Effects of Voluntary Wheel Running Exercise on Learning and Memory Function of Young Mice and Related Mechanisms
DOI: 10.23977/medcm.2021.030230 | Downloads: 1 | Views: 308
Sun Wei 1, WU Qiao 1
1 Department of Psychiatry, the Third People's Hospital of Mianyang, Mianyang, Sichuan, 621000, China
Corresponding AuthorWU Qiao
Objective: This study is to investigate the effects of appropriate exercise on learning and memory function of mice, and the related mechanisms involving PAI-1 and miRNA (miR)-30b. Methods: Mice were subjected to the voluntary wheel running exercise training for 8 m. Morris water maze test was performed to assess the animal learning and memory function. Quantitative real-time PCR was conducted to detect the mRNA expression levels, while Western blot analysis and ELISA were used to determine protein expression levels. Bioinformatics analysis and dual-luciferase reporter assay were used to predict and confirm the up-stream regulator of PAI-1. Results: Morris water maze test showed that, compared with the control group, the escape latency was significantly declined in the exercise group. The swimming distance was significantly declined, while the platform crossing number was significantly increased, in the exercise group. Quantitative real-time PCR and Western blot analysis showed that, compared with the control group, the mRNA and protein expression levels of PAI-1 in both the hippocampal and blood tissues were significantly declined in the exercise group. According to the bioinformatics analysis, miR-30b might be the up-stream regulator of PAI-1, which was confirmed by the dual-luciferase reporter assay. In addition, compared with the control group, the expression levels of miR-30b in both the hippocampal and blood tissue samples were significantly elevated for the exercise group. Conclusion: Appropriate amount of exercise could improve the mouse learning and memory function, which might involve the up-regulated miR-30b expression and down-regulated PAI-1 expression in the hippocampal and blood tissues.
KEYWORDSLearning and memory function, Voluntary wheel running exercise, Plasminogen activator inhibitor-1 (pai-1), Mirna (mir)-30b
CITE THIS PAPER
Sun Wei, WU Qiao, Effects of Voluntary Wheel Running Exercise on Learning and Memory Function of Young Mice and Related Mechanisms. MEDS Chinese Medicine (2021) 3: 143-150. DOI: http://dx.doi.org/10.23977/medcm.2021.030230
 Christie BR, Cameron HA. Neurogenesis in the adult hippocampus.Hippocampus.2006;16(3):199-207.
 Hillman CH, Biggan JR. A Review of Childhood Physical Activity, Brain, and Cognition: Perspectives on the Future. Pediatric exercise science.2017;29(2):170-176.
 Adlard PA, Perreau VM, Engesser-Cesar C, Cotman CW. The timecourse of induction of brain-derived neurotrophic factor mRNA and protein in the rat hippocampus following voluntary exercise. Neuroscience letters.2004;363(1):43-48.
 Anderson BJ, Rapp DN, Baek DH, McCloskey DP, Coburn-Litvak PS, Robinson JK. Exercise influences spatial learning in the radial arm maze. Physiology & behavior.2000;70(5):425-429.
 van Praag H, Christie BR, Sejnowski TJ, Gage FH. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proceedings of the National Academy of Sciences of the United States of America.1999;96(23):13427-13431.
 Ogoh S. Relationship between cognitive function and regulation of cerebral blood flow. The journal of physiological sciences : JPS. 2017;67(3):345-351.
 de la Monte SM, Tong M. Brain metabolic dysfunction at the core of Alzheimer's disease. Biochemical pharmacology.2014;88(4):548-559.
 Hua Y, Xi G, Keep RF, Wu J, Jiang Y, Hoff JT. Plasminogen activator inhibitor-1 induction after experimental intracerebral hemorrhage. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2002;22(1):55-61.
 Eitzman DT, Westrick RJ, Xu Z, Tyson J, Ginsburg D. Plasminogen activator inhibitor-1 deficiency protects against atherosclerosis progression in the mouse carotid artery. Blood.2000;96(13):4212-4215.
 Kohler HP, Grant PJ. Plasminogen-activator inhibitor type 1 and coronary artery disease.The New England journal of medicine.2000;342(24):1792-1801.
