Differences in peripheral nerve degeneration/regeneration between wild-type and neuronal nitric oxide synthase knockout mice.
Nitric oxide (NO), a unique biological messenger molecule, is synthesized by three isoforms of the enzyme NO synthase (NOS) and diffuses from the site of production across cellular membranes. A postulated role for NO in degeneration and regeneration of peripheral nerves has been explored in a sciatic nerve model comparing wild-type mice and mice lacking neuronal NOS after transection and microsurgical repair. In NOS knockout mice, regenerative delay was observed, preceded by a decelerated Wallerian degeneration (WD). In the regenerated nerve, pruning of uncontrolled sprouts was disturbed, leading to an enhanced number of axons, whereas remyelination seemed to be less affected. Delayed regeneration was associated with a delayed recovery of sensor and motor function. In such a context, possible NO targets are neurofilaments and myelin sheaths of the interrupted axon, filopodia of the growth cone, newly formed neuromuscular endplates, and Schwann cells in the distal nerve stump. The results presented suggest that 1) local release of NO following peripheral nerve injury is a crucial factor in degeneration/regeneration, 2) success of fiber regeneration in the peripheral nervous system depends on a regular WD, and 3) manipulation of NO supply may offer interesting therapeutic options for treatment of peripheral nerve lesions.
Keilhoff
Gerburg
G
Institute of Medical Neurobiology, Medical Faculty, Otto-von-Guericke-University, Magdeburg, Germany. gerburg.keilhoff@medizin.uni-magdeburg.de
Fansa
Hisham
H
Wolf
Gerald
G
D000818:Animals; D001369:Axons / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000201:enzymology; D009416:Nerve Regeneration / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D020426:Sciatic Neuropathy / Q000188:drug therapy
D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse