Abstract
R154
Problem: While it is known that denervation of skeletal muscle can induce atrophy, the effect of denervation on muscle cell cycle genes is unclear. Further, while attempted reinnervation of laryngeal muscle has thus far been unsuccessful in restoring function, cell cycle gene expression might be utilized to predict reinnervation success. The objective of this study was to examine the effects of denervation and reinnervation of the posterior cricoarytenoid (PCA) muscle on key genes involved in the cell cycle.
Methods: Female Sprague-Dawley rats were assigned to 1 of 3 groups: control (CON, n = 24); denervation (DEN, n = 24); or reinnervation (REIN, n = 24). DEN and REIN animals had their left recurrent laryngeal nerves transected and ligated at the fourth tracheal ring while REIN animals subsequently had their nerves repaired using 10-0 suture. Animals were then euthanized after 7, 14, and 30 days, and mRNA expression examined using RT-PCR. If significant group differences were seen using one-way ANOVA (P < 0.05), Tukey post-hoc tests were employed.
Results: Expression of p21, p53, GADD45 alpha, GADD45 beta, GADD45 gamma, and cyclin D1 genes were compared. At all time points, cyclin D1 and p53 gene expressions were unchanged with DEN or REIN. However, DEN muscles were found to express significantly higher levels of p21, GADD45 alpha, and GADD45 beta than CON at all time points.
Conclusion: Interestingly, while REIN p21, GADD45 alpha, and GADD45 beta expressions were found to be elevated at 7 and 14 days, GADD45 alpha and GADD45 beta levels at 30 days were not significantly different from CON, thereby suggesting a recovery of REIN muscle gene expression at later time points.
Significance: Paradoxically, while the restoration of some cell cycle genes to normal levels in REIN muscles might be seen as an indication of successful reinnervation of the PCA, no significant functional recovery was associated.
Support: None reported.