Effects of menthol on swallowing function in a mouse model of presbyphagia

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] The goal of this study was to characterize the progression of presbyphagia in our recently established mouse model and investigate the treatment effect of menthol on swallow dysfunction in advanced aging mice. To accomplish these goals, we evaluated a total of 17 advanced-age (i.e., late senescent) C57BL/6 mice (22-25 months; 9 males, 8 females) using our freely-behaving videofluoroscopic swallow study (VFSS) protocol. Three test solutions were administered at room temperature in the following order, spaced 30 minutes apart: standard VFSS recipe, standard VFSS recipe + 5 mM menthol, and standard VFSS recipe. Video recordings were analyzed to quantify the immediate and potentiation (30 minute) effects of menthol. Swallow function in late senescent mice was significantly more impaired than young mice. Oral ingestion of 5 mM menthol had immediate and potentiation effects on all three stages of swallowing. Specifically, menthol resulted in significantly (p<0.05) faster lick rates, higher lick-swallow ratios, longer inter-swallow intervals, slower swallow rates, faster esophageal transit times, higher proportion of effective esophageal swallows, and fewer swallows required to clear the esophagus. This study provides novel evidence that menthol "rescues" swallow function, returning it to youthful levels. A larger scale pre-clinical study is underway to systematically investigate the therapeutic efficacy and safety of menthol as a treatment strategy for presbyphagia/dysphagia in mice and to elucidate the responsible molecular mechanisms of action.