Videofluoroscopic Validation of a Translational Murine Model of Presbyphagia
- 699 Downloads
Presbyphagia affects approximately 40 % of otherwise healthy people over 60 years of age. Hence, it is a condition of primary aging rather than a consequence of primary disease. This distinction warrants systematic investigations to understand the causal mechanisms of aging versus disease specifically on the structure and function of the swallowing mechanism. Toward this goal, we have been studying healthy aging C57BL/6 mice (also called B6), the most popular laboratory rodent for biomedical research. The goal of this study was to validate this strain as a model of presbyphagia for translational research purposes. We tested two age groups of B6 mice: young (4–7 months; n = 16) and old (18–21 months; n = 11). Mice underwent a freely behaving videofluoroscopic swallow study (VFSS) protocol developed in our lab. VFSS videos (recorded at 30 frames per second) were analyzed frame-by-frame to quantify 15 swallow metrics. Six of the 15 swallow metrics were significantly different between young and old mice. Compared to young mice, old mice had significantly longer pharyngeal and esophageal transit times (p = 0.038 and p = 0.022, respectively), swallowed larger boluses (p = 0.032), and had a significantly higher percentage of ineffective primary esophageal swallows (p = 0.0405). In addition, lick rate was significantly slower for old mice, measured using tongue cycle rate (p = 0.0034) and jaw cycle rate (p = 0.0020). This study provides novel evidence that otherwise healthy aging B6 mice indeed develop age-related changes in swallow function resembling presbyphagia in humans. Specifically, aging B6 mice have a generally slow swallow that spans all stages of swallowing: oral, pharyngeal, and esophageal. The next step is to build upon this foundational work by exploring the responsible mechanisms of presbyphagia in B6 mice.
KeywordsDeglutition Deglutition disorders C57BL/6 C57 B6 Mouse Murine Aging Swallow Dysphagia Presbyphagia Videofluoroscopic swallow study VFSS
We graciously thank past members of the Lever Lab who contributed to preliminary data collection using non-radiographic lick rate methods (Danarae Aleman, Laura Powell, and Andries Ferreira). We also acknowledge Roderic Schlotzhauer from the University of Missouri Physics Machine Shop for design input and fabrication of the VFSS test chambers that were essential to this study. We sincerely thank Dr. Fu-Hung Hsieh’s lab at the University of Missouri Department of Bioengineering for assistance in gathering rheological data. Our highest gratitude extends to Dr. Grace Pavlath (Emory University), who facilitated our acquisition of the fluoroscope used to collect data for this study. This study was funded by NIH/NIDCD (R03DC010895, TE Lever), NIH/NINDS (R21N5084870-01, GK Pavlath), Otolaryngology – Head and Neck Surgery start-up funds (TE Lever), MU PRIME Fund (TE Lever), Mizzou Advantage (TE Lever), and the MU Center on Aging (TE Lever).
Conflict of interest
The authors declare that they have no conflict of interest.
- 3.Robbins J, Bridges AD, Taylor A. Oral, pharyngeal and esophageal motor function in aging. GI Motility online. Nature.com. London: Macmillan Publishers Limited; 2006.Google Scholar
- 24.Bureau USC: Statistical Abstract of the United States: 2012. 2012.Google Scholar
- 26.Seshamani M, Kashima M. Age-related swallowing changes. 5th ed. Philadelphia: Mosby-Elsevier; 2010.Google Scholar
- 29.Battey J, Peterson J. Model organisms for biomedical research, trans-NIH mouse initiatives. 2014.Google Scholar
- 31.Laboratory J. Genotyping protocol for SOD. 2013: from http://jaxmice.jax.org/pub-cgi/protocols/protocols.sh?objtype=protocol&protocol_id=523, 2009.
- 32.Jackson L. Genotyping protocol for SOD. 2013: from http://jaxmice.jax.org/pub-cgi/protocols/protocols.sh?objtype=protocol&protocol_id=523, 2009.
- 33.Laboratory TJ. JAX Mice Database. http://jaxmice.jax.org/strain/000664.html, 2014.
- 34.Aging NIo. Aged Rodent Colonies Handbook: Available Strains.Google Scholar
- 35.Rt B. Videofluoroscopic characterization of swallowing impairment in mouse models of amyotrophic lateral sclerosis and advanced aging. Columbia: Communication Science and Disorders: University of Missouri; 2014.Google Scholar
- 42.Lever TE, Braun SM, Brooks RT, Harris RA, Littrell LL, Neff RM, Hinkel CJ, Allen MJ, Ulsas MA. Adapting human videofluoroscopic swallow study methods to detect and characterize dysphagia in murine disease models. J Vis Exp, in press, 2014.Google Scholar
- 43.Berry RJ. The natural history of the house mouse. Field Stud. 1970;3:219–62.Google Scholar
- 46.Van Loo P, Kruitwagon C, Van Zutphen L, Koolhaas J, Baumans V. Modulation of aggression in male mice: influence of cage cleaning regime and scent markers. Anim Welf. 2000;9:281–95.Google Scholar
- 48.ADA. NDDTF: National Dysphagia Diet: Standardization for Optimal Care. Chicago: American Dietetic Association; 2002.Google Scholar
- 51.Shock LA, Gallemore BC, Hinkel CJ, Szewczyk MM, Hopewell BL, Allen MJ, Thombs LA, Lever TE. Improving the utility of laryngeal adductor reflex testing: a translational tale of mice and men. Otolaryngology, in press.Google Scholar
- 52.Agrawal A, Rengarajan S, Adler KB, Ram A, Ghosh B, Fahim M, Dickey BF. Inhibition of mucin secretion with MARCKS-related peptide improves airway obstruction in a mouse model of asthma. J Appl Physiol. 1985;102(399–405):2007.Google Scholar