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Journal article
Hypoglossal neuropathology and respiratory activity in Pompe mice
Frontiers in physiology, v 2, pp 31-31
01 Jan 2011
PMID: 21747768
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Pompe disease is a lysosomal storage disorder associated with systemic deficiency of acid a-glucosidase (GAA). Respiratory-related problems in Pompe disease include hypoventilation and upper airway dysfunction. Although these problems have generally been attributed to muscular pathology, recent work has highlighted the potential role of central nervous system (CNS) neuropathology in Pompe motor deficiencies. We used a murine model of Pompe disease to test the hypothesis that systemic GAA deficiency is associated with hypoglossal (XII) motoneuron pathology and altered XII motor output during breathing. Brainstem tissue was harvested from adult Gaa mice and the periodic acid Schiff method was used to examine neuronal glycogen accumulation. Semi-thin (2 Rm) plastic sections showed widespread medullary neuropathology with extensive cytoplasmic glycogen accumulation in XII motoneuron soma. We next recorded efferent XII bursting in anesthetized and ventilated Gaa and B6/129 mice both before and after bilateral vagotomy. The coefficient of variation of respiratory cycle duration was greater in Gaa(-/-) compared to B6/129 mice (p < 0.01). Vagotomy caused a robust increase in XII inspiratory burst amplitude in B6/129 mice (239 +/- 44% baseline; p < 0.01) but had little impact on burst amplitude in Gaa mice (130 +/- 23% baseline; p > 0.05). We conclude that CNS GAA deficiency results in substantial glycogen accumulation in XII motoneuron cell bodies and altered XII motor output. Therapeutic strategies targeting the CNS may be required to fully correct respiratory-related deficits in Pompe disease.
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Details
- Title
- Hypoglossal neuropathology and respiratory activity in Pompe mice
- Creators
- Kun-Ze Lee - McKnight Brain InstituteKai Qiu - McKnight Brain InstituteMilapjit S. Sandhu - McKnight Brain InstituteMai K. Elmallah - University of FloridaDarin J. Falk - University of FloridaMichael A. Lane - McKnight Brain InstitutePaul J. Reier - McKnight Brain InstituteBarry J. Byrne - University of FloridaDavid D. Fuller - McKnight Brain Institute
- Publication Details
- Frontiers in physiology, v 2, pp 31-31
- Publisher
- Frontiers Media Sa
- Number of pages
- 10
- Grant note
- P01 DK58327-03 / NIDDK; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) 1R01HD052682-01A1; HL59412; 5F32HL095282-02 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000209172600031
- Scopus ID
- 2-s2.0-84866181597
- Other Identifier
- 991019299100904721
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- Web of Science research areas
- Physiology