Investigating the Effects of Ibuprofen on the Gene Expression Profle in Hippocampus of Mice Model of Alzheimer’s Disease through Bioinformatics Analysis

Document Type : Research article

Authors

1 Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) identified effective in many diseases. One of which is neurodegenerative diseases including Alzheimer disease (AD). In this study gross alteration of gene expression in AD mice by ibuprofen treatment is investigated via Protein-protein interaction network (PPI) analysis. Expression profiling of microarray dataset GSE67306 was retrieved from GEO database and analyzed via GEO2R tool. PPI analysis was performed via Cytoscape 3.7.0. and its plug-ins including Network Analyzer, Gene MANIA, and CluePedia. Numbers of 10 central genes including Htr1a, Sstr2, Drd2, Htr1b, Penk, Pomc, Oprm1, Npy, Sst, and Chrm2 were identified as potential biomarkers. However, the role of Penk gene was highlighted. The finding indicates that ibuprofen changes gene expression level of several genes that are involved in AD.

Graphical Abstract

Investigating the Effects of Ibuprofen on the Gene Expression Profle in Hippocampus of Mice Model of Alzheimer’s Disease through Bioinformatics Analysis

Keywords


(1)        Schedin-Weiss S, Inoue M, Hromadkova L, et al. Monoamine oxidase B is elevated in Alzheimer disease neurons, is associated with γ-secretase and regulates neuronal amyloid β-peptide levels. Alzheimer's research & therapy (2017) 9: 1-19.
(2)        Nissen SE, Yeomans ND, Solomon DH, et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. New England Journal of Medicine (2016) 375: 2519-2529.
(3)        Bernard GR, Wheeler AP, Russell JA, et al. The effects of ibuprofen on the physiology and survival of patients with sepsis. New England Journal of Medicine (1997) 336: 912-918.
(4)        Harris RE. Ibuprofen in the prevention and therapy of cancer. Ibuprofen: Discovery, Development and Therapeutics (2015) 518-546.
(5)        Gao X, Chen H, Schwarzschild MA, Ascherio A. Use of ibuprofen and risk of Parkinson disease. Neurology (2011) 76: 863-869.
(6)        Woodling NS, Colas D, Wang Q, et al. Cyclooxygenase inhibition targets neurons to prevent early behavioural decline in Alzheimer’s disease model mice. Brain (2016)139: 2063-2081.
(7)        Angadi SS, Karn A. Ibuprofen induced Stevens-Johnson syndrome-toxic epidermal necrolysis in Nepal. Asia Pacific Allergy (2016) 6: 70-73.
(8)        Ding T, Yang M, Zhang J, et al. Toxicity, degradation and metabolic fate of ibuprofen on freshwater diatom Navicula sp. Journal of hazardous materials (2017) 330: 127-134.
(9)        Weiser T, Richter E, Hegewisch A, Muse DD, Lange R. Efficacy and safety of a fixed-dose combination of ibuprofen and caffeine in the management of moderate to severe dental pain after third molar extraction. European journal of pain (London, England) (2018) 22: 28-38.
(10)      Rainsford K. Ibuprofen in Prevention of Neurodegenerative Diseases. Ibuprofen: Discovery, Development and Therapeutics, chapter 14, (2015) 547-570.
(11)      Choi SH, Aid S, Caracciolo L, et al. Cyclooxygenase‐1 inhibition reduces amyloid pathology and improves memory deficits in a mouse model of Alzheimer's disease. Journal of neurochemistry 2013; 124: 59-68.
(12)      Azodi MZ, Rezaei-Tavirani M, Rostami-Nejad M, Rezaei-Tavirani M. Comparative Bioinformatics Characteristic of Bladder Cancer Stage 2 from Stage 4 Expression Profile: A Network-Based Study. Galen Medical Journal (2018)7:1-8.
(13)      Barrett T, Wilhite SE, Ledoux P, et al. NCBI GEO: archive for functional genomics data sets—update. Nucleic acids research (2012) 41: 991-995.
(14)      Mahboubi M, Rezaei Tavirani M, Mansouri V, Ahmadi NA, Hamdieh M, Rezaei Tavirani M. Protein-Protein Interaction Analysis of Common Top Genes in Obsessive-Compulsive disorder (OCD) and Schizophrenia: Towards New Drug Approach. Iranian Journal of Pharmaceutical Research (2018)
(15)      Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome research (2003) 13: 2498-2504.
(16)      Szklarczyk D, Morris JH, Cook H, et al. The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic acids research (2016) 937.
(17)      Assenov Y, Ramírez F, Schelhorn S-E, Lengauer T, Albrecht M. Computing topological parameters of biological networks. Bioinformatics (2007) 24: 282-284.
(18)      Bindea G, Galon J, Mlecnik B. CluePedia Cytoscape plugin: pathway insights using integrated experimental and in silico data. Bioinformatics (2013) 29: 661-663.
(19)      Swomley AM, Förster S, Keeney JT, et al. Abeta, oxidative stress in Alzheimer disease: evidence based on proteomics studies. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease (2014) 1842: 1248-1257.
(20)      Taylor G, Carter G, Crow T, et al. Recovery and measurement of specific RNA species from postmortem brain tissue: a general reduction in Alzheimer's disease detected by molecular hybridization. Experimental and molecular pathology (1986) 44: 111-116.
(21)      Calon F, Birdi S, Rajput AH, Hornykiewicz O, Bédard PJ, Di Paolo T. Increase of preproenkephalin mRNA levels in the putamen of Parkinson disease patients with levodopa-induced dyskinesias. Journal of Neuropathology & Experimental Neurology (2002) 61: 186-196.
(22)      Anderson AJ, Cummings BJ, Cotman CW. Increased immunoreactivity for Jun-and Fos-related proteins in Alzheimer's disease: association with pathology. Experimental neurology (1994) 125: 286-295.