ABSTRACT
The vagal and glossopharyngeal sensory ganglia and their peripheral tissues were examined in wild type and dystonia musculorum mice to assess the effect of dystonin loss of function on chemoreceptive neurons. In the mutant mouse, the number of vagal and glossopharyngeal sensory neurons was severely decreased (70% reduction) when compared with wild type littermates. The mutation also reduced the size of the circumvallate papilla (45% reduction) and the number of taste buds (89% reduction). In addition, immunohistochemical analysis demonstrated that the dystonin mutation reduced the number of PGP 9.5-, calcitonin gene-related peptide-, P2X3 receptor- and tyrosine hydroxylase-containing neurons. Their peripheral endings also decreased in the taste bud and epithelium of circumvallate papillae. These data together suggest that the survival of vagal and glossopharyngeal sensory neurons is dependent upon dystonin.
Subject(s)
Carrier Proteins/physiology , Cytoskeletal Proteins/physiology , Ganglia, Sensory/abnormalities , Glossopharyngeal Nerve/abnormalities , Nerve Tissue Proteins/physiology , Neurons, Afferent/metabolism , Vagus Nerve/abnormalities , Animals , Animals, Newborn , Calcitonin Gene-Related Peptide/metabolism , Carrier Proteins/genetics , Cell Differentiation/genetics , Cell Survival/genetics , Chemoreceptor Cells/abnormalities , Chemoreceptor Cells/metabolism , Chemoreceptor Cells/pathology , Cytoskeletal Proteins/genetics , Down-Regulation/genetics , Dystonin , Ganglia, Sensory/metabolism , Ganglia, Sensory/pathology , Glossopharyngeal Nerve/metabolism , Glossopharyngeal Nerve/pathology , Mice , Mice, Transgenic , Nerve Tissue Proteins/genetics , Neurons, Afferent/pathology , Nodose Ganglion/abnormalities , Nodose Ganglion/metabolism , Nodose Ganglion/pathology , Receptors, Purinergic P2/metabolism , Receptors, Purinergic P2X3 , Sensory Receptor Cells/abnormalities , Sensory Receptor Cells/metabolism , Sensory Receptor Cells/pathology , Taste/genetics , Taste Buds/abnormalities , Taste Buds/pathology , Tyrosine 3-Monooxygenase/metabolism , Ubiquitin Thiolesterase/metabolism , Vagus Nerve/metabolism , Vagus Nerve/pathologyABSTRACT
Abnormalities of the chemical control of breathing may go unrecognized and lead to life-threatening events, especially during sleep. Tests to assess chemical control in vivo have not yet been standardized, and their results may be difficult to interpret. Non-invasive monitoring of gas exchange and polysomnography are essential to assess the severity of hypoventilation and the extent to which it is dependent on the state of alertness. One has to be aware that some patients may have increased vulnerability to stress, and that mild infections may trigger acute hypoventilation. To date, no pharmacological approaches have proved effective in the long-term. Therefore, the management of infants and children with abnormal chemical control of breathing includes ventilatory support during sleep and diaphragmatic pacing during wakefulness, if necessary. Further research is needed to improve our understanding of the mechanisms controlling chemosensitivity and of the developmental plasticity of chemosensitivity during infancy and childhood. Genetic influences, as well as environmental factors in utero or during early infancy, may contribute to abnormal chemical control of breathing during infancy and childhood.