This study adapted human videofluoroscopic swallowing study (VFSS) methods for use with murine disease models for the purpose of facilitating translational dysphagia research. Successful outcomes are dependent upon three critical components: test chambers that permit self-feeding while standing unrestrained in a confined space, recipes that mask the aversive taste/odor of commercially-available oral contrast agents, and a step-by-step test protocol that permits quantification of swallow physiology. Elimination of one or more of these components will have a detrimental impact on the study results. Moreover, the energy level capability of the fluoroscopy system will determine which swallow parameters can be investigated. Most research centers have high energy fluoroscopes designed for use with people and larger animals, which results in exceptionally poor image quality when testing mice and other small rodents. Despite this limitation, we have identified seven VFSS parameters that are consistently quantifiable in mice when using a high energy fluoroscope in combination with the new murine VFSS protocol. We recently obtained a low energy fluoroscopy system with exceptionally high imaging resolution and magnification capabilities that was designed for use with mice and other small rodents. Preliminary work using this new system, in combination with the new murine VFSS protocol, has identified 13 swallow parameters that are consistently quantifiable in mice, which is nearly double the number obtained using conventional (i.e., high energy) fluoroscopes. Identification of additional swallow parameters is expected as we optimize the capabilities of this new system. Results thus far demonstrate the utility of using a low energy fluoroscopy system to detect and quantify subtle changes in swallow physiology that may otherwise be overlooked when using high energy fluoroscopes to investigate murine disease models.

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.

The goal of this study was to compare dysphagia phenotypes in low and high copy number (LCN and HCN) transgenic superoxide dismutase 1 (SOD1) mouse models of ALS to accelerate the discovery of novel and effective treatments for dysphagia and early amyotrophic lateral sclerosis (ALS) diagnosis. Clinicopathological features of dysphagia were characterized in individual transgenic mice and age-matched controls utilizing videofluoroscopy in conjunction with postmortem assays of the tongue and hypoglossal nucleus. Quantitative PCR accurately differentiated HCN-SOD1 and LCN-SOD1 mice and nontransgenic controls. All HCN-SOD1 mice developed stereotypical paralysis in both hindlimbs. In contrast, LCN-SOD1 mice displayed wide variability in fore-and hindlimb involvement. Lick rate, swallow rate, inter-swallow interval, and pharyngeal transit time were significantly altered in both HCN-SOD1 and LCN-SOD1 mice compared to controls. Tongue weight, tongue dorsum surface area, total tongue length, and caudal tongue length were significantly reduced only in the LCN-SOD1 mice compared to age-matched controls. LCN-SOD1 mice with lower body weights had smaller/lighter weight tongues, and those with forelimb paralysis and slower lick rates died at a younger age. LCN-SOD1 mice had a 32% loss of hypoglossal neurons, which differed significantly when compared to age-matched control mice. These novel findings for LCN-SOD1 mice are congruent with reported dysphagia and associated tongue atrophy and hypoglossal nucleus pathology in human ALS patients, thus highlighting the translational potential of this mouse model in ALS research.

It is not uncommon for sedentary individuals to cite leg fatigue as the primary factor for test termination during a cardiopulmonary exercise test (CPET) on a cycle ergometer. The purpose of this study was to examine the effect of 2 weeks of lower body resistance training (RT) on cardiopulmonary capacity in sedentary middle-aged females. Additionally, the impact of RT on muscle strength was evaluated. Following familiarization, 28 women (18 exercise group, 10 control group) completed a maximal CPET on a cycle ergometer to determine peak oxygen uptake and leg extensor strength assessed using isokinetic dynamometry. Participants in the exercise group performed 2 weeks (6 sessions) of lower body RT, which comprised leg press, leg curl, and leg extension exercises. A 2-way repeated-measures ANOVA was used to evaluate the difference in changes of peak oxygen uptake and peak torque (PT). Peak oxygen uptake significantly improved from 22.2 ± 4.5 mL·kg−1·min−1 to 24.3 ± 4.4 mL·kg−1·min−1 (10.8%, p < 0.05) as well as PT from 83.1 ± 25.4 Nm to 89.0 ± 29.7 Nm (6.1%, p < 0.05) in the exercise group with no change in the control group. These findings provide initial evidence that 2 weeks of lower body RT prior to a CPET may be a helpful preconditioning strategy to achieve a more accurate peak oxygen uptake during testing, enhancing tolerability to a CPET by improving lower body strength.

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