Abstract
In both the central nervous system (CNS) and the peripheral nervous system (PNS), axonal injury induces changes in neuronal gene expression. In the PNS, a relatively well-characterized alteration in transcriptional activation is known to promote axonal regeneration. This transcriptional cascade includes the neurotrophin Bdnf and the transcription factor Sox11. Although both molecules act to facilitate successful axon regeneration in the PNS, this process does not occur in the CNS. The present study examines the differential expression of Sox11 and Bdnf mRNA isoforms in the PNS and CNS using three experimental paradigms at different time points: (i) the acutely injured CNS (retina after optic nerve crush) and PNS (dorsal root ganglion after sciatic nerve crush), (ii) a CNS regeneration model (retina after optic nerve crush and induced regeneration); and (iii) the retina during a chronic form of central neurodegeneration (the DBA/2J glaucoma model). We find an initial increase of Sox11 in both PNS and CNS after injury; however, the expression of Bdnf isoforms is higher in the PNS relative to the CNS. Sustained upregulation of Sox11 is seen in the injured retina following regeneration treatment, while the expression of two Bdnf mRNA isoforms is suppressed. Furthermore, two isoforms of Sox11 with different 3′UTR lengths are present in the retina, and the long isoform is specifically upregulated in later stages of glaucoma. These results provide insight into the molecular cascades active during axonal injury and regeneration in mammalian neurons.
Highlights
It is well known that neurons of the peripheral nervous system (PNS) have the ability to regrow damaged axons, while neurons of the central nervous system (CNS) often die following axonal injury (Young, 2014)
The primary interest of the present study is the expression of specific mRNA isoforms of Sox11 and Bdnf
We observed no difference in mRNA isoforms between the optic nerve crush (ONC) and the control situation, which was validated by visually inspecting genome graphs of a published ONC RNA-seq dataset (Yasuda et al, 2014)
Summary
It is well known that neurons of the peripheral nervous system (PNS) have the ability to regrow damaged axons, while neurons of the central nervous system (CNS) often die following axonal injury (Young, 2014). This difference in regenerative capacity is partly attributed to the nonpermissive growth environment of the CNS, with subsequent failure of neurons to re-myelinate their injured axons (Geisert et al, 1998; Yiu and He, 2006; Fernandes et al, 2016). Neuron-specific transcriptional cascades are involved in promoting regeneration in the PNS and in the abrogative response in the CNS.
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