Nerve-terminal and Schwann-cell response after nerve injury in the absence of nitric oxide.
Dystrophic muscles show alterations in the dystrophin-glycoprotein complex and a lack of neuronal nitric oxide (NO) synthase. In mdx mice, presynaptic expression of neuronal NO synthase is decreased, suggesting that presynaptic signaling may be altered in dystrophic muscle. In this study, we examined the nerve-terminal and Schwann-cell responses after a crush lesion in control and NO-deficient mice. Seven days after nerve crush, 24% of control neuromuscular junctions (n = 200) showed ultraterminal sprouts, whereas in NO-deficient mice this frequency was 28.5% (n = 217; P > 0.05 compared to controls; chi-square test). Schwann-cell response did not change in the absence of NO, after a nerve lesion of 7-day duration. Fourteen days after the lesion, nerve terminals sprouted and Schwann cells showed an extensive network of processes away from the synaptic site in controls. In the absence of NO, there was a dramatic decrease in nerve-terminal sprouting and Schwann-cell processes failed to extend away from the endplate. These results show that NO is involved in the nerve-terminal and Schwann-cell response to nerve injury. They also suggest that presynaptic molecular signaling may be impaired in dystrophic muscles, and this could influence the innervation and survival of newly formed myofibers generated by cell-mediated therapies.
Marques
Maria Julia
MJ
Department of Anatomy, Institute of Biology, State University of Campinas (Unicamp), Campinas, SP 13083-970, Brazil. marques@unicamp.br
Pereira
Elaine Cristina Leite
EC
Minatel
Elaine
E
Neto
Humberto Santo
HS
D000818:Animals; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009409:Nerve Crush; D009411:Nerve Endings / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D009929:Organ Size / Q000502:physiology; D059348:Peripheral Nerve Injuries; D012583:Schwann Cells / Q000502:physiology*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D019331:NG-Nitroarginine Methyl Ester