Differential expression of glial-derived neurotrophic factor in rat laryngeal muscles during reinnervation.

Objectives/hypothesis: Nonspecific, synkinetic reinnervation is one of the causes of poor functional recovery after a peripheral nerve lesion. Knowledge of the differential expression of neurotrophic factors that subserve axon guidance, as well as neuromuscular junction formation and maintenance in the denervated muscles, may allow appropriate interventions that will improve the functional nonsynkinetic reinnervation.

Study Design: Laboratory experiment.

Methods: The expression of glial-derived neurotrophic factor (GDNF) was studied in the abductor and adductor muscles of the larynx in the rat utilizing real-time polymerase chain reaction at different times following transection, anastomosis, and reinnervation of the right recurrent laryngeal nerve (RLN). Immunostaining of GDNF, axons, and the motor endplates were performed. This data was correlated with intramuscular mRNA GDNF expression.

Results: Significant upregulation of GDNF was observed until 14 days after RLN injury. The highest level of the GDNF expression was reached at different times in posterior cricoarytenoid (PCA), lateral thyroarytenoid (LTA), and medial thyroarytenoid (MTA). These expression peaks correlated with the timing of reinnervation observed on immunohistochemistry, where PCA was reinnervated first, followed by MTA and LTA.

Conclusion: Differences of GDNF expression are linked to the differential timing of RLN axon regeneration and individual muscle reinnervation. The present finding suggests the need to further investigate the role of GDNF and other neurotrophic factors in the timing of reinnervation, axon guidance, and neuromuscular junction formation as it relates to synkinetic and nonsynkinetic RLN reinnervation. Future experimental results may provide insight to therapeutic options that could stimulate appropriate neuromuscular junction formation and nonsynkintic functional reinnervation following RLN injury.