Regulatory role of microRNA-30b and plasminogen activator inhibitor-1 in the pathogenesis of cognitive impairment

Li,Xiuqin; Gao,Yong; Meng,Zhaoyun; Zhang,Cui; Qi,Qinde

doi:10.3892/etm.2016.3162

Regulatory role of microRNA-30b and plasminogen activator inhibitor-1 in the pathogenesis of cognitive impairment

Authors:
- Xiuqin Li
- Yong Gao
- Zhaoyun Meng
- Cui Zhang
- Qinde Qi
View Affiliations

Affiliations: Second Department of Health, Laiwu Hospital Affiliated to Taishan Medical University, Laiwu, Shandong 271100, P.R. China, Department of Neurosurgery, Laiwu Hospital Affiliated to Taishan Medical University, Laiwu, Shandong 271100, P.R. China, Department of Neurology, Laiwu Hospital Affiliated to Taishan Medical University, Laiwu, Shandong 271100, P.R. China
Published online on: March 15, 2016 https://doi.org/10.3892/etm.2016.3162
Pages: 1993-1998

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to investigate the role of plasminogen activator inhibitor‑1 (PAI‑1) in drug‑induced early cognitive impairment and the underlying mechanism concerning microRNA (miR)‑30b. A mouse model of cognitive impairment was established by intraperitoneal injection of scopolamine (2 mg/kg body weight) for 13 days. Behavioral performance was assessed using the Morris water maze (MWM) test. The mRNA expression levels of PAI‑1 and miR‑30b were detected using quantitative polymerase chain reaction (qPCR). The protein expression levels of PAI‑1 in the hippocampus and blood were determined using western blot analysis and enzyme‑linked immunosorbent assays. The MWM test demonstrated that, on days 3 and 4, the escape latency was significantly elevated in the model mice in comparison with control group (P<0.05). In addition, the length of swimming path was significantly increased (P<0.05), while the number of times of crossing the platform location was significantly reduced in the model mouse group (P<0.05) in comparison with the control group. qPCR demonstrated that the mRNA expression levels of PAI‑1 in the model mice was significantly elevated in the hippocampus and blood in comparison with the control group (P<0.01). Furthermore, western blot analysis and enzyme‑linked immunosorbent assay demonstrated that the protein expression levels of PAI‑1 were significantly elevated in the hippocampus and blood in the model group, in comparison with the control group (P<0.05). Notably, the levels of miR‑30b in the hippocampus and blood were significantly decreased in the model mice in comparison with the control group (P<0.01). To conclude, the expression levels of PAI‑1 were significantly elevated in mice with scopolamine‑induced cognitive impairment, which may be associated with the downregulation of miR‑30b. The findings from the present study suggest that miR‑30b may be involved in the regulation of PAI‑1, which would contribute to the pathogenesis of cognitive impairment.

View Figures

View References

1	Shen X, Li Y and Xu L: Correlation between arterial microemboli and vascular cognitive impairment in patients with acute cerebral infarction. Zhong Guo Lao Nian Xue Za Zhi She. 33:1400–1402. 2013.(In Chinese).
2	Miura R and Hattori H: Overview and assessment of cognitive function in interpreting postoperative cognitive dysfunction. Masui. 63:1188–1195. 2014.(In Japanese). PubMed/NCBI
3	Li S, Okonkwo O, Albert M and Wang MC: Variation in Variables that Predict Progression from MCI to AD Dementia over Duration of Follow-up. Am J Alzheimers Dis (Columbia). 2:12–28. 2013.PubMed/NCBI
4	Petrella JR: Neuroimaging and the search for a cure for Alzheimer disease. Radiology. 269:671–691. 2013. View Article : Google Scholar : PubMed/NCBI
5	de la Monte SM and Tong M: Brain metabolic dysfunction at the core of Alzheimer's disease. Biochem Pharmacol. 88:548–559. 2014. View Article : Google Scholar : PubMed/NCBI
6	Banerjee G, Wilson D, Jäger HR and Werring DJ: Novel imaging techniques in cerebral small vessel diseases and vascular cognitive impairment. Biochim Biophys Acta. 10–Dec;2015.(Epub ahead of print).
7	Anisimova AV, Kolesnikova TI, Iutskova EV, Galkin SS and Zimin IA: An impact of neuroprotective therapy on blood rheological and morphodensitometric parameters in patients with chronic cerebral ischemia. Zh Nevrol Psikhiatr Im S S Korsakova. 114:72–80. 2014.(in Russian). PubMed/NCBI
8	Hua Y, Xi G, Keep RF, Wu J, Jiang Y and Hoff JT: Plasminogen activator inhibitor-1 induction after experimental intracerebral hemorrhage. J Cereb Blood Flow Metab. 22:55–61. 2002. View Article : Google Scholar : PubMed/NCBI
9	Kohler HP and Grant PJ: Plasminogen-activator inhibitor type 1 and coronary artery disease. N Engl J Med. 342:1792–1801. 2000. View Article : Google Scholar : PubMed/NCBI
10	Eitzman DT, Westrick RJ, Xu Z, Tyson J and Ginsburg D: Plasminogen activator inhibitor-1 deficiency protects against atherosclerosis progression in the mouse carotid artery. Blood. 96:4212–4215. 2000.PubMed/NCBI
11	Zhu ED, Li N, Li BS, Li W, Zhang WJ, Mao XH, Guo G, Zou QM and Xiao B: miR-30b, down-regulated in gastric cancer, promotes apoptosis and suppresses tumor growth by targeting plasminogen activator inhibitor-1. PLoS One. 9:e1060492014. View Article : Google Scholar : PubMed/NCBI
12	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-tie quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
13	Hildreth KL and Church S: Evaluation and management of the elderly patient presenting with cognitive complaints. Med Clin North Am. 99:311–335. 2015. View Article : Google Scholar : PubMed/NCBI
14	Kapasi A and Schneider JA: Vascular contributions to cognitive impairment, clinical Alzheimer's disease, and dementia in older persons. Biochim Biophys Acta. 5–Jan;2016.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
15	Mishra D, Sharma S, Gupta S, Das M and Chauhan D: Acute cysticercal meningitis – missed diagnosis. Indian J Pediatr. 73:835–837. 2006. View Article : Google Scholar : PubMed/NCBI
16	Armato U, Chakravarthy B, Pacchiana R and Whitfield JF: Alzheimer's disease: An update of the roles of receptors, astrocytes and primary cilia. Int J Mol Med. 31:3–10. 2013.PubMed/NCBI
17	Christie BR and Cameron HA: Neurogenesis in the adult hippocampus. Hippocampus. 16:199–207. 2006. View Article : Google Scholar : PubMed/NCBI
18	Ikonomovic MD, Abrahamson EE, Isanski BA, Wuu J, Mufson EJ and DeKosky ST: Superior frontal cortex cholinergic axon density in mild cognitive impairment and early Alzheimer disease. Arch Neurol. 64:1312–1317. 2007. View Article : Google Scholar : PubMed/NCBI
19	Ortega A, del Guante MA, Prado-Alcalá RA and Alemán V: Changes in rat brain muscarinic receptors after inhibitory avoidance learning. Life Sci. 58:799–809. 1996. View Article : Google Scholar : PubMed/NCBI
