C3 exoenzyme lacks effects on peripheral axon regeneration in vivo
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C3 exoenzyme lacks effects on peripheral axon regeneration in vivo. / Auer, Maria; Allodi, Ilary; Barham, Mohammed; Udina, Esther; Neiss, Wolfram F; Navarro, Xavier; Klimaschewski, Lars.
In: Journal of the Peripheral Nervous System Online, Vol. 18, No. 1, 2013, p. 30-36.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - C3 exoenzyme lacks effects on peripheral axon regeneration in vivo
AU - Auer, Maria
AU - Allodi, Ilary
AU - Barham, Mohammed
AU - Udina, Esther
AU - Neiss, Wolfram F
AU - Navarro, Xavier
AU - Klimaschewski, Lars
N1 - © 2013 Peripheral Nerve Society.
PY - 2013
Y1 - 2013
N2 - Peripheral nerve injury triggers the activation of the small GTPase RhoA in spinal motor and peripheral sensory neurons. C3 transferase, an exoenzyme produced by Clostridium botulinum that inactivates RhoA by ADP-ribosylation, has been successfully applied in central nervous system (CNS) lesion models to facilitate regeneration functionally and morphologically. Until now it has not been demonstrated if C3bot exerts positive effects on peripheral axon regeneration as well. In organotypic spinal cord preparations, C3bot reduced axonal growth of motoneurons, while no effect on sensory axon outgrowth from dorsal root ganglia (DRG) explants was observed. Enzymatically inactive C3E174Q was ineffective in both culture models. Spinal cord slices exhibited a significant increase in microglia/macrophages after treatment with C3bot suggesting an inflammatory component in the inhibition of axon growth. C3bot or C3E174Q were then applied into conduits implanted after transection of the sciatic nerve in rats. Functional evaluation by electrophysiology, nociception, and walking track tests did not show any significant difference between groups with active or mutant C3E174Q . Transmission electron microscopy of the regenerated nerves revealed no significant differences in the number of myelinated and unmyelinated axons 6 weeks after surgery. Compared to the CNS, the functional significance of RhoA may be limited during nerve regeneration in a growth-promoting environment.
AB - Peripheral nerve injury triggers the activation of the small GTPase RhoA in spinal motor and peripheral sensory neurons. C3 transferase, an exoenzyme produced by Clostridium botulinum that inactivates RhoA by ADP-ribosylation, has been successfully applied in central nervous system (CNS) lesion models to facilitate regeneration functionally and morphologically. Until now it has not been demonstrated if C3bot exerts positive effects on peripheral axon regeneration as well. In organotypic spinal cord preparations, C3bot reduced axonal growth of motoneurons, while no effect on sensory axon outgrowth from dorsal root ganglia (DRG) explants was observed. Enzymatically inactive C3E174Q was ineffective in both culture models. Spinal cord slices exhibited a significant increase in microglia/macrophages after treatment with C3bot suggesting an inflammatory component in the inhibition of axon growth. C3bot or C3E174Q were then applied into conduits implanted after transection of the sciatic nerve in rats. Functional evaluation by electrophysiology, nociception, and walking track tests did not show any significant difference between groups with active or mutant C3E174Q . Transmission electron microscopy of the regenerated nerves revealed no significant differences in the number of myelinated and unmyelinated axons 6 weeks after surgery. Compared to the CNS, the functional significance of RhoA may be limited during nerve regeneration in a growth-promoting environment.
KW - ADP Ribose Transferases/genetics
KW - Animals
KW - Animals, Newborn
KW - Axotomy
KW - Botulinum Toxins/genetics
KW - Disease Models, Animal
KW - Female
KW - Ganglia, Spinal/cytology
KW - Mutation/genetics
KW - Nerve Regeneration/drug effects
KW - Organ Culture Techniques
KW - Rats
KW - Rats, Sprague-Dawley
KW - Sciatic Nerve/pathology
KW - Sciatic Neuropathy/drug therapy
KW - Spinal Cord/cytology
KW - Time Factors
U2 - 10.1111/jns5.12004
DO - 10.1111/jns5.12004
M3 - Journal article
C2 - 23521641
VL - 18
SP - 30
EP - 36
JO - Journal of the Peripheral Nervous System
JF - Journal of the Peripheral Nervous System
SN - 1529-8027
IS - 1
ER -
ID: 227433731