Frontiers Journal of Neurology & Neuroscience

Upregulation Of Astrocyte Elevated Gene (AEG-1) Promotes Axon Regeneration After Spinal Cord Injury

Abstract

Spinal cord injury (SCI) is one of the major types of mammalian central nervous system (CNS) injuries and any injury to the CNS can cause permanent functional disability due to the inability of CNS axons to regenerate. In this study we demonstrate by manipulating expression of protein molecule named astrocyte elevated gene-1 (AEG-1/ also known as MDTH, LYRIC1) that axon regeneration in the CNS is possible. Our microarray analysis of spinal cord injury (SCI) suggests that AEG-1 has a role in CNS axon regeneration. We found that AEG-1 was significantly up-regulated in regenerating pSN+DC lesions compared with intact control and non-regenerating DC lesion models.  We also observed up-regulation of AEG-1 by up to 65 fold in regenerating SN injury model, correlating with axon regeneration. Semi-quantitative RT-PCR was used to confirm our microarray data along with immunohistochemistry and western blot to analyse AEG-1 protein levels.  We found high levels of AEG-1 mRNA and protein in both regenerating SN and pSN+DC compared with non-regenerating DC or intact controls, with pSN+DC model showing the greatest levels of AEG-1 mRNA and protein. Moreover, knockdown of AEG-1 using short interfering RNA (siRNA) in 3 days cultured dorsal root ganglion neurons (DRGN) significantly suppressed DRGN neurite outgrowth suggesting that high levels of AEG-1 are required for axon regeneration. The mechanism by which AEG-1 promotes axonal regeneration is not yet known but we conclude that upregulation of AEG-1 plays a major role in axonal regeneration and could be harnessed to promote regeneration in the CNS of spinal injured patients.

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