Brain Stem Control of the Phases of Swallowing

Lang, Ivan M.

doi:10.1007/s00455-009-9211-6

Cited by 194 publications

(174 citation statements)

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“…It was supposed that aspiration pneumonia of these patients was the result of swallowing disturbances, which may be due to autonomic nervous system dysfunction (Kim et al 2000;Affoo et al 2013;Cereda et al 2014). This feature seems to be of special interest for the present study because dt-MP mice showed widespread neurodegenerative lesions in the brain stem, including nuclei important for the oral and pharyngeal phase of the swallowing process, namely the trigeminal nuclei and the pontine reticular formation (Lang 2009). A predisposition for a primary or secondary bacterial infection of the respiratory tract cannot be ruled out, although there were no obvious morphological changes in the investigated lymphoid organs like lymphoid depletion or disorders of the hematopoiesis concerning the bone marrow in the dt-MP mice.…”

Section: Discussionmentioning

confidence: 83%

Axonopathy in the Central Nervous System Is the Hallmark of Mice with a Novel Intragenic Null Mutation of Dystonin

et al. 2016

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Dystonia musculorum is a neurodegenerative disorder caused by a mutation in the dystonin gene. It has been described in mice and humans where it is called hereditary sensory autonomic neuropathy. Mutated mice show severe movement disorders and die at the age of 3-4 weeks. This study describes the discovery and molecular, clinical, as well as pathological characterization of a new spontaneously occurring mutation in the dystonin gene in C57BL/6N mice. The mutation represents a 40-kb intragenic deletion allele of the dystonin gene on chromosome 1 with exactly defined deletion borders. It was demonstrated by Western blot, mass spectrometry, and immunohistology that mice with a homozygous mutation were entirely devoid of the dystonin protein. Pathomorphological lesions were restricted to the brain stem and spinal cord and consisted of swollen, argyrophilic axons and dilated myelin sheaths in the white matter and, less frequently, total chromatolysis of neurons in the gray matter. Axonal damage was detected by amyloid precursor protein and nonphosphorylated neurofilament immunohistology. Axonopathy in the central nervous system (CNS) represents the hallmark of this disease. Mice with the dystonin mutation also showed suppurative inflammation in the respiratory tract, presumably due to brain stem lesion-associated food aspiration, whereas skeletal muscles showed no pathomorphological changes. This study describes a novel mutation in the dystonin gene in mice leading to axonopathy in the CNS. In further studies, this model may provide new insights into the pathogenesis of neurodegenerative diseases and may elucidate the complex interactions of dystonin with various other cellular proteins especially in the CNS. KEYWORDS axonopathy; dystonia musculorum; dystonin deficiency; genomic deletion; spontaneous mutation A spontaneously occurring mutant was described in the mouse, in which the gene dystonin was affected (Ledoux 2011). Dystonin (Dst) [human gene name, DST; former name, bullous pemphigoid antigen 1 (BPAG1)] is a large cytoskeletal linker protein and crucial for maintaining cellular structural integrity (Young and Kothary 2008). Recent research in this field concentrates on the role of dystonin in central nervous tissue and neurological diseases, but not, however, on its parallel expression in musculature and skin.Mice with a mutated dystonin gene develop a severe sensory neuropathy called dystonia musculorum (Duchen 1976). Characteristics are a progressive loss of coordination of the limbs (ataxia) and an early death (Kothary et al. 1988;Guo et al. 1995). There are only few reports about patients with mutations of the human dystonin gene (Giorda et al. 2004;Groves et al. 2010;Edvardson et al. 2012).Several dystonin isoforms are generated from one genomic locus of 400 kb. They are expressed in the central nervous system (CNS) (predominant neuronal isoform "a," 617 kDa and "n," 344 kDa), muscles (predominant muscle isoform "b," 834 kDa), and skin (predominant skin isoform "e," 302 kDa) ( Figure 1 Pool et al...

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Section: Discussionmentioning

confidence: 83%

Axonopathy in the Central Nervous System Is the Hallmark of Mice with a Novel Intragenic Null Mutation of Dystonin

et al. 2016

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“…3F, blue triangle), showed activity that was also negatively correlated with ratings of swallowing effort. The locations of these regions is rostral to nuclei in the medulla known to control the swallowing reflex (53,54). These medullary nuclei receive sensory input from the superior laryngeal nerve; stimulation of the nuclei (55), the nerve (55, 56), or regions innervated by the nerve, such as the epiglottis and larynx (57), initiate the swallowing reflex.…”

Section: Discussionmentioning

confidence: 99%

Overdrinking, swallowing inhibition, and regional brain responses prior to swallowing

Saker

Farrell

Egan

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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In humans, drinking replenishes fluid loss and satiates the sensation of thirst that accompanies dehydration. Typically, the volume of water drunk in response to thirst matches the deficit. Exactly how this accurate metering is achieved is unknown; recent evidence implicates swallowing inhibition as a potential factor. Using fMRI, this study investigated whether swallowing inhibition is present after more water has been drunk than is necessary to restore fluid balance within the body. This proposal was tested using ratings of swallowing effort and measuring regional brain responses as participants prepared to swallow small volumes of liquid while they were thirsty and after they had overdrunk. Effort ratings provided unequivocal support for swallowing inhibition, with a threefold increase in effort after overdrinking, whereas addition of 8% (wt/vol) sucrose to water had minimal effect on effort before or after overdrinking. Regional brain responses when participants prepared to swallow showed increases in the motor cortex, prefrontal cortices, posterior parietal cortex, striatum, and thalamus after overdrinking, relative to thirst. Ratings of swallowing effort were correlated with activity in the right prefrontal cortex and pontine regions in the brainstem; no brain regions showed correlated activity with pleasantness ratings. These findings are all consistent with the presence of swallowing inhibition after excess water has been drunk. We conclude that swallowing inhibition is an important mechanism in the overall regulation of fluid intake in humans.thirst | drinking | swallowing | inhibition | fMRI F luid depletion leads to drinking, an important evolutionary behavior that satisfies the physiological need to replenish lost fluid. The motivation to begin drinking is normally provided, in humans at least, by the presence of a subjective state of thirst. At some point after drinking has commenced, the sensation of thirst disappears and is replaced by the experience of satiation, along with the cessation of drinking. Studies performed in humans and animals indicate the regulatory mechanisms that have evolved to govern the cessation of drinking appear to be tightly calibrated, with the amount of fluid ingested commensurate with the degree of fluid depletion, even though some variation occurs between species regarding the time taken to conclude drinking (1-3).Several factors have been implicated in the regulation of fluid intake, with the majority relating to thirst and the initiation of drinking. These include signals produced by osmoreceptors in the lamina terminalis (4-6), which respond to cellular dehydration and the resulting increase in sodium concentration within the cerebral spinal fluid (2), and signals produced in response to extracellular dehydration, such as those associated with the renin-angiotensin system, which is activated as a result of changes in vascular pressure and volume (7,8). In comparison, the mechanisms responsible for terminating drinking are less well understood. Oropharyngeal metering ...

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“…These bulbar electrodiagnostic studies investigate paired cranial nerves VII, IX to X, and XII; the V to VII internuclear pathways; and the central pattern generator for swallowing involving the nucleus of the tractus solitarius and adjacent ventromedian reticular formation. 19 To that end, orofacial electrodiagnostic studies explore small-sized brainstem structures and cranial nerves that are not routinely studied by using MRI. 20,21 Among patients suffering from congenital facial malformations, electrodiagnostic studies have revealed the neurologic origin of dysphagia, even in the absence of neurologic signs or abnormalities in brain images.…”

Section: Discussionmentioning

confidence: 99%