Expression of Regeneration‐Associated Proteins in Primary Sensory Neurons and Regenerating Axons After Nerve Injury—An Overview

Abstract

Peripheral nerve injury results in profound alterations of the affected neurons resulting from the interplay between intrinsic and extrinsic molecular events. Restarting the neuronal regenerative program is an important prerequisite for functional recovery of the injured peripheral nerve. The primary sensory neurons with their cell bodies in the dorsal root ganglia provide a useful in vivo and in vitro model for studying the mechanisms that regulate intrinsic neuronal regeneration capacity following axotomy. These studies frequently need to indicate the regenerative status of the corresponding neurons. We summarize the critical issues regarding immunohistochemical detection of several regeneration-associated proteins as markers for the initiation of the regeneration program in rat primary sensory neurons and indicators of axon regeneration in the peripheral nerves. This overview also includes our own results of GAP43 and SCG10 expression in different DRG neurons following double immunostaining with molecular markers of neuronal subpopulations (NF200, CGRP, and IB4) as well as transcription factors (ATF3 and activated STAT3) following unilateral sciatic nerve injury. Anat Rec, 301:1618-1627, 2018. © 2018 Wiley Periodicals, Inc.

Collapsin Response Mediator Protein 4 (CRMP4) Facilitates Wallerian Degeneration and Axon Regeneration following Sciatic Nerve Injury

“…To test the cell-autonomous contribution of CRMP4 to the regrowth of damaged axons, we measure the extent of regeneration of axotomized DRG neurons in vitro. DRGs were isolated from E15-16 wildtype or Crmp4 À/À mouse embryos, and the dissociated neurons were plated in microfluidic devices for 4 d until the axons projected into the axonal compartment (Jones et al, 2006;Frey et al, 2015;Dubovy¨et al, 2018). Axotomy was then performed by increasing the flow of medium in the axonal compartment to shear the axons, and the damaged neurons were left to regenerate for 24 h. Following axotomy, Crmp4 À/À DRG neurons regrew significantly worse than their wild-type counterparts, exhibiting 43% less regrowth (Fig.…”

miR‐22‐3p enhances the intrinsic regenerative abilities of primary sensory neurons via the CBL/p‐EGFR/p‐STAT3/GAP43/p‐GAP43 axis

“…EGF and EGFR show neurotrophic and protective functions and promote axon growth and synapse formation (Flynn et al, ; Gibson & Tolbert, ; Hermann et al, ; Iwakura et al, ; Peng et al, ). However, GAP43 is a key protein that regulates the intrinsic neurite regenerative ability of neurons that is expressed at a low level in adult primary sensory neurons (Dubovy, Klusakova, Hradilova‐Svizenska, & Joukal, ; Qiao, Cong, Li, Li, & Li, ). The expression of EGFR in neurons peaks at birth and then decreases during development (Berry, Ahmed, Douglas, & Logan, ).…”

“…However, GAP43 is a key protein that regulates the intrinsic neurite regenerative ability of neurons that is expressed at a low level in adult primary sensory neurons (Dubovy, Klusakova, Hradilova-Svizenska, & Joukal, 2018;Qiao, Cong, Li, Li, & Li, 2018). The expression of EGFR in neurons peaks at birth and then decreases during development (Berry, Ahmed, Douglas, & Logan, 2011).…”

Introduction: Thematic Papers Issue on Peripheral Nerve Regeneration and Repair

“…Reactivation of the neuronal growth program is one of the most important conditions for successful regeneration of the lesioned axons in injured peripheral nerves (Allodi et al, ; Doron‐Mandel et al, ). The review article presented by Dubový and colleagues, from Masaryk University in Brno, critically summarizes recent knowledge regarding the expression of regeneration‐associated proteins to be used as markers for the initiation and progress of the regeneration program in primary sensory neurons as well as indicators of axon regeneration in rodent peripheral nerves (Dubový et al, , this issue). Particular focus was placed in the variable expression of GAP43 and SGC10 as markers of regenerating axons, and the induction of transcription factors ATF3 and STAT3.…”