Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
General Research Article

Identification and Validation of Synapse-related Hub Genes after Spinal Cord Injury by Bioinformatics Analysis

Author(s): Mengting Shi, Haipeng Xu, Rong Hu, Yi Chen, Xingying Wu, Bowen Chen and Ruijie Ma*

Volume 27, Issue 4, 2024

Published on: 01 June, 2023

Page: [599 - 610] Pages: 12

DOI: 10.2174/1386207326666230426151114

Price: $65

Abstract

Background: Spinal cord injury (SCI) is a neurological disease with high morbidity and mortality. Previous studies have shown that abnormally expressed synapse-related genes are closely related to the occurrence and development of SCI. However, little is known about the interaction of these aberrantly expressed genes and the molecular mechanisms that play a role in the injury response. Therefore, deeply exploring the correlation between synapse-related genes and functional recovery after spinal cord injury and the molecular regulation mechanism is of great significance.

Methods: First, we selected the function GSE45006 dataset to construct three clinically meaningful gene modules by hierarchical clustering analysis in 4 normal samples and 20 SCI samples. Subsequently, we performed functional and pathway enrichment analyses of key modules.

Results: The results showed that related module genes were significantly enriched in synaptic structures and functions, such as the regulation of synaptic membranes and membrane potential. A protein-protein interaction network (PPI) was constructed to identify 10 hub genes of SCI, and the results showed that Snap25, Cplx1, Stxbp1, Syt1, Rims1, Rab3a, Syn2, Syn1, Cask, Lin7b were most associated with SCI. Finally, these hub genes were further verified by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR) in the spinal cord tissues of the blank group and SCI rats, and it was found that the expression of these hub genes was significantly decreased in the spinal cord injury compared with the blank group (P ≤ 0.05).

Conclusion: These results suggest that the structure and function of synapses play an important role after spinal cord injury. Our study helps to understand the underlying pathogenesis of SCI patients further and identify new targets for SCI treatment.

Keywords: Spinal cord injury, WGCNA, synapse, hub genes, morbidity, mortality.

