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Molecular and Neural Mechanisms of Swallowing
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Molecular and Neural Mechanisms of Swallowing

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 May 2020) | Viewed by 21895

Special Issue Editors

Prof. Dr. Junichi Kitagawa

E-Mail Website
Guest Editor
Department of Oral Physiology, School of Dentistry, Matsumoto Dental University, 1780 Gobara Hirooka, Shiojiri, Nagano 399-0781, Japan
Interests: neurophysiology of swallowing; neuropathic orofacial pain; oral physiology; oral neuroscience; functional food for dysphagia; neuron-glia interaction
Dr. Mohammad Zakir Hossain

E-Mail Website
Co-Guest Editor
Department of Oral Physiology, School of Dentistry, Matsumoto Dental University, 1780 Gobara Hirooka, Shiojiri, Nagano 399-0781, Japan
Interests: Swallowing; Mastication; Orofacial pain; Oral physiology

Special Issue Information

Dear Colleagues,

Swallowing is a complex motor function. Although a brainstem swallowing central pattern generator has been well established, the cellular and molecular mechanisms that control swallowing are not fully understood. Besides, neuromodulation mechanisms at the peripheral and central neural circuits, the neurotransmitter system, coordination of swallowing with other motor activities (e.g., respiration, mastication), and the influence and mechanisms of integrating peripheral sensory perception (e.g., taste, olfaction, pain) are not fully elucidated.

Additionally, sensory inputs from swallowing-related regions are vital for different phases of swallowing. Reduced sensory input from the periphery is one of the major causes of dysphagia, making sensory stimulation in swallowing-related regions an important therapeutic strategy. The effectiveness of sensory stimuli (e.g., tactile, electrical, chemical) and their underlying molecular mechanisms to improve swallowing function are emerging research topics. Understanding the mechanism of swallowing is crucial to determine effective treatment strategies for dysphagia.

This Special Issue aims to highlight the current advancements in the neurophysiological basis of swallowing, emphasizing cellular and molecular mechanisms. It also aims to feature research papers dealing with the sensory stimulation strategy for dysphagia and its underlying mechanism. Both original and review papers are welcome.

Prof. Junichi Kitagawa
Dr. Mohammad Zakir Hossain
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • Neural control
  • Neurotransmitter system
  • Cellular and molecular mechanisms
  • Influence of orofacial sensory perception
  • Transduction mechanism of peripheral sensory inputs
  • Coordination of swallowing with other motor activity
  • Dysphagia mechanism under neurogenic disorders
  • Sensory stimulation therapy for dysphagia
  • Neurophysiological basis of sensory stimulation therapy
  • Molecular mechanism of sensory stimulation therapy

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Published Papers (5 papers)

