors) RN - 0 (Bmal1 protein, mouse) SB - IM MH - Animals MH - Mice MH - ARNTL Transcription Factors/genetics MH - Circadian Rhythm/physiology MH - *Diabetes Mellitus, Type 2/complications/metabolism OTO - NOTNLM OT - Bmal1 OT - Circadian rhythms OT - Cognitive function OT - Glucolipid metabolism OT - Synaptic plasticity OT - T2DM EDAT- 2023/05/01 12:44 MHDA- 2023/06/28 06:42 CRDT- 2023/05/01 11:05 PHST- 2023/02/20 00:00 [received] PHST- 2023/04/19 00:00 [accepted] PHST- 2023/06/28 06:42 [medline] PHST- 2023/05/01 12:44 [pubmed] PHST- 2023/05/01 11:05 [entrez] AID - 10.1007/s12035-023-03360-5 [pii] AID - 10.1007/s12035-023-03360-5 [doi] PST - ppublish SO - Mol Neurobiol. 2023 Aug;60(8):4595-4617. doi: 10.1007/s12035-023-03360-5. Epub 2023 May 1.