Effects of liraglutide on
inflammation and mitochondrial fusion/division in Parkinson’s disease model of mice induced by paraquat

LIU Zhe-Chuan; LI Kun; MA Shuai-Nan; MENG Jia-Qi; WANG Yan-Qin

doi:10.16098/j.issn.0529-1356.2023.06.008

PDF(1766 KB)

Acta Anatomica Sinica ›› 2023, Vol. 54 ›› Issue (6) : 676-681. DOI: 10.16098/j.issn.0529-1356.2023.06.008

Effects of liraglutide on inflammation and mitochondrial fusion/division in Parkinson’s disease model of mice induced by paraquat

LIU Zhe-chuan LI Kun MA Shuai-nan MENG Jia-qi WANG Yan-qin*

Author information +

History +

Abstract

Objective To investigate the protective effect and mechanism of liraglutide on the paraquat (PQ)-induced Parkinson’s disease (PD) mouse model. Methods Totally 24 Kunming mice were randomly divided into control group, PQ group and PQ +liraglutide group, 8 mice in each group. PD model was established by intraperitoneal injection of PQ (10 mg/kg) for 5 consecutive days, and liraglutide (50 nmol/kg) was injected intraperitoneally for 7 consecutive days. The free-standing and locomotor activity of mice were measured by behavioral method. Immunofluorescence was used to observe the number of tyrosine hydroxylase (TH) and ionized calcium binding adaptor molecule 1 (Iba1) immunoreactive cells. Western blotting was used to detect the expression of protein TH, glial fibrillary acidic protein (GFAP), mitofusin-2 (Mfn2) and dynamin-related protein 1 (Drp1). Results The numbers of free-standing and locomotor activity numbers decreased significantly (P<0.01, P<0.05) in PQ group compared with the control group, and the number of TH immunoreactive cells and TH protein expression in substantia nigra decreased significantly (P<0.01, P<0.01) compared with the control group, while the number of Iba1 immunoreactive cells and GFAP protein expression increased significantly (P<0.01, P<0.01) compared with the control group; the expression of Drp1 protein in PQ group was significantly higher than that in control group (P<0.05), while the Mfn2 protein expression decreased significantly (P<0.05) compared with the control group. After treatment with liraglutide, the number of TH positive cells in PQ + liraglutide group was significantly lower than that in control group (P<0.05); the numbers of free-standing and locomotor activity increased significantly (P<0.05, P<0.05) in PQ + liraglutide group compared with the PQ group, and the number of TH positive cells and expression of TH protein in PQ + liraglutide group were significantly higher than that in PQ group (P<0.01, P<0.01); while the number of Iba1 positive cells and GFAP protein expression decreased significantly (P<0.01, P<0.05) compared with the PQ group; the Drp1 protein expression decreased significantly (P<0.01) compared with the PQ group, while the expression of Mfn2 protein in PQ + liraglutide group was significantly higher than that in PQ group (P<0.01). Conclusion Liraglutide has neuroprotective effect by reducing neuroinflammation in substantia nigra, regulating mitochondrial fusion and fission.

Key words

Parkinson’s disease / Liraglutide / Paraquat / Inflammation / Mitochondrial fusion/division / Immunofluorescence / Western blotting / Mouse

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

LIU Zhe-chuan LI Kun MA Shuai-nan MENG Jia-qi WANG Yan-qin. Effects of liraglutide on inflammation and mitochondrial fusion/division in Parkinson’s disease model of mice induced by paraquat[J]. Acta Anatomica Sinica. 2023, 54(6): 676-681 https://doi.org/10.16098/j.issn.0529-1356.2023.06.008

References

［1］Tysnes OB, Storstein A. Epidemiology of Parkinson’s disease ［J］. J Neural Transm (Vienna), 2017,124(8):901-905.

［2］Beitz JM. Parkinson’ disease: a review［J］. Front Biosci (Schol Ed), 2014, (1):65-74.

［3］Sun X, Liang JQ, He JCh, et al. Research progress of animal models of Parkinson’s disease induced by neurotoxin［J］. Journal of Medical Research, 2020, 49(12):21-24.（in Chinese）

孙雪, 梁建庆, 何建成, 等. 神经毒素诱导帕金森病动物模型的研究进展［J］. 医学研究杂志, 2020, 49(12):21-24.

［4］Wang TT, Chen ZhCh, Ye X, et al. Effect of allopregnenolone on the dopaminergic neurons in the substantia nigra of Parkinson’s disease mice［J］. Acta Anatomisica Sinica, 2020, 51(4):473-482.（in Chinese）

王彤彤, 陈治池, 叶鑫, 等. 别孕烯醇酮对帕金森病模型小鼠黑质多巴胺能神经元的影响及可能的分子机制［J］. 解剖学报, 2020, 51(4):473-482.

［5］Marogianni C, Sokratous M, Dardiotis E, et al. Neurodegeneration and inflammation-an interesting interplay in Parkinson’s disease［J］. Int J Mol Sci, 2020,21(22):8427.

