Transcriptomic and proteomic analyses reveal the key path-way of the central nervous system axonal growth-inhibitory protein Nogo-A in inhibiting axon regeneration of primary hippocampal neurons

To reveal the potential molecular mechanisms of axon regeneration failure after central neuron injury, transcriptomics and proteomics were used to study the inhibitory effect of Nogo-A, a cen-tral nervous system (CNS) axon growth inhibitory protein, on rat primary hippocampal neurons in vitro as a single factor, which avoided the interference of the complex internal environment in vivo and greatly reduced the number of differential genes and proteins. Primary hippocampal neurons from Sprague-Dawley fetal rats at 17 days gestation were cultured in vitro for 2 days. Nogo-A (200nM) was added to observe the growth of axons, and the control group was added with an equal amount of solvent. On the 7th day, high-throughput transcriptome sequencing (RNA-Seq) and proteomic sequencing were performed to detect and verify differences in gene and protein expression . Compared with the control group, hippocampal neurons of rats treated with Nogo-A showed restricted axon growth and a lower density neural network. Differentially ex-pressed genes and proteins were predominantly involved in the inflammatory response, apopto-sis, and cytoskeleton. Joint correlation analysis revealed that the cAMP -signaling pathway was enriched in environmental information processing. Thus, we demonstrated the characteristics of the mRNA and protein expression profiles in neurons following the action of the CNS axonal growth inhibitory protein Nogo-A and show that the differentially expressed molecules are in-volved in axon regeneration and signaling pathways. Their role in repairing damaged neurons deserves further study.