Related Experiment Video
Updated: Mar 25, 2026
Repeated Measurement of Respiratory Muscle Activity and Ventilation in Mouse Models of Neuromuscular Disease
Published on: April 17, 2017
Neuropathology in respiratory-related motoneurons in young Pompe (Gaa(-/-)) mice
Sara M F Turner1, Aaron K Hoyt2, Mai K ElMallah3
1Department of Physical Therapy and McKnight Brain Institute, University of Florida, Gainesville, FL 32610, United States; Center for Respiratory Research and Rehabilitation, University of Florida, Gainesville, FL 32610, United States.
Abstract:
Respiratory and/or lingual dysfunction are among the first motor symptoms in Pompe disease, a disorder resulting from absence or dysfunction of the lysosomal enzyme acid α-glucosidase (GAA). Here, we histologically evaluated the medulla, cervical and thoracic spinal cords in 6 weeks old asymptomatic Pompe (Gaa(-/-)) mice to determine if neuropathology in respiratory motor regions has an early onset. Periodic acid-Schiff (PAS) staining indicated glycogen accumulation was exclusively occurring in Gaa(-/-) hypoglossal, mid-cervical and upper thoracic motoneurons. Markers of DNA damage (Tunel) and ongoing apoptosis (Cleaved Caspase 3) did not co-localize with PAS staining, but were prominent in a medullary region which included the nucleus tractus solitarius, and also in the thoracic spinal dorsal horn. We conclude that respiratory-related motoneurons are particularly susceptible to GAA deficiency and that neuronal glycogen accumulation and neurodegeneration may occur independently in early stage disease. The data support early therapeutic intervention in Pompe disease.
Insights
Early Pompe disease (GAA deficiency) causes glycogen buildup in respiratory motor neurons and neurodegeneration in other brain areas, supporting early treatment for this rare genetic disