2,4-Dinitrophenol blocks neurodegeneration and preserves sciatic nerve function after trauma.
Preventing the harm caused by nerve degeneration is a major challenge in neurodegenerative diseases and in various forms of trauma to the nervous system. The aim of the current work was to investigate the effects of systemic administration of 2,4-dinitrophenol (DNP), a compound with newly recognized neuroprotective properties, on sciatic-nerve degeneration following a crush injury. Sciatic-nerve injury was induced by unilateral application of an aneurysm clip. Four groups of mice were used: uninjured, injured treated with vehicle (PBS), injured treated with two intraperitoneal doses of DNP (0.06 mg DNP/kg every 24 h), and injured treated with four doses of DNP (every 12 h). Animals were sacrificed 48 h post injury and both injured and uninjured (contralateral) sciatic nerves were processed for light and electron microscopy. Morphometric, ultrastructural, and immunohistochemical analysis of injured nerves established that DNP prevented axonal degeneration, blocked cytoskeletal disintegration, and preserved the immunoreactivity of amyloid precursor protein (APP) and Neuregulin 1 (Nrg1), proteins implicated in neuronal survival and myelination. Functional tests revealed preservation of limb function following injury in DNP-treated animals. Results indicate that DNP prevents nerve degeneration and suggest that it may be a useful small-molecule adjuvant in the development of novel therapeutic approaches in nerve injury.
da Costa
Rodrigo F Madeiro
RF
Programa de Bioquimica e Biofisica Celular, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Martinez
Ana M Blanco
AM
Ferreira
Sergio T
ST
D019297:2,4-Dinitrophenol / Q000494:pharmacology* / Q000627:therapeutic use; D016564:Amyloid beta-Protein Precursor / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D051379:Mice; D020890:Neuregulin-1 / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D020426:Sciatic Neuropathy / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D014855:Wallerian Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control
D016564:Amyloid beta-Protein Precursor; D020890:Neuregulin-1; D018696:Neuroprotective Agents; D019297:2,4-Dinitrophenol