Electroacupuncture Modulates 5-HT4R-Mediated cAMP/PKA Signaling to Improve Intestinal Motility Disorders in a Thy1-αSyn Parkinson’s Mouse Model

Abstract

Constipation is one of the most common nonmotor symptoms in patients with Parkinson’s disease (PD) and often occurs before motor symptoms. Electroacupuncture effectively improves the symptoms of constipation in patients with PD. In the present study, we used thymus cell antigen 1-α-synuclein (Thy1-αSyn) transgenic mice as a model of intestinal motility disorders in PD to determine the therapeutic effect of electroacupuncture and the underlying mechanisms. Electroacupuncture significantly improved fecal excretion and accelerated the rate of small-intestinal propulsion in Thy1-αSyn mice by upregulating the serotonin concentration and the expression of the serotonin 4 receptor. Consequently, the downstream cyclic AMP/protein kinase A (cAMP/PKA) pathway was affected, and to upregulate and downregulate, the expression of substance P was upregulated, and the expression of calcitonin gene-related peptide was downregulated. In summary, electroacupuncture improved intestinal motility in PD mice by affecting serotonin levels, serotonin 4 receptor expression, and the cAMP/PKA pathway, providing a potentially effective and promising complementary and alternative therapy for relieving constipation symptoms in patients with PD.

Acupuncture for constipation in Parkinson’s disease: A systematic review and meta-analysis of randomized controlled trials

“…By upregulating 5-HT and 5-HT4R in colon tissue, electroacupuncture can activate the downstream cAMP/PKA pathway, regulate the expression of related neurotransmitters SP and CGRP, and then regulate the intestinal nervous system and improve intestinal movement disorders, thereby relieving constipation in PD. [51] Evidence has found that acupuncture can treat functional constipation by promoting gastrointestinal peristalsis, regulating hormones in the peripheral gastrointestinal tract, and maintaining a balance between excitatory and inhibitory neurons in the Enteric Nervous System. [52–54]…”

“…By upregulating 5-HT and 5-HT4R in colon tissue, electroacupuncture can activate the downstream cAMP/PKA pathway, regulate the expression of related neurotransmitters SP and CGRP, and then regulate the intestinal nervous system and improve intestinal movement disorders, thereby relieving constipation in PD. [51] Evidence has found that acupuncture can treat functional constipation by promoting gastrointestinal peristalsis, regulating hormones in the peripheral gastrointestinal tract, and maintaining a balance between excitatory and inhibitory neurons in the Enteric Nervous System. [52][53][54] The results of the meta-analysis of 11 RCTs showed that acupuncture combined with conventional treatment could assist in alleviating the constipation of PD patients, effectively increase the number of spontaneous defecations, improve quality of life, increase rectal resting pressure, and lessen the severity of chronic constipation.…”