Mice Lacking Brain-Derived Serotonin Have Altered Swallowing Function

: The intricate sensorimotor neural circuits that control swallowing are heavily reliant on serotonin (5-hydroxytryptamine [5-HT]); however, the impact of 5-HT deficiency on swallow function remains largely unexplored. We investigated this using mice deficient in tryptophan-hydroxylase-2 (TPH2), the enzyme catalyzing the rate-limiting step in 5-HT synthesis. Videofluoroscopy was utilized to characterize the swallowing function of TPH2 knockout (TPH2-/-) mice as compared with littermate controls (TPH2+/+). Results showed that 5-HT deficiency altered all 3 stages of swallowing. As compared with controls, TPH2-/- mice had significantly slower lick and swallow rates and faster esophageal transit times. Future studies with this model are necessary to determine if 5-HT replacement may rescue abnormal swallowing function. If so, supplemental 5-HT therapy may have vast applications for a large population of patients with a variety of neurologic disorders resulting in life-diminishing dysphagia, particularly amyotrophic lateral sclerosis and Parkinson's disease, for which 5-HT deficiency is implicated in the disease pathogenesis.