Excitatory neurons in paraventricular hypothalamus contributed to the mechanism underlying acupuncture regulating the swallowing function

Abstract

Paraventricular hypothalamus (PVH) is demonstrated to regulate stress, feeding behaviors, and other related homeostatic processes. However, no direct evidence has been investigated for the role of PVH in swallowing function. Acupuncture therapy at Lianquan (CV23) acupoint has been reported to improve the swallowing function in clinical trials, but its underlying mechanism still needs to be uncovered. Thus, we aimed to explore whether PVH involved the acupuncture mediated regulating swallowing function. Chemogenetics, electromyography (EMG) recording, and immunofluorescence staining methods were combined to demonstrate that neurons in PVH could be activated by electroacupuncture (EA) stimulation at CV23, and this neuronal cluster was represented as excitatory neurons. Furthermore, we mapped both the inputs and outputs of PVH neurons using viral tracing. The neurons in PVH projected with the brain regions, including parabrachial nucleus (PBN) and the solitary tract nucleus (NTS), which both participated in the swallowing process. The EA function regulating the swallowing was attenuated after inhibiting the neurons in PVH in the post stroke dysphagia. In conclusion, this study suggested that EA at CV23 could regulate swallowing function involving the excitatory neurons in PVH.

Electroacupuncture improves swallowing function in a post-stroke dysphagia mouse model by activating the motor cortex inputs to the nucleus tractus solitarii through the parabrachial nuclei

“…These results suggested that dysphagia could be induced by photothrombotic ischemia in the M1, and thus proved the successful establishment of the PSD mouse model. These observations were consistent with our previous results 43 – 45 , which indicated that focal ischemia in the M1 can induce impaired EMG responses in the mylohyoid and decreased water consumption in mice. Next, to determine whether EA-CV23 attenuated the swallowing difficulty in PSD model mice, EMG recordings in the mylohyoid and the water consumption test were performed 24 h following EA-CV23.…”

“…The mice were placed in an anesthesia induction box containing 4% isoflurane in an oxygen/air mixture until anesthetized, and then transferred to an anesthetic mask to maintain anesthesia with 2% isoflurane provided by an animal anesthesia machine (R500, RWD, China). Then the tail was soaked in warm water at 38 ± 2°C to expand the tail vein, and the tail vein was injected with 15 mg/ml RB solution (diluted with 0.9% saline, Sigma, USA) as previously described 45 , 79 . The coordinates of the M1 (AP: −0.12 mm, ML: −1.03 mm) and PFC (AP: −0.3 mm, ML: −1.75 mm) were selected based on the PRV labeling regions and the Paxinos and Franklin Mouse Brain Atlas (second edition).…”

Role of TRPV1 in electroacupuncture‐mediated signal to the primary sensory cortex during regulation of the swallowing function

“…Previous investigations have reported that neural activity in the primary motor cortex (M1) was enhanced by EA‐CV23 in PSD mice. 8 , 9 , 10 , 11 When acupuncture is delivered to acupoints, the cortex is activated. 12 , 13 Nevertheless, the pathway of EA signals transmitting to M1 remains unclear.…”

“…However, the mechanism of the EA's effect is still in the exploration. Previous investigations have reported that neural activity in the primary motor cortex (M1) was enhanced by EA‐CV23 in PSD mice 8‐11 . When acupuncture is delivered to acupoints, the cortex is activated 12,13 .…”

Acupuncture for swallowing disorder after recovery from COVID-19: A protocol for systematic review and meta analysis

“…[11] Combined with chemical genetics, electromyography recording, and immunofluorescence staining, it has been shown that electroacupuncture stimulation of acupoint lianquan can activate paraventricular hypothalamus neurons and regulate human swallowing function. [12] Thus, acupuncture can significantly improve the swallowing function of patients with swallowing disorder, with quick effects, few adverse reactions, convenient operation, low cost, and diversity of therapy. [13][14][15][16] During the epidemic of COVID-19, acupuncture has been used as a supplementary treatment of COVID-19 in China, and its curative effect has been proved by research.…”