20	Jean L, Thomas B, Tahiri-Alaoui A, Shaw M and Vaux DJ: Heterologous amyloid seeding: Revisiting the role of acetylcholinesterase in Alzheimer's disease. PLoS One. 2:e652–e660. 2007. View Article : Google Scholar : PubMed/NCBI
21	Geula C, Nagykery N, Nicholas A and Wu CK: Cholinergic neuronal and axonal abnormalities are present early in aging and in Alzheimer disease. J Neuropathol Exp Neurol. 67:309–318. 2008. View Article : Google Scholar : PubMed/NCBI
22	Minger SL, Esiri MM, McDonald B, Keene J, Carter J, Hope T and Francis PT: Cholinergic deficits contribute to behavioral disturbance in patients with dementia. Neurology. 55:1460–1467. 2000. View Article : Google Scholar : PubMed/NCBI
23	Erren M, Reinecke H, Junker R, Fobker M, Schulte H, Schurek JO, Kropf J, Kerber S, Breithardt G, Assmann G and Cullen P: Systemic inflammatory parameters in patients with atherosclerosis of the coronary and peripheral arteries. Arterioscler Thromb Vasc Biol. 19:2355–2363. 1999. View Article : Google Scholar : PubMed/NCBI
24	Hamsten A, de Faire U, Walldius G, Dahlén G, Szamosi A, Landou C, Blombäck M and Wiman B: Plasminogen activator inhibitor in plasma: Risk factor for recurrent myocardial infarction. Lancet. 2:3–9. 1987. View Article : Google Scholar : PubMed/NCBI
25	Thögersen AM, Jansson JH, Boman K, Nilsson TK, Weinehall L, Huhtasaari F and Hallmans G: 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. 98:2241–2247. 1998. View Article : Google Scholar : PubMed/NCBI
26	Lupu F, Bergonzelli GE, Heim DA, Cousin E, Genton CY, Bachmann F and Kruithof EK: Localization and production of plasminogen activator inhibitor-1 in human healthy and atherosclerotic arteries. Arterioscler Thromb. 13:1090–1100. 1993. View Article : Google Scholar : PubMed/NCBI
27	Lupu F, Heim DA, Bachmann F, Hurni M, Kakkar VV and Kruithof EK: Plasminogen activator expression in human atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 15:1444–1455. 1995. View Article : Google Scholar : PubMed/NCBI
28	Olexa P and Olexová M: Plasminogen activator inhibitor-l (PAI-1), ischemic heart disease and diabetes mellitus. Vnitr Lek. 49:222–226. 2003.(In Slovak). PubMed/NCBI
29	Rouch A, Vanucci-Bacqué C, Bedos-Belval F and Baltas M: Small molecules inhibitors of plasminogen activator inhibitor-1 - an overview. Eur J Med Chem. 92:619–636. 2015. View Article : Google Scholar : PubMed/NCBI
30	Jokinen H, Gonçalves N, Vigário R, Lipsanen J, Fazekas F, Schmidt R, Barkhof F, Madureira S, Verdelho A, Inzitari D, et al: Early-stage white matter lesions detected by multispectral MRI segmentation predict progressive cognitive decline. Front Neurosci. 9:4552015. View Article : Google Scholar : PubMed/NCBI
31	Matsuura Y, Yamashita A, Iwakiri T, Sugita C, Okuyama N, Kitamura K and Asada Y: Vascular wall hypoxia promotes arterial thrombus formation via augmentation of vascular thrombogenicity. Thromb Haemost. 114:158–172. 2015. View Article : Google Scholar : PubMed/NCBI
32	Inoue K: MicroRNA function in animal development. Tanpakushitsu Kakusan Koso. 52:197–204. 2007.(In Japanese). PubMed/NCBI
33	Williams AE, Moschos SA, Perry MM, Barnes PJ and Lindsay MA: Maternally imprinted microRNAs are differentially expressed during mouse and human lung development. Dev Dyn. 236:572–580. 2007. View Article : Google Scholar : PubMed/NCBI
34	Li X, Yu Z, Li Y, Liu S, Gao C, Hou X, Yao R and Cui L: The tumor suppressor miR-124 inhibits cell proliferation by targeting STAT3 and functions as a prognostic marker for postoperative NSCLC patients. Int J Oncol. 46:798–808. 2015.PubMed/NCBI
35	Lv ZC, Fan YS, Chen HB and Zhao DW: Investigation of microRNA-155 as a serum diagnostic and prognostic biomarker for colorectal cancer. Tumour Biol. 36:1619–1625. 2015. View Article : Google Scholar : PubMed/NCBI
36	Mellios N, Galdzicka M, Ginns E, Baker SP, Rogaev E, Xu J and Akbarian S: Gender-specific reduction of estrogen-sensitive small RNA, miR-30b, in subjects with schizophrenia. Schizophr Bull. 38:433–443. 2012. View Article : Google Scholar : PubMed/NCBI