title: APP overexpression prevents neuropathic pain and motoneuron death after peripheral nerve injury in mice.
abstract: Despite general capacity of peripheral nervous system to regenerate, peripheral nerve injury is often followed by incomplete recovery of function and sometimes burdened by neuropathic pain. Amyloid precursor protein (APP) was suggested to play a role in neuronal growth, however, its role in peripheral nerve repair was not studied. The aim of this study was to examine the role of APP overexpression in peripheral nerve regeneration and neuropathic pain-related behavior in mice. Sciatic nerves of APP overexpressing and FVB/N wild-type mice were transected and immediately resutured. Evaluation of motor and sensory function and autotomy was carried out during 4-week follow up. We found no autotomy behavior as well as less significant atrophy of denervated muscles in APP overexpressing animals when compared to wild-type ones. Sciatic nerve function index outcome did not differ between groups. Histological evaluation revealed that the intensity of regeneration features, including GAP-43-positive growth cones and Schwann cells number in the distal stump of the transected nerve, was also similar in both groups. However, the regenerating fibers were organized more chaotically in wild-type mice and neuromas were much more often seen in this group. The number of macrophages infiltrating the injury site was significantly higher in control group. The number of surviving motoneurons was higher in transgenic mice than in control animals. Taken together, our findings suggest that APP overexpression is beneficial for nerve regeneration processes due to better organization of regenerating fibers, increased survival of motoneurons after autotomy and prevention of neuropathic pain.
authors: Department of Child Neurology and Epileptology, The Children's Memorial Health Institute, Warsaw, Poland. k.kotulska@czd.pl
authors: Katarzyna
authors: K
authors: Kotulska
authors: Magdalena
authors: M
authors: Larysz-Brysz
authors: Marie
authors: M
authors: LePecheur
authors: Wiesław
authors: W
authors: Marcol
authors: Joanna
authors: J
authors: Lewin-Kowalik
authors: Evelyn
authors: E
authors: Paly
authors: Jacqueline
authors: J
authors: London
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D005500:Follow-Up Studies; D006801:Humans; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology*; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009416:Nerve Regeneration / Q000502:physiology; D010146:Pain / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012584:Sciatic Nerve / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D020426:Sciatic Neuropathy / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D058255:Protease Nexins; D011956:Receptors, Cell Surface