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Research

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20 pages, 2198 KiB  
Article
Quipazine Elicits Swallowing in the Arterially Perfused Rat Preparation: A Role for Medullary Raphe Nuclei?
by Victor Bergé-Laval and Christian Gestreau
Int. J. Mol. Sci. 2020, 21(14), 5120; https://doi.org/10.3390/ijms21145120 - 20 Jul 2020
Cited by 8 | Viewed by 2801
Abstract
Pharmacological neuromodulation of swallowing may represent a promising therapeutic option to treat dysphagia. Previous studies suggested a serotonergic control of swallowing, but mechanisms remain poorly understood. Here, we investigated the effects of the serotonergic agonist quipazine on swallowing, using the arterially perfused working [...] Read more.
Pharmacological neuromodulation of swallowing may represent a promising therapeutic option to treat dysphagia. Previous studies suggested a serotonergic control of swallowing, but mechanisms remain poorly understood. Here, we investigated the effects of the serotonergic agonist quipazine on swallowing, using the arterially perfused working heart-brainstem (in situ) preparation in rats. Systemic injection of quipazine produced single swallows with motor patterns and swallow-breathing coordination similar to spontaneous swallows, and increased swallow rate with moderate changes in cardiorespiratory functions. Methysergide, a 5-HT2 receptor antagonist, blocked the excitatory effect of quipazine on swallowing, but had no effect on spontaneous swallow rate. Microinjections of quipazine in the nucleus of the solitary tract were without effect. In contrast, similar injections in caudal medullary raphe nuclei increased swallow rate without changes in cardiorespiratory parameters. Thus, quipazine may exert an excitatory effect on raphe neurons via stimulation of 5-HT2A receptors, leading to increased excitability of the swallowing network. In conclusion, we suggest that pharmacological stimulation of swallowing by quipazine in situ represents a valuable model for experimental studies. This work paves the way for future investigations on brainstem serotonergic modulation, and further identification of neural populations and mechanisms involved in swallowing and/or swallow-breathing interaction. Full article
(This article belongs to the Special Issue Molecular and Neural Mechanisms of Swallowing)
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11 pages, 2086 KiB  
Article
The Effects of Mutual Interaction of Orexin-A and Glucagon-Like Peptide-1 on Reflex Swallowing Induced by SLN Afferents in Rats
by Motoi Kobashi, Yuichi Shimatani, Masako Fujita, Yoshihiro Mitoh, Ryusuke Yoshida and Ryuji Matsuo
Int. J. Mol. Sci. 2020, 21(12), 4422; https://doi.org/10.3390/ijms21124422 - 22 Jun 2020
Cited by 2 | Viewed by 3268
Abstract
(1) Background: Our previous studies revealed that orexin-A, an appetite-increasing peptide, suppressed reflex swallowing via the commissural part of the nucleus tractus solitarius (cNTS), and that glucagon-like peptide-1 (GLP-1), an appetite-reducing peptide, also suppressed reflex swallowing via the medial nucleus of the NTS [...] Read more.
(1) Background: Our previous studies revealed that orexin-A, an appetite-increasing peptide, suppressed reflex swallowing via the commissural part of the nucleus tractus solitarius (cNTS), and that glucagon-like peptide-1 (GLP-1), an appetite-reducing peptide, also suppressed reflex swallowing via the medial nucleus of the NTS (mNTS). In this study, we examined the mutual interaction between orexin-A and GLP-1 in reflex swallowing. (2) Methods: Sprague–Dawley rats under urethane–chloralose anesthesia were used. Swallowing was induced by electrical stimulation of the superior laryngeal nerve (SLN) and was identified by the electromyographic (EMG) signals obtained from the mylohyoid muscle. (3) Results: The injection of GLP-1 (20 pmol) into the mNTS reduced the swallowing frequency and extended the latency of the first swallow. These suppressive effects of GLP-1 were not observed after the fourth ventricular administration of orexin-A. After the injection of an orexin-1 receptor antagonist (SB334867) into the cNTS, an ineffective dose of GLP-1 (6 pmol) into the mNTS suppressed reflex swallowing. Similarly, the suppressive effects of orexin-A (1 nmol) were not observed after the injection of GLP-1 (6 pmol) into the mNTS. After the administration of a GLP-1 receptor antagonist (exendin-4(5-39)), an ineffective dose of orexin-A (0.3 nmol) suppressed reflex swallowing. (4) Conclusions: The presence of reciprocal inhibitory connections between GLP-1 receptive neurons and orexin-A receptive neurons in the NTS was strongly suggested. Full article
(This article belongs to the Special Issue Molecular and Neural Mechanisms of Swallowing)
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Review

