Impaired regeneration of bcl-2-lacking peripheral nerves.
OBJECTIVE
The outcome of peripheral nerve damage in still not satisfactory, despite the general capacity of peripheral nervous system to regenerate. The molecular mechanisms underlying nerve regeneration are still not clear, but it is likely that apoptosis regulating genes plays a crucial role in these processes. The aim of the present study was to establish the role of the anti-apoptotic gene bcl-2 in peripheral nerve repair.


METHODS
Sciatic nerves of bcl-2-deficient and wild type mice were transected, and immediately re-sutured. The regeneration was assessed functionally and morphologically throughout the 4-week follow-up.


RESULTS
We found markedly worse sciatic function index outcome, as well as more significant atrophy of denervated muscles in bcl-2 knock-out animals when compared with wild-type ones. The intensity of histological regeneration features, including GAP-43-positive growth cones, Schwann cells and macrophages in the distal stump of the transected nerve, was also decreased. The number of motor and sensory neurons in the relevant cross-sections of spinal cord was similar in both groups of mice.


CONCLUSIONS
We concluded that the bcl-2 gene plays an important role in peripheral nerve regeneration, influencing nerve injury site clearing, fiber regrowth and myelination.
Kotulska
Katarzyna
K
Department of Neurology and Epileptology, The Children's Memorial Health Institute, Warsaw, Poland.
Marcol
Wiesław
W
Larysz-Brysz
Magdalena
M
Barski
Jarosław Jerzy
JJ
Fus
Zbigniew
Z
Lewin-Kowalik
Joanna
J
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D019771:Axotomy; D019922:GAP-43 Protein / Q000032:analysis; D019254:Genes, bcl-2; D020439:Growth Cones / Q000737:chemistry / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000473:pathology; D009121:Muscle Denervation; D009133:Muscular Atrophy / Q000209:etiology; D009186:Myelin Sheath / Q000502:physiology; D009416:Nerve Regeneration / Q000235:genetics* / Q000502:physiology; D009475:Neurons, Afferent / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency / Q000502:physiology*; D009418:S100 Proteins / Q000032:analysis; D012583:Schwann Cells / Q000473:pathology; D012584:Sciatic Nerve / Q000293:injuries / Q000473:pathology / Q000502:physiology*; D013116:Spinal Cord / Q000473:pathology
D019922:GAP-43 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D009418:S100 Proteins