［6］Bose A, Beal MF. Mitochondrial dysfunction in Parkinson’s disease［J］. J Neurochem, 2016,139(1):216-231.

［7］Zhang L, Zhang L, Li Y, et al. The novel dual GLP-1/GIP receptor agonist DA-CH5 is superior to single GLP-1 receptor agonists in the MPTP model of Parkinson’s disease［J］. J Parkinsons Dis, 2020,10(2):523-542.

［8］Lin TK, Lin KJ, Lin HY, et al. Glucagon-like peptide-1 receptor agonist ameliorates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity through enhancing mitophagy flux and reducing α-synuclein and oxidative stress［J］. Front Mol Neurosci, 2021,14:697440.

［9］Jalewa J, Sharma MK, Hlscher C. Novel incretin analogues improve autophagy and protect from mitochondrial stress induced by rotenone in SH-SY5Y cells［J］. J Neurochem, 2016,139(1):55-67.

［10］Williams GP, Schonhoff AM, Jurkuvenaite A, et al. CD4 T cells mediate brain inflammation and neurodegeneration in a mouse model of Parkinson’s disease［J］. Brain, 2021,144(7):2047-2059.

［11］Hickman S, Izzy S, Sen P, et al. Microglia in neurodegeneration［J］. Nat Neurosci, 2018,21(10):1359-1369.

［12］Siracusa R, Fusco R, Cuzzocrea S. Astrocytes: role and functions in brain pathologies［J］. Front Pharmacol, 2019,10:1114.

［13］Diao X, Wang F, Becerra-Calixto A, et al. Induced pluripotent stem cell-derived dopaminergic neurons from familial Parkinson’s disease patients display α-synuclein pathology and abnormal mitochondrial morphology［J］. Cells, 2021,10(9):2402.

［14］Cao B, Zhang Y, Chen J, et al. Neuroprotective effects of liraglutide against inflammation through the AMPK/NF-κB pathway in a mouse model of Parkinson’s disease［J］. Metab Brain Dis, 2022,37(2):451-462.

［15］Monzio Compagnoni G, Di Fonzo A, Corti S, et al. The role of mitochondria in neurodegenerative diseases: the lesson from Alzheimer’s disease and Parkinson’s disease［J］. Mol Neurobiol, 2020,57(7):2959-2980.

［16］Richter V, Singh AP, Kvansakul M, et al. Splitting up the powerhouse: structural insights into the mechanism of mitochondrial fission［J］. Cell Mol Life Sci, 2015,72(19):3695-3707.

［17］Feng ST, Wang ZZ, Yuan YH, et al. Dynaminrelated protein 1: a protein critical for mitochondrial fission, mitophagy, and neuronal death in Parkinson’s disease［J］. Pharmacol Res, 2020,151:104553.

［18］Lee JY, Nagano Y, Taylor JP, et al. Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy［J］. J Cell Biol, 2010,189(4):671-679.

［19］Pham AH, Meng S, Chu QN, et al. Loss of Mfn2 results in progressive, retrograde degeneration of dopaminergic neurons in the nigrostriatal circuit［J］. Hum Mol Genet, 2012,21(22):4817-4826.

［20］Zhao F, Wang W, Wang C, et al. Mfn2 protects dopaminergic neurons exposed to paraquat both in vitro and in vivo: implications for idiopathic Parkinson’s disease［J］. Biochim Biophys Acta Mol Basis Dis, 2017,1863(6):1359-1370.

［21］Hu Z, Mao C, Wang H, et al. CHIP protects against MPP(+)/MPTP-induced damage by regulating Drp1 in two models of Parkinson’s disease［J］. Aging (Albany NY), 2021,13(1):1458-1472.

［22］Wu P, Dong Y, Chen J, et al. Liraglutide regulates mitochondrial quality control system through PGC-1α in a mouse model of Parkinson’s disease［J］. Neurotox Res, 2022,40(1):286-297.

［23］Jassim AH, Inman DM, Mitchell CH. Crosstalk between dysfunctional mitochondria and inflammation in glaucomatous neurodegeneration［J］. Front Pharmacol, 2021,12:699623.

［24］Voloboueva LA, Emery JF, Sun X, et al. Inflammatory response of microglial BV-2 cells includes a glycolytic shift and is modulated by mitochondrial glucose-regulated protein 75/mortalin［J］. FEBS Lett, 2013,587(6):756-762.

［25］Misawa T, Takahama M, Kozaki T, et al. Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome［J］. Nat Immunol, 2013,14(5):454-460.

［26］Ongnok B, Maneechote C, Chunchai T, et al. Modulation of mitochondrial dynamics rescues cognitive function in rats with ’doxorubicin-induced chemobrain via ’ mitigation of mitochondrial dysfunction and neuroinflammation［J］. FEBS J, 2022,289(20):6435-6455.

［27］Stavropoulos F, Sargiannidou I, Potamiti L, et al. Aberrant mitochondrial dynamics and exacerbated response to neuroinflammation in a novel mouse model of CMT2A［J］. Int J Mol Sci, 2021,22(21):11569.