 Zhu ED, Li N, Li BS, et al. miR-30b, down-regulated in gastric cancer, promotes apoptosis and suppresses tumor growth by targeting plasminogen activator inhibitor-1. PloS one.2014;9(8):e106049.
 Frith E, Loprinzi PD. Physical activity and cognitive function among older adults with hypertension. Journal of hypertension.2017;35(6):1271-1275.
 Monnier A, Garnier P, Quirie A, et al. Effect of short-term exercise training on brain-derived neurotrophic factor signaling in spontaneously hypertensive rats. Journal of hypertension.2017;35(2):279-290.
 Chang YK, Alderman BL, Chu CH, Wang CC, Song TF, Chen FT. Acute exercise has a general facilitative effect on cognitive function: A combined ERP temporal dynamics and BDNF study. Psychophysiology.2017;54(2):289-300.
 Denorme F, Wyseure T, Peeters M, et al. Inhibition of Thrombin-Activatable Fibrinolysis Inhibitor and Plasminogen Activator Inhibitor-1 Reduces Ischemic Brain Damage in Mice. Stroke.2016;47(9):2419-2422.
 Seferovic MD, Gupta MB. Increased Umbilical Cord PAI-1 Levels in Placental Insufficiency Are Associated with Fetal Hypoxia and Angiogenesis. Disease markers.2016;2016:7124186.
 Ji Y, Meng QH, Wang ZG. Changes in the coagulation and fibrinolytic system of patients with subarachnoid hemorrhage.Neurologia medico-chirurgica.2014;54(6):457-464.
 Thogersen AM, Jansson JH, Boman K, et al. High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor. Circulation.1998;98(21):2241-2247.
 Hamsten A, de Faire U, Walldius G, et al. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet.1987;2(8549):3-9.
 Jiang H, Li X, Chen S, et al. Plasminogen Activator Inhibitor-1 in depression: Results from Animal and Clinical Studies. Scientific reports.2016;6:30464.
 Oszajca K, Wronski K, Janiszewska G, Bienkiewicz M, Bartkowiak J, Szemraj J. The study of t-PA, u-PA and PAI-1 genes polymorphisms in patients with abdominal aortic aneurysm.Molecular biology reports.2014;41(5):2859-2864.
 Inoue K. [MicroRNA function in animal development]. Tanpakushitsukakusankoso.Protein, nucleic acid, enzyme.2007;52(3):197-204.
 Williams AE, Moschos SA, Perry MM, Barnes PJ, Lindsay MA. Maternally imprinted microRNAs are differentially expressed during mouse and human lung development. Developmental dynamics : an official publication of the American Association of Anatomists. 2007;236(2):572-580.
 Li X, Yu Z, Li Y, et al. The tumor suppressor miR-124 inhibits cell proliferation by targeting STAT3 and functions as a prognostic marker for postoperative NSCLC patients. International journal of oncology.2015;46(2):798-808.
 Lv ZC, Fan YS, Chen HB, Zhao DW. Investigation of microRNA-155 as a serum diagnostic and prognostic biomarker for colorectal cancer.Tumourbiology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2015;36(3):1619-1625.
 Mellios N, Galdzicka M, Ginns E, et al. Gender-specific reduction of estrogen-sensitive small RNA, miR-30b, in subjects with schizophrenia. Schizophrenia bulletin.2012;38(3):433-443.
 Figure legends
 Fig. 1 Expression levels of PAI-1 in hippocampal and blood tissues.
 (A-B) The mRNA expression levels of PAI-1 were detected with the quantitative real-time PCR in the hippocampal (A) and blood (B) tissues, respectively. (C-D) The protein expression levels of PAI-1 in the hippocampal (C) and blood (D) tissues were detected with the Western blot analysis and ELISA, respectively. Compared with the control group, * P < 0.05, ** P < 0.01.
 Fig. 2 Dual-luciferase reporter assay.
 Dual-luciferase reporter assay was performed to confirm the interaction between PAI-1 3’-UTR and miR-30b. Compared with the NC group, * P < 0.05, ** P < 0.01.
 Fig. 3 Expression levels of miR-30b in hippocampal and blood tissues.
 The expression levels of miR-30b were detected with the quantitative real-time PCR in the hippocampal (A) and blood (B) tissues, respectively. Compared with the control group, * P < 0.05, ** P < 0.01.