Mice Lacking Brain-Derived Serotonin Have Altered Swallowing Function

Abstract

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.

Keywords: 5-hydroxytryptamine (5-HT); amyotrophic lateral sclerosis (ALS); mouse model; serotonin deficiency; tryptophan hydroxylase (TPH); videofluoroscopy.

Figure 1.

Videofluoroscopic images of a mouse drinking contrast solution (asterisk). A bolus (red arrow) is tracked through the (A, B) oropharyngeal and (C, D) esophageal stages of swallowing. UES, upper esophageal sphincter.

Figure 2.

5-Hydroxytryptamine deficiency affected all 3 stages of swallowing. Lick rate was impaired earlier for TPH2^−/− males. *P <.05. **P <.01. ***P ≤ .001. ns, nonsignificant; TPH2, tryptophan-hydroxylase-2. Error bars indicate standard error.