Gene expression profile of frontal lobe in Parkinson disease based on bioinformatics analysis_West China Medical Journal

Authors：

 WU Xintong ¹ , HONG Peiwei ²

1. Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Geriatrics and Neurology, West China School of Public Health and West China Forth Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

WU Xintong, Email: 36853839@qq.com

Keywords：

Parkinson disease; Frontal lobe; Non-motor symptoms; Psychogenic depression; Bioinformatics analysis

DOI：

10.7507/1002-0179.201904201

Video：

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Objective To conduct a bioinformatics analysis of gene expression profiles in frontal lobe of patients with Parkinson disease (PD), in order to explore the potential mechanism related to depression in PD.Methods All the bioinformatics data before March 20th 2019 were acquired from Gene Expression Omnibus (GEO) database, using " Parkinson disease” as the key word. The species was limited to human (Homo sapiens), and the detective method was limited to expression profiling by array. ImgGEO (Integrative Gene Expression Meta-Analysis from GEO database), DAVID (the Database for Annotation, Visualization and Integrated Discovery), STRING and Cytoscape 3.6.1 software were utilized for data analysis.Results Totally, 45 samples (24 PD cases and 21 healthy controls) were obtained from 2 datasets. We identified 236 differentially expressed genes (DEGs) in the post-mortem frontal lobe between PD cases and healthy controls, in which 146 genes were up-regulated and 90 genes were down-regulated. Based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis, the DEGs were mainly enriched in the structures of postsynaptic membrane, cell membrane component, postsynaptic membrane dense area, and myelin sheath, and were involved in the occurrence of PD, depression, and other diseases. These genes were involved in the biological processes of dopaminergic, glutamate-nergic, GABA-nergic synapses, and some other synapses, as well as several signaling pathways (e.g. mitogen- activated protein kinase signal pathway, p53 signal pathway, and Wnt signal pathway), which were associated with PD and depression pathogenesis. Besides, we found that NFKBIA, NRXN1, and RPL35A were the Hub proteins.Conclusions Gene expression in frontal lobe of patients with PD is associated with the pathogenesis of PD. This study provides a theoretical basis for understanding the mechanism of PD occurrence and progression, as well as the potential mechanism of depression in PD.

Citation： WU Xintong, HONG Peiwei. Gene expression profile of frontal lobe in Parkinson disease based on bioinformatics analysis. West China Medical Journal, 2019, 34(10): 1117-1125. doi: 10.7507/1002-0179.201904201 Copy

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2.	Weintraub D, Moberg PJ, Duda JE, et al. Effect of psychiatric and other nonmotor symptoms on disability in Parkinson’s disease. J Am Geriatr Soc, 2004, 52(5): 784-788.
3.	Alzahrani H, Venneri A. Cognitive and neuroanatomical correlates of neuropsychiatric symptoms in Parkinson’s disease: a systematic review. J Neurol Sci, 2015, 356(1/2): 32-44.
4.	Ubeda-Banon I, Saiz-Sanchez D, de la Rosa-Prieto C, et al. Alpha-synuclein in the olfactory system in Parkinson’s disease: role of neural connections on spreading pathology. Brain Struct Funct, 2014, 219(5): 1513-1526.
5.	Phillipson OT. Alpha-synuclein, epigenetics, mitochondria, metabolism, calcium traffic, & circadian dysfunction in Parkinson’s disease. Ageing Res Rev, 2017, 40: 149-167.
6.	Rutten S, Ghielen I, Vriend C, et al. Anxiety in Parkinson’s disease: symptom dimensions and overlap with depression and autonomic failure. Parkinsonism Relat Disord, 2015, 21(3): 189-193.
7.	蔡彦宁, 温玫, 张愚, 等. 帕金森病患者尾状核中基因表达谱的研究. 中华医学杂志, 2004, 84(14): 1191-1193.
8.	Toro-Dominguez D, Martorell-Marugan J, Lopez-Dominguez R, et al. ImaGEO: integrative gene expression meta-analysis from GEO database. Bioinformatics, 2019, 35(5): 880-882.
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14.	姜立志, 沈丽华, 孙翠. Parkin基因突变和线粒体功能紊乱与帕金森病的相关性. 中国老年学杂志, 2015, 35(11): 3175-3178.
15.	Chaudhuri KR, Schapira AH. Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol, 2009, 8(5): 464-474.
16.	Aarsland D, Larsen JP, Lim NG, et al. Range of neuropsychiatric disturbances in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry, 1999, 67(4): 492-496.
17.	Frisina PG, Borod JC, Foldi NS, et al. Depression in Parkinson’s disease: health risks, etiology, and treatment options. Neuropsychiatr Dis Treat, 2008, 4(1): 81-91.
18.	Reijnders JS, Ehrt U, Weber WE, et al. A systematic review of prevalence studies of depression in Parkinson’s disease. Mov Disord, 2008, 23(2): 183-189.
19.	Ring HA, Bench CJ, Trimble MR, et al. Depression in Parkinson’s disease. a positron emission study. Br J Psychiatry, 1994, 165(3): 333-339.
20.	Feldmann A, Illes Z, Kosztolanyi P, et al. Morphometric changes of gray matter in Parkinson’s disease with depression: a voxel-based morphometry study. Mov Disord, 2008, 23(1): 42-46.
21.	Kostic VS, Agosta F, Petrovic I, et al. Regional patterns of brain tissue loss associated with depression in Parkinson disease. Neurology, 2010, 75(10): 857-863.
22.	刘婷婷, 孟涛, 刘中海, 等. 帕金森病大鼠模型纹状体中谷氨酸、γ-氨基丁酸与多巴胺之间的关系. 神经解剖学杂志, 2011, 27(3): 307-310.
23.	English AW, Liu K, Nicolini JM, et al. Small-molecule trkB agonists promote axon regeneration in cut peripheral nerves. Proc Natl Acad Sci USA, 2013, 110(40): 16217-16222.
24.	Levine AJ, Harris CR, Puzio-Kuter AM. The interfaces between signal transduction pathways: IGF-1/mTor, p53 and the parkinson disease pathway. Oncotarget, 2012, 3(11): 1301-1307.
25.	Culmsee C, Mattson MP. p53 in neuronal apoptosis. Biochem Biophys Res Commun, 2005, 331(3): 761-777.
26.	Vanlandingham JW, Tassabehji NM, Somers RC, et al. Expression profiling of p53-target genes in copper-mediated neuronal apoptosis. Neuromolecular Med, 2005, 7(4): 311-324.
27.	Zhang L, Deng J, Pan Q, et al. Targeted methylation sequencing reveals dysregulated Wnt signaling in Parkinson disease. J Genet Genomics, 2016, 43(10): 587-592.
28.	Zhang M, Huang JJ, Tan XX, et al. Common polymorphisms in the NFKBIA gene and cancer susceptibility: a meta-analysis. Med Sci Monit, 2015, 21: 3186-3196.
29.	Jenkins AK, Paterson C, Wang Y, et al. Neurexin 1 (NRXN1) splice isoform expression during human neocortical development and aging. Mol Psychiatry, 2016, 21(5): 701-706.
30.	Castronovo P, Baccarin M, Ricciardello A, et al. Phenotypic spectrum of NRXN1 mono- and bi-allelic deficiency: a systematic review. Clin Genet, 2019. https://doi.org/10.1111/cge.13537.
31.	Farrar JE, Nater M, Caywood E, et al. Abnormalities of the large ribosomal subunit protein, Rp135a, in Diamond-Blackfan anemia. Blood, 2008, 112(5): 1582-1592.

1. Berg D, Postuma RB, Adler CH, et al. MDS research criteria for prodromal Parkinson’s disease. Mov Disord, 2015, 30(12): 1600-1611.
2. Weintraub D, Moberg PJ, Duda JE, et al. Effect of psychiatric and other nonmotor symptoms on disability in Parkinson’s disease. J Am Geriatr Soc, 2004, 52(5): 784-788.
3. Alzahrani H, Venneri A. Cognitive and neuroanatomical correlates of neuropsychiatric symptoms in Parkinson’s disease: a systematic review. J Neurol Sci, 2015, 356(1/2): 32-44.
4. Ubeda-Banon I, Saiz-Sanchez D, de la Rosa-Prieto C, et al. Alpha-synuclein in the olfactory system in Parkinson’s disease: role of neural connections on spreading pathology. Brain Struct Funct, 2014, 219(5): 1513-1526.
5. Phillipson OT. Alpha-synuclein, epigenetics, mitochondria, metabolism, calcium traffic, & circadian dysfunction in Parkinson’s disease. Ageing Res Rev, 2017, 40: 149-167.
6. Rutten S, Ghielen I, Vriend C, et al. Anxiety in Parkinson’s disease: symptom dimensions and overlap with depression and autonomic failure. Parkinsonism Relat Disord, 2015, 21(3): 189-193.
7. 蔡彦宁, 温玫, 张愚, 等. 帕金森病患者尾状核中基因表达谱的研究. 中华医学杂志, 2004, 84(14): 1191-1193.
8. Toro-Dominguez D, Martorell-Marugan J, Lopez-Dominguez R, et al. ImaGEO: integrative gene expression meta-analysis from GEO database. Bioinformatics, 2019, 35(5): 880-882.
9. Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using David bioinformatics resources. Nat Protoc, 2009, 4(1): 44-57.
10. Huang da W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res, 2009, 37(1): 1-13.
11. Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res, 2019, 47(D1): D607-D613.
12. Chin CH, Chen SH, Wu HH, et al. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol, 2014, 8(4): S11.
13. Tian YY, Tang CJ, Wu J, et al. Parkinson’s disease in China. Neurol Sci, 2011, 32: 23-30.
14. 姜立志, 沈丽华, 孙翠. Parkin基因突变和线粒体功能紊乱与帕金森病的相关性. 中国老年学杂志, 2015, 35(11): 3175-3178.
15. Chaudhuri KR, Schapira AH. Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol, 2009, 8(5): 464-474.
16. Aarsland D, Larsen JP, Lim NG, et al. Range of neuropsychiatric disturbances in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry, 1999, 67(4): 492-496.
17. Frisina PG, Borod JC, Foldi NS, et al. Depression in Parkinson’s disease: health risks, etiology, and treatment options. Neuropsychiatr Dis Treat, 2008, 4(1): 81-91.
18. Reijnders JS, Ehrt U, Weber WE, et al. A systematic review of prevalence studies of depression in Parkinson’s disease. Mov Disord, 2008, 23(2): 183-189.
19. Ring HA, Bench CJ, Trimble MR, et al. Depression in Parkinson’s disease. a positron emission study. Br J Psychiatry, 1994, 165(3): 333-339.
20. Feldmann A, Illes Z, Kosztolanyi P, et al. Morphometric changes of gray matter in Parkinson’s disease with depression: a voxel-based morphometry study. Mov Disord, 2008, 23(1): 42-46.
21. Kostic VS, Agosta F, Petrovic I, et al. Regional patterns of brain tissue loss associated with depression in Parkinson disease. Neurology, 2010, 75(10): 857-863.
22. 刘婷婷, 孟涛, 刘中海, 等. 帕金森病大鼠模型纹状体中谷氨酸、γ-氨基丁酸与多巴胺之间的关系. 神经解剖学杂志, 2011, 27(3): 307-310.
23. English AW, Liu K, Nicolini JM, et al. Small-molecule trkB agonists promote axon regeneration in cut peripheral nerves. Proc Natl Acad Sci USA, 2013, 110(40): 16217-16222.
24. Levine AJ, Harris CR, Puzio-Kuter AM. The interfaces between signal transduction pathways: IGF-1/mTor, p53 and the parkinson disease pathway. Oncotarget, 2012, 3(11): 1301-1307.
25. Culmsee C, Mattson MP. p53 in neuronal apoptosis. Biochem Biophys Res Commun, 2005, 331(3): 761-777.
26. Vanlandingham JW, Tassabehji NM, Somers RC, et al. Expression profiling of p53-target genes in copper-mediated neuronal apoptosis. Neuromolecular Med, 2005, 7(4): 311-324.
27. Zhang L, Deng J, Pan Q, et al. Targeted methylation sequencing reveals dysregulated Wnt signaling in Parkinson disease. J Genet Genomics, 2016, 43(10): 587-592.
28. Zhang M, Huang JJ, Tan XX, et al. Common polymorphisms in the NFKBIA gene and cancer susceptibility: a meta-analysis. Med Sci Monit, 2015, 21: 3186-3196.
29. Jenkins AK, Paterson C, Wang Y, et al. Neurexin 1 (NRXN1) splice isoform expression during human neocortical development and aging. Mol Psychiatry, 2016, 21(5): 701-706.
30. Castronovo P, Baccarin M, Ricciardello A, et al. Phenotypic spectrum of NRXN1 mono- and bi-allelic deficiency: a systematic review. Clin Genet, 2019. https://doi.org/10.1111/cge.13537.
31. Farrar JE, Nater M, Caywood E, et al. Abnormalities of the large ribosomal subunit protein, Rp135a, in Diamond-Blackfan anemia. Blood, 2008, 112(5): 1582-1592.

West China Medical Journal

Gene expression profile of frontal lobe in Parkinson disease based on bioinformatics analysis

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