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17 pages, 346 KiB  
Review
Molecular and Neural Mechanism of Dysphagia Due to Cancer
by Ikuko Okuni, Yuta Otsubo and Satoru Ebihara
Int. J. Mol. Sci. 2021, 22(13), 7033; https://doi.org/10.3390/ijms22137033 - 29 Jun 2021
Cited by 14 | Viewed by 4602
Abstract
Cancer is one of the most common causes of death worldwide. Along with the advances in diagnostic technology achieved through industry–academia partnerships, the survival rate of cancer patients has improved dramatically through treatments that include surgery, radiation therapy, and pharmacotherapy. This has increased [...] Read more.
Cancer is one of the most common causes of death worldwide. Along with the advances in diagnostic technology achieved through industry–academia partnerships, the survival rate of cancer patients has improved dramatically through treatments that include surgery, radiation therapy, and pharmacotherapy. This has increased the population of cancer “survivors” and made cancer survivorship an important part of life for patients. The senses of taste and smell during swallowing and cachexia play important roles in dysphagia associated with nutritional disorders in cancer patients. Cancerous lesions in the brain can cause dysphagia. Taste and smell disorders that contribute to swallowing can worsen or develop because of pharmacotherapy or radiation therapy; metabolic or central nervous system damage due to cachexia, sarcopenia, or inflammation can also cause dysphagia. As the causes of eating disorders in cancer patients are complex and involve multiple factors, cancer patients require a multifaceted and long-term approach by the medical care team. Full article
(This article belongs to the Special Issue Molecular and Neural Mechanisms of Swallowing)
12 pages, 910 KiB  
Review
Diffuse Idiopathic Skeletal Hyperostosis of Cervical Spine with Dysphagia—Molecular and Clinical Aspects
by Mikołaj Dąbrowski and Łukasz Kubaszewski
Int. J. Mol. Sci. 2021, 22(8), 4255; https://doi.org/10.3390/ijms22084255 - 20 Apr 2021
Cited by 9 | Viewed by 3708
Abstract
Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterized by the calcification and ossification of the ligaments of the cervical spine; in some cases, it may result in dysphagia. The condition is more common in men over 50 years of age with metabolic [...] Read more.
Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterized by the calcification and ossification of the ligaments of the cervical spine; in some cases, it may result in dysphagia. The condition is more common in men over 50 years of age with metabolic disorders, and it is often asymptomatic and not a major issue for patients. The etiology of DISH is poorly understood, and known genetic factors indicate multiple signal pathways and multigene inheritance. In this review, we discuss the epidemiological, clinical, and etiological aspects of DISH with a special focus on dysphagia. Full article
(This article belongs to the Special Issue Molecular and Neural Mechanisms of Swallowing)
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45 pages, 1196 KiB  
Review
Targeting Chemosensory Ion Channels in Peripheral Swallowing-Related Regions for the Management of Oropharyngeal Dysphagia
by Mohammad Zakir Hossain, Hiroshi Ando, Shumpei Unno and Junichi Kitagawa
Int. J. Mol. Sci. 2020, 21(17), 6214; https://doi.org/10.3390/ijms21176214 - 27 Aug 2020
Cited by 17 | Viewed by 6755
Abstract
Oropharyngeal dysphagia, or difficulty in swallowing, is a major health problem that can lead to serious complications, such as pulmonary aspiration, malnutrition, dehydration, and pneumonia. The current clinical management of oropharyngeal dysphagia mainly focuses on compensatory strategies and swallowing exercises/maneuvers; however, studies have [...] Read more.
Oropharyngeal dysphagia, or difficulty in swallowing, is a major health problem that can lead to serious complications, such as pulmonary aspiration, malnutrition, dehydration, and pneumonia. The current clinical management of oropharyngeal dysphagia mainly focuses on compensatory strategies and swallowing exercises/maneuvers; however, studies have suggested their limited effectiveness for recovering swallowing physiology and for promoting neuroplasticity in swallowing-related neuronal networks. Several new and innovative strategies based on neurostimulation in peripheral and cortical swallowing-related regions have been investigated, and appear promising for the management of oropharyngeal dysphagia. The peripheral chemical neurostimulation strategy is one of the innovative strategies, and targets chemosensory ion channels expressed in peripheral swallowing-related regions. A considerable number of animal and human studies, including randomized clinical trials in patients with oropharyngeal dysphagia, have reported improvements in the efficacy, safety, and physiology of swallowing using this strategy. There is also evidence that neuroplasticity is promoted in swallowing-related neuronal networks with this strategy. The targeting of chemosensory ion channels in peripheral swallowing-related regions may therefore be a promising pharmacological treatment strategy for the management of oropharyngeal dysphagia. In this review, we focus on this strategy, including its possible neurophysiological and molecular mechanisms. Full article
(This article belongs to the Special Issue Molecular and Neural Mechanisms of Swallowing)
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