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Research article
Mouwang Zhou
Peking University Third Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1553-0613
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Abstract
Background Endogenous α-synuclein (α-Syn) is involved in many pathophysiological processes in the secondary injury stage after acute spinal cord injury (SCI), and the mechanism governing these functions has not been thoroughly elucidated to date. This research aims to characterize the effect of α-Syn knockdown on transcriptional levels after SCI and to determine the mechanisms underlying α-Syn activity based on RNA-seq. Result The establishment of a rat model of lentiviral vector-mediated knockdown of α-Syn in Sprague-Dawley rats with T3 spinal cord contusion (LV_SCI group). The results of the RNA-seq analysis showed that there were 337 differentially expressed genes (DEGs) between the SCI group and the LV_SCI group, and 153 DEGs specific to LV_SCI between the (SCI vs LV_SCI) and (SCI vs CON) comparisons . The top 20 biological transition terms were identified by Gene ontology (GO) analysis. The Kyoto Gene and Genomic Encyclopedia (KEGG) analysis showed that the LV_SCI group significantly upregulated the cholinergic synaptic & nicotine addiction and the neuroactive ligand receptor interaction signaling pathway. Enriched chord analysis analyzes key genes. Further cluster analysis, gene and protein interaction network analysis and RT-qPCR results showed that Chrm2 and Chrnb2 together significantly in both pathways. The proliferation of muscarinic cholinergic receptor subtype 2 (Chrm2) and nicotinic cholinergic receptor subtype β2 (Chrnb2), and the neurogenesis were elevated in the injury site of LV_SCI group by immunofluorescence. Further by subcellular localization, the LV_SCI group enhanced the expression of Chrnb2 at the cell membrane. Conclusion Knockdown of α-Syn after SCI enhance motor function and promote neurogenesis probably through enhancing cholinergic signaling pathways and neuroreceptor interactions. This study not only further clarifies the understanding of the mechanism of knockdown of α-Syn on SCI but also helps to guide the treatment strategy for SCI.
Keywords
Spinal cord injury, α-Synuclein, RNA-seq, Cholinergic synapse pathway, Neurogenesis
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- AdditionalFile13.pdf
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- AdditionalFile9.pdf
- AdditionalFile2.xlsx
- AdditionalFile5.xls
- AdditionalFile6.xls
- AdditionalFile81.xlsx
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CURRENT STATUS: Published
View the published article at BMC Genomics.
No community comments so far
Editorial decision: Accept
On 30 Oct, 2019
Editor assigned
On 28 Oct, 2019
Submission checks complete
On 27 Oct, 2019
Editor invited
On 27 Oct, 2019
No comments provided
Editorial decision: Minor revision
On 23 Oct, 2019
Reviewer #1 agreed
On 16 Oct, 2019
Review #1 received
Received 16 Oct, 2019
Reviewers invited
Invitations sent on 15 Oct, 2019
Editor assigned
On 14 Oct, 2019
Submission checks complete
On 13 Oct, 2019
Editor invited
On 13 Oct, 2019
Version 2
Posted 26 Sep, 2019
No comments provided
Review #1 received
Received 10 Oct, 2019
Editorial decision: Minor revision
On 10 Oct, 2019
Review #2 received
Received 04 Oct, 2019
Reviewer #2 agreed
On 24 Sep, 2019
Editor assigned
On 23 Sep, 2019
Reviewers invited
Invitations sent on 23 Sep, 2019
Reviewer #1 agreed
On 23 Sep, 2019
Submission checks complete
On 22 Sep, 2019
Editor invited
On 22 Sep, 2019
No comments provided
Review #2 received
Received 30 Aug, 2019
Editorial decision: Major revision
On 30 Aug, 2019
Review #1 received
Received 27 Aug, 2019
Reviewer #2 agreed
On 21 Aug, 2019
Submission checks complete
On 09 Aug, 2019
Editor assigned
On 09 Aug, 2019
Reviewers invited
Invitations sent on 09 Aug, 2019
Reviewer #1 agreed
On 09 Aug, 2019
Editor invited
On 08 Aug, 2019
First submitted
On 31 Jul, 2019
Metrics
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PDF Downloads: ...
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Subject Areas
Epigenetics & Genomics
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A new preprint design is coming!
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See the published version of this preprint at BMC Genomics.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Mouwang Zhou
Peking University Third Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1553-0613
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Genomics.
No community comments so far
Editorial decision: Accept
On 30 Oct, 2019
Editor assigned
On 28 Oct, 2019
Submission checks complete
On 27 Oct, 2019
Editor invited
On 27 Oct, 2019
No comments provided
Editorial decision: Minor revision
On 23 Oct, 2019
Reviewer #1 agreed
On 16 Oct, 2019
Review #1 received
Received 16 Oct, 2019
Reviewers invited
Invitations sent on 15 Oct, 2019
Editor assigned
On 14 Oct, 2019
Submission checks complete
On 13 Oct, 2019
Editor invited
On 13 Oct, 2019
Version 2
Posted 26 Sep, 2019
No comments provided
Review #1 received
Received 10 Oct, 2019
Editorial decision: Minor revision
On 10 Oct, 2019
Review #2 received
Received 04 Oct, 2019
Reviewer #2 agreed
On 24 Sep, 2019
Editor assigned
On 23 Sep, 2019
Reviewers invited
Invitations sent on 23 Sep, 2019
Reviewer #1 agreed
On 23 Sep, 2019
Submission checks complete
On 22 Sep, 2019
Editor invited
On 22 Sep, 2019
No comments provided
Review #2 received
Received 30 Aug, 2019
Editorial decision: Major revision
On 30 Aug, 2019
Review #1 received
Received 27 Aug, 2019
Reviewer #2 agreed
On 21 Aug, 2019
Submission checks complete
On 09 Aug, 2019
Editor assigned
On 09 Aug, 2019
Reviewers invited
Invitations sent on 09 Aug, 2019
Reviewer #1 agreed
On 09 Aug, 2019
Editor invited
On 08 Aug, 2019
First submitted
On 31 Jul, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Epigenetics & Genomics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Genomics.
Abstract
Background Endogenous α-synuclein (α-Syn) is involved in many pathophysiological processes in the secondary injury stage after acute spinal cord injury (SCI), and the mechanism governing these functions has not been thoroughly elucidated to date. This research aims to characterize the effect of α-Syn knockdown on transcriptional levels after SCI and to determine the mechanisms underlying α-Syn activity based on RNA-seq. Result The establishment of a rat model of lentiviral vector-mediated knockdown of α-Syn in Sprague-Dawley rats with T3 spinal cord contusion (LV_SCI group). The results of the RNA-seq analysis showed that there were 337 differentially expressed genes (DEGs) between the SCI group and the LV_SCI group, and 153 DEGs specific to LV_SCI between the (SCI vs LV_SCI) and (SCI vs CON) comparisons . The top 20 biological transition terms were identified by Gene ontology (GO) analysis. The Kyoto Gene and Genomic Encyclopedia (KEGG) analysis showed that the LV_SCI group significantly upregulated the cholinergic synaptic & nicotine addiction and the neuroactive ligand receptor interaction signaling pathway. Enriched chord analysis analyzes key genes. Further cluster analysis, gene and protein interaction network analysis and RT-qPCR results showed that Chrm2 and Chrnb2 together significantly in both pathways. The proliferation of muscarinic cholinergic receptor subtype 2 (Chrm2) and nicotinic cholinergic receptor subtype β2 (Chrnb2), and the neurogenesis were elevated in the injury site of LV_SCI group by immunofluorescence. Further by subcellular localization, the LV_SCI group enhanced the expression of Chrnb2 at the cell membrane. Conclusion Knockdown of α-Syn after SCI enhance motor function and promote neurogenesis probably through enhancing cholinergic signaling pathways and neuroreceptor interactions. This study not only further clarifies the understanding of the mechanism of knockdown of α-Syn on SCI but also helps to guide the treatment strategy for SCI.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
This is a list of supplementary files associated with this preprint. Click to download.
- AdditionalFile1.xlsx
- AdditionalFile10.xls
- AdditionalFile3.xlsx
- AdditionalFile4.xlsx
- AdditionalFile14.pdf
- AdditionalFile16.pdf
- AdditionalFile15.pdf
- AdditionalFile13.pdf
- AdditionalFile8.xls
- AdditionalFile9.pdf
- AdditionalFile2.xlsx
- AdditionalFile5.xls
- AdditionalFile6.xls
- AdditionalFile81.xlsx
- AdditionalFile12.xlsx
- AdditionalFile11.xlsx
- AdditionalFile7.xls
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