Transcriptomic analysis of α-synuclein knockdown after T3 spinal cord injury in rats

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. The results of the RNA-SEQ analysis showed that there were 191 differentially expressed genes (DEGs) between the SCI group and the LV_SCI group, and 96 DEGs in the LV_SCI group compared with the sham operation group (CON group). 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 up-regulated the cholinergic synaptic pathway and the neuroactive ligand receptor interaction signaling pathway. Enriched chord analysis analyzes key genes. Further cluster analysis, gene and protein interaction network analysis showed that Chrm2 and Chrnb2 together observed the LV_SCI group to promote the proliferation of Chrm2 and Chrnb2 and the neurogenesis of the injury site by immunofluorescence. Further by subcellular localization, the LV_SCI group enhanced the expression of Chrnb2 at the cell membrane and cell junction. Conclusion Knockdown of α-synuclein after spinal cord injury 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-synuclein on SCI but also helps to guide the treatment strategy for SCI.