title: Acute exposure to vibration is an apoptosis-inducing stimulus in the vocal fold epithelium.
abstract: Clinical voice disorders pose significant communication-related challenges to patients. The purpose of this study was to quantify the rate of apoptosis and tumor necrosis factor-alpha (TNF-α) signaling in vocal fold epithelial cells in response to increasing time-doses and cycle-doses of vibration. 20 New Zealand white breeder rabbits were randomized to three groups of time-doses of vibration exposure (30, 60, 120min) or a control group (120min of vocal fold adduction and abduction). Estimated cycle-doses of vocal fold vibration were extrapolated based on mean fundamental frequency. Laryngeal tissue specimens were evaluated for apoptosis and gene transcript and protein levels of TNF-α. Results revealed that terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was significantly higher after 120min of vibration compared to the control. Transmission electron microscopy (TEM) revealed no significant effect of time-dose on the mean area of epithelial cell nuclei. Extrapolated cycle-doses of vibration exposure were closely related to experimental time-dose conditions, although no significant correlations were observed with TUNEL staining or mean area of epithelial cell nuclei. TUNEL staining was positively correlated with TNF-α protein expression. Our findings suggest that apoptosis can be induced in the vocal fold epithelium after 120min of modal intensity phonation. In contrast, shorter durations of vibration exposure do not result in apoptosis signaling. However, morphological features of apoptosis are not observed using TEM. Future studies are necessary to examine the contribution of abnormal apoptosis to vocal fold diseases.
authors: Department of Hearing and Speech Sciences, Vanderbilt University School of Medicine, 1215 21st Avenue South, Nashville, TN 37232, USA. Electronic address: cnovaleski@monell.org.
authors: Carolyn K
authors: CK
authors: Novaleski
authors: Department of Hearing and Speech Sciences, Vanderbilt University School of Medicine, 1215 21st Avenue South, Nashville, TN 37232, USA. Electronic address: emily.e.kimball@vanderbilt.edu.
authors: Emily E
authors: EE
authors: Kimball
authors: Department of Otolaryngology, Vanderbilt University School of Medicine, 1215 21st Avenue South, Nashville, TN 37232, USA. Electronic address: m_mizuta@ent.kuhp.kyoto-u.ac.jp.
authors: Masanobu
authors: M
authors: Mizuta
authors: Department of Hearing and Speech Sciences, Vanderbilt University School of Medicine, 1215 21st Avenue South, Nashville, TN 37232, USA; Department of Otolaryngology, Vanderbilt University School of Medicine, 1215 21st Avenue South, Nashville, TN 37232, USA; Department of Mechanical Engineering, Vanderbilt University, 101 Olin Hall, Nashville, TN 37235, USA. Electronic address: bernard.rousseau@vanderbilt.edu.
authors: Bernard
authors: B
authors: Rousseau
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D004195:Disease Models, Animal; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D011817:Rabbits; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D014732:Vibration; D014827:Vocal Cords / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D014832:Voice Disorders / Q000235:genetics* / Q000473:pathology
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: Apoptosis; Epithelium; Terminal deoxynucleotidyl transferase dUTP nick end labeling; Transmission electron microscopy; Tumor necrosis factor‐alpha; Vocal fold