NTF4
Neurotrophin-4 precursor (NT-4) (Neurotrophin-5) (NT-5) (Neutrophic factor 4) [NTF5]
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Laryngeal dysfunction in the elderly is a major cause of disability, from voice disorders to dysphagia and loss of airway protective reflexes. Few, if any, therapies exist that target age-related laryngeal muscle dysfunction. Neurotrophins are involved in muscle innervation and differentiation of neuromuscular junctions (NMJs). It is thought that neurotrophins enhance neuromuscular transmission by increasing neurotransmitter release. The neuromuscular junctions (NMJs) become smaller and less abundant in aging rat laryngeal muscles, with evidence of functional denervation. We explored the effects of NTF4 for future clinical use as a therapeutic to improve function in aging human laryngeal muscles. Here, we provide the detailed protocol for systemic application and direct injection of NTF4 to investigate the ability of aging rat laryngeal muscle to remodel in response to NTF4 application. In this method, rats either received NTF4 either systemically via osmotic pump or by direct injection through the vocal folds. Laryngeal muscles were then dissected and used for histological examination of morphology and age-related denervation.
MeSH Terms
- Aging
- Animals
- Humans
- Infusion Pumps, Implantable
- Infusions, Subcutaneous
- Injections, Intramuscular
- Laryngeal Muscles
- Nerve Growth Factors
- Neuromuscular Junction
- Rats, Inbred F344
- Synaptic Transmission
- Vocal Cord Dysfunction
Clinical evidence suggests that laryngeal muscle dysfunction is associated with human aging. Studies in animal models have reported morphological changes consistent with denervation in laryngeal muscles with age. Life-long laryngeal muscle activity relies on cytoskeletal integrity and nerve-muscle communication at the neuromuscular junction (NMJ). It is thought that neurotrophins enhance neuromuscular transmission by increasing neurotransmitter release. We hypothesized that treatment with neurotrophin 4 (NTF4) would modify the morphology and functional innervation of aging rat laryngeal muscles. Fifty-six Fischer 344xBrown Norway rats (6- and 30-mo age groups) were used to evaluate to determine if NTF4, given systemically (n = 32) or directly (n = 24), would improve the morphology and functional innervation of aging rat thyroarytenoid muscles. Results demonstrate the ability of rat laryngeal muscles to remodel in response to neurotrophin application. Changes were demonstrated in fiber size, glycolytic capacity, mitochondrial, tyrosine kinase receptors (Trk), NMJ content, and denervation in aging rat thyroarytenoid muscles. This study suggests that growth factors may have therapeutic potential to ameliorate aging-related laryngeal muscle dysfunction.
MeSH Terms
- Aging
- Animals
- Intercellular Signaling Peptides and Proteins
- Laryngeal Muscles
- Nerve Growth Factors
- Rats
- Rats, Inbred BN
- Rats, Inbred F344
- Treatment Outcome
Keywords
- Growth factors
- NTF4
- larynx
- muscle
- neurotrophic