« Previous Next »
Graphical Abstract

[1]
Li, Y.; Ritzel, R.M.; Khan, N.; Cao, T.; He, J.; Lei, Z.; Matyas, J.J.; Sabirzhanov, B.; Liu, S.; Li, H.; Stoica, B.A.; Loane, D.J.; Faden, A.I.; Wu, J. Delayed microglial depletion after spinal cord injury reduces chronic inflammation and neurodegeneration in the brain and improves neurological recovery in male mice. Theranostics, 2020, 10(25), 11376-11403.
[http://dx.doi.org/10.7150/thno.49199] [PMID: 33052221]
[2]
Rubiano, A.M.; Carney, N.; Chesnut, R.; Puyana, J.C. Global neurotrauma research challenges and opportunities. Nature, 2015, 527(7578), S193-S197.
[http://dx.doi.org/10.1038/nature16035] [PMID: 26580327]
[3]
Huber, E.; David, G.; Thompson, A.J.; Weiskopf, N.; Mohammadi, S.; Freund, P. Dorsal and ventral horn atrophy is associated with clinical outcome after spinal cord injury. Neurology, 2018, 90(17), e1510-e1522.
[http://dx.doi.org/10.1212/WNL.0000000000005361] [PMID: 29592888]
[4]
Gwak, Y.S.; Hulsebosch, C.E. GABA and central neuropathic pain following spinal cord injury. Neuropharmacology, 2011, 60(5), 799-808.
[http://dx.doi.org/10.1016/j.neuropharm.2010.12.030] [PMID: 21216257]
[5]
Chen, J.; Cui, Z.; Yang, S.; Wu, C.; Li, W.; Bao, G.; Xu, G.; Sun, Y.; Wang, L.; Zhang, J. The upregulation of annexin A2 after spinal cord injury in rats may have implication for astrocyte proliferation. Neuropeptides, 2017, 61, 67-76.
[http://dx.doi.org/10.1016/j.npep.2016.10.007] [PMID: 27836325]
[6]
Figueroa, J.D.; Serrano-Illan, M.; Licero, J.; Cordero, K.; Miranda, J.D.; De Leon, M. Fatty acid binding protein 5 modulates docosahexaenoic acid-induced recovery in rats undergoing spinal cord injury. J. Neurotrauma, 2016, 33(15), 1436-1449.
[http://dx.doi.org/10.1089/neu.2015.4186] [PMID: 26715431]
[7]
Berglund, A.; Putney, R.M.; Hamaidi, I.; Kim, S. Epigenetic dysregulation of immune-related pathways in cancer: Bioinformatics tools and visualization. Exp. Mol. Med., 2021, 53(5), 761-771.
[http://dx.doi.org/10.1038/s12276-021-00612-z] [PMID: 33963293]
[8]
Zhou, Q.; Feng, X.; Ye, F.; Lei, F.; Jia, X.; Feng, D. miR-27a promotion resulting from silencing of HDAC3 facilitates the recovery of spinal cord injury by inhibiting PAK6 expression in rats. Life Sci., 2020, 260, 118098.
[http://dx.doi.org/10.1016/j.lfs.2020.118098] [PMID: 32679145]
[9]
Hilton, B.J.; Husch, A.; Schaffran, B.; Lin, T.; Burnside, E.R.; Dupraz, S.; Schelski, M.; Kim, J.; Müller, J.A.; Schoch, S.; Imig, C.; Brose, N.; Bradke, F. An active vesicle priming machinery suppresses axon regeneration upon adult CNS injury. Neuron, 2022, 110(1), 51-69.
[http://dx.doi.org/10.1016/j.neuron.2021.10.007] [PMID: 34706221]
[10]
Chen, B.; Li, Y.; Yu, B.; Zhang, Z.; Brommer, B.; Williams, P.R.; Liu, Y.; Hegarty, S.V.; Zhou, S.; Zhu, J.; Guo, H.; Lu, Y.; Zhang, Y.; Gu, X.; He, Z. Reactivation of dormant relay pathways in injured spinal cord by KCC2 manipulations. Cell, 2018, 174(6), 1599.
[http://dx.doi.org/10.1016/j.cell.2018.08.050] [PMID: 30193115]
[11]
Suzuki, K.; Elegheert, J.; Song, I.; Sasakura, H.; Senkov, O.; Matsuda, K.; Kakegawa, W.; Clayton, A.J.; Chang, V.T.; Ferrer-Ferrer, M.; Miura, E.; Kaushik, R.; Ikeno, M.; Morioka, Y.; Takeuchi, Y.; Shimada, T.; Otsuka, S.; Stoyanov, S.; Watanabe, M.; Takeuchi, K.; Dityatev, A.; Aricescu, A.R.; Yuzaki, M. A synthetic synaptic organizer protein restores glutamatergic neuronal circuits. Science, 2020, 369(6507), eabb4853.
[http://dx.doi.org/10.1126/science.abb4853] [PMID: 32855309]
[12]
Goldshmit, Y.; Banyas, E.; Bens, N.; Yakovchuk, A.; Ruban, A. Blood glutamate scavengers and exercises as an effective neuroprotective treatment in mice with spinal cord injury. J. Neurosurg. Spine, 2020, 33(5), 692-704.
[http://dx.doi.org/10.3171/2020.4.SPINE20302] [PMID: 32619986]
[13]
Zhang, X.; Zhong, Z.; Xiang, Y.; Hu, X.; Wang, Y.; Zeng, X.; Wang, X.; Xia, Q.; Wang, T. Synaptosomal-associated protein 25 may be an intervention target for improving sensory and locomotor functions after spinal cord contusion. Neural Regen. Res., 2017, 12(6), 969-976.
[http://dx.doi.org/10.4103/1673-5374.208592] [PMID: 28761431]
[14]
Liu, P.; Song, C.; Wang, C.; Li, Y.; Su, L.; Li, J.; Zhao, Q.; Wang, Z.; Shen, M.; Wang, G.; Yu, Y.; Zhang, L. Spinal SNAP-25 regulates membrane trafficking of GluA1-containing AMPA receptors in spinal injury–induced neuropathic pain in rats. Neurosci. Lett., 2020, 715, 134616.
[http://dx.doi.org/10.1016/j.neulet.2019.134616] [PMID: 31705923]
[15]
Rizo, J. Mechanism of neurotransmitter release coming into focus. Protein Sci., 2018, 27(8), 1364-1391.
[http://dx.doi.org/10.1002/pro.3445] [PMID: 29893445]
[16]
Coppola, T.; Magnin-Lüthi, S.; Perret-Menoud, V.; Gattesco, S.; Schiavo, G.; Regazzi, R. Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-25, and synaptotagmin. J. Biol. Chem., 2001, 276(35), 32756-32762.
[http://dx.doi.org/10.1074/jbc.M100929200] [PMID: 11438518]
[17]
Park, C.; Chen, X.; Tian, C.L.; Park, G.N.; Chenouard, N.; Lee, H.; Yeo, X.Y.; Jung, S.; Tsien, R.W.; Bi, G.Q.; Park, H. Unique dynamics and exocytosis properties of GABAergic synaptic vesicles revealed by three-dimensional single vesicle tracking. Proc. Natl. Acad. Sci., 2021, 118(9), e2022133118.
[http://dx.doi.org/10.1073/pnas.2022133118] [PMID: 33622785]
[18]
Chang, S.; Reim, K.; Pedersen, M.; Neher, E.; Brose, N.; Taschenberger, H. Complexin stabilizes newly primed synaptic vesicles and prevents their premature fusion at the mouse calyx of held synapse. J. Neurosci., 2015, 35(21), 8272-8290.
[http://dx.doi.org/10.1523/JNEUROSCI.4841-14.2015] [PMID: 26019341]
[19]
Wang, X.; Gong, J.; Zhu, L.; Wang, S.; Yang, X.; Xu, Y.; Yang, X.; Ma, C. Munc13 activates the Munc18‐1/syntaxin‐1 complex and enables Munc18‐1 to prime SNARE assembly. EMBO J., 2020, 39(16), e103631.
[http://dx.doi.org/10.15252/embj.2019103631] [PMID: 32643828]
[20]
Stepien, K.P.; Rizo, J. Synaptotagmin-1–, Munc18-1–, and Munc13-1–dependent liposome fusion with a few neuronal SNAREs. Proc. Natl. Acad. Sci. USA, 2021, 118(4), e2019314118.
[http://dx.doi.org/10.1073/pnas.2019314118] [PMID: 33468652]
[21]
Russ, N.; Schröder, M.; Berger, B.T.; Mandel, S.; Aydogan, Y.; Mauer, S.; Pohl, C.; Drewry, D.H.; Chaikuad, A.; Müller, S.; Knapp, S. Design and development of a chemical probe for pseudokinase Ca2+/calmodulin-dependent Ser/Thr kinase. J. Med. Chem., 2021, 64(19), 14358-14376.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00845] [PMID: 34543009]
[22]
Schmerl, B.; Gimber, N.; Kuropka, B.; Stumpf, A.; Rentsch, J.; Kunde, S.A.; von Sivers, J.; Ewers, H.; Schmitz, D.; Freund, C.; Schmoranzer, J.; Rademacher, N.; Shoichet, S.A. The synaptic scaffold protein MPP2 interacts with GABAA receptors at the periphery of the postsynaptic density of glutamatergic synapses. PLoS Biol., 2022, 20(3), e3001503.
[http://dx.doi.org/10.1371/journal.pbio.3001503] [PMID: 35312684]
[23]
Brouwer, M.; Farzana, F.; Koopmans, F.; Chen, N.; Brunner, J.W.; Oldani, S.; Li, K.W.; van Weering, J.R.T.; Smit, A.B.; Toonen, R.F.; Verhage, M. SALM 1 controls synapse development by promoting F‐actin/PIP2‐dependent Neurexin clustering. EMBO J., 2019, 38(17), e101289.
[http://dx.doi.org/10.15252/embj.2018101289] [PMID: 31368584]
[24]
Anitei, M.; Cowan, A.E.; Pfeiffer, S.E.; Bansal, R. Role for Rab3a in oligodendrocyte morphological differentiation. J. Neurosci. Res., 2009, 87(2), 342-352.
[http://dx.doi.org/10.1002/jnr.21870] [PMID: 18798275]
[25]
Zhou, H.; Kang, Y.; Shi, Z.; Lu, L.; Li, X.; Chu, T.; Liu, J.; Liu, L.; Lou, Y.; Zhang, C.; Ning, G.; Feng, S.; Kong, X. Identification of differentially expressed proteins in rats with spinal cord injury during the transitional phase using an iTRAQ-based quantitative analysis. Gene, 2018, 677, 66-76.
[http://dx.doi.org/10.1016/j.gene.2018.07.050] [PMID: 30036659]
[26]
Lau, B.Y.B.; Foldes, A.E.; Alieva, N.O.; Oliphint, P.A.; Busch, D.J.; Morgan, J.R. Increased synapsin expression and neurite sprouting in lamprey brain after spinal cord injury. Exp. Neurol., 2011, 228(2), 283-293.
[http://dx.doi.org/10.1016/j.expneurol.2011.02.003] [PMID: 21316361]
[27]
Yin, Y.; Huang, P.; Han, Z.; Wei, G.; Zhou, C.; Wen, J.; Su, B.; Wang, X.; Wang, Y. Collagen nanofibers facilitated presynaptic maturation in differentiated neurons from spinal-cord-derived neural stem cells through MAPK/ERK1/2-Synapsin I signaling pathway. Biomacromolecules, 2014, 15(7), 2449-2460.
[http://dx.doi.org/10.1021/bm500321h] [PMID: 24955924]
[28]
Schmidtko, A.; Luo, C.; Gao, W.; Geisslinger, G.; Kuner, R.; Tegeder, I. Genetic deletion of synapsin II reduces neuropathic pain due to reduced glutamate but increased GABA in the spinal cord dorsal horn. Pain, 2008, 139(3), 632-643.
[http://dx.doi.org/10.1016/j.pain.2008.06.018] [PMID: 18701217]

Rights & Permissions Print Cite
Article Metrics
25
2
© 2024 Bentham Science Publishers | Privacy Policy