Neurotrophic factor BDNF is upregulated in soft palate muscles of snorers and sleep apnea patients

Farhan Shah; Sture Forsgren; Thorbjörn Holmlund; Eva Levring Jäghagen; Diana Berggren; Karl A Franklin; Per Stål

doi:10.1002/lio2.225

Neurotrophic factor BDNF is upregulated in soft palate muscles of snorers and sleep apnea patients

Laryngoscope Investig Otolaryngol. 2018 Nov 28;4(1):174-180. doi: 10.1002/lio2.225. eCollection 2019 Feb.

Authors

Farhan Shah¹, Sture Forsgren¹, Thorbjörn Holmlund², Eva Levring Jäghagen³, Diana Berggren², Karl A Franklin⁴, Per Stål¹

Affiliations

¹ Department of Integrative Medical Biology Umeå University Umeå Sweden.
² Laboratory of Muscle Biology, the Department of Clinical Sciences, Otolaryngology Umeå University Umeå Sweden.
³ Department of Odontology, Oral, and Maxillofacial Radiology Umeå University Umeå Sweden.
⁴ Department of Surgical and Perioperative Sciences Umeå University Umeå Sweden.

Abstract

Objectives: Neuromuscular injuries are suggested to contribute to upper airway collapse and swallowing dysfunction in patients with sleep apnea. Neurotrophins, a family of proteins involved in survival, development, and function of neurons, are reported to be upregulated in limb muscle fibers in response to overload and nerve damage. We aimed to investigate the expression of two important neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in muscle fibers of uvula from snorers and sleep apnea patients and to compare these findings with pharyngeal function.

Methods: Uvula muscle biopsies from 22 patients and 10 controls were analyzed for BDNF, NGF, and cytoskeletal protein desmin using immunohistochemistry. Pharyngeal swallowing function was assessed using videoradiography.

Results: BDNF, but not NGF, was significantly upregulated in a subpopulation of muscle fibers in snoring and sleep apnea patients. Two major immunoreaction patterns for BDNF were observed; a fine grainy point like BDNF staining was displayed in muscle fibers of both patients and controls (41 ± 23 vs. 25 ± 17%, respectively, P = .06), while an abnormal upregulated intense-dotted or disorganized reaction was mainly observed in patients (8 ± 8 vs. 2 ± 2%, P = .02). The latter fibers, which often displayed an abnormal immunoreaction for desmin, were more frequent in patients with than without swallowing dysfunction (10 ± 8 vs. 3 ± 3%, P = .05).

Conclusion: BDNF is upregulated in the upper airway muscles of snorers and sleep apnea patients, and especially in patients with swallowing dysfunction. Upregulation of BDNF is suggested to be a response to denervation, reinnervation, and repair of injured muscle fibers. Our findings propose that damaged upper airway muscles might heal following treatment for snoring and sleep apnea.

Level of evidence: NA.

Keywords: Neurotrophins; OSA; brain‐derived neurotrophic factor (BDNF); desmin; muscle fiber; nerve; nerve‐derived neurotrophic factor (NGF); neuromuscular injury; obstructive sleep apnea; snorers; swallowing dysfunction.