Big data differential analysis of microglial cell responses in neurodegenerative diseases

다국어 초록 (Multilingual Abstract)

Microarray technology has become an indispensable tool for monitoring the levels of gene expression in a given organism through organization, analysis, interpretation, and utilization of biological sequences. Importantly, preliminary microarray gene expression differs from experimentally validated gene expression. Generally, microarray analysis of gene expression in microglial cells is used to identify genes in the brain and spinal cord that are responsible for the onset of neurodegenerative diseases; these genes are either upregulated or downregulated. In the present study, 770 genes identified in prior publications, including experimental studies, were analyzed to determine whether these genes encode novel disease genes.
Among the genes published, 340 genes were matched among multiple publications, whereas 430 genes were mismatched; the matched genes were presumed to have the greatest likelihood of contributing to neurodegenerative diseases and thus to be potentially useful target genes for treatment of neurodegenerative diseases. In protein and mRNA expression studies, matched and mismatched genes showed 99% and 97% potentiality, respectively. In addition, some genes identified in microarray analyses were significantly different from those in experimentally validated expression patterns. This study identified novel genes in microglial cells through comparative analysis of published microarray and experimental data on neurodegenerative diseases.

참고문헌 (Reference)

1 Twine NA, "Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease" 6 : e16266-, 2011

2 Sinclair C, "Up-regulation of osteopontin and alphaBeta-crystallin in the normalappearing white matter of multiple sclerosis : an immunohistochemical study utilizing tissue microarrays" 31 : 292-303, 2005

3 Chabas D, "The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease" 294 : 1731-1735, 2001

4 Sweitzer SM, "The differential role of spinal MHC class II and cellular adhesion molecules in peripheral inflammatory versus neuropathic pain in rodents" 125 : 82-93, 2002

5 Lehesjoki AE, "Progressive myoclonus epilepsy of Unverricht-Lundborg type" 40 (40): 23-28, 1999

6 Mootha VK, "PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes" 34 : 267-273, 2003

7 Newton MA, "On differential variability of expression ratios : improving statistical inference about gene expression changes from microarray data" 8 : 37-52, 2001

8 Tsuda M, "Neuropathic pain and spinal microglia : a big problem from molecules in"small"glia" 28 : 101-107, 2005

9 Lassmann H, "Multiple sclerosis : experimental models and reality" 133 : 223-244, 2017

10 Wada R, "Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation" 97 : 10954-10959, 2000

11 Inoue K, "Microglia in neuropathic pain : cellular and molecular mechanisms and therapeutic potential" 19 : 138-152, 2018

12 Carson MJ, "Microglia as liaisons between the immune and central nervous systems : functional implications for multiple sclerosis" 40 : 218-231, 2002

13 Wake H, "Microglia : actively surveying and shaping neuronal circuit structure and function" 36 : 209-217, 2013

14 Brown CW, "Insertion of Inhbb into the Inhba locus rescues the Inhba-null phenotype and reveals new activin functions" 25 : 453-457, 2000

15 Lee CK, "Gene-expression profile of the ageing brain in mice" 25 : 294-297, 2000

16 Jiang YM, "Gene expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis" 57 : 236-251, 2005

17 Trapp BD, "Evidence for synaptic stripping by cortical microglia" 55 : 360-368, 2007

18 Mirnics K, "Disease-specific changes in regulator of G-protein signaling 4(RGS4)expression in schizophrenia" 6 : 293-301, 2001

19 Yamada J, "Differential involvement of perineuronal astrocytes and microglia in synaptic stripping after hypoglossal axotomy" 182 : 1-10, 2011

20 Thacker MA, "CCL2 is a key mediator of microglia activation in neuropathic pain states" 13 : 263-272, 2009

21 Kerr MK, "Analysis of variance for gene expression microarray data" 7 : 819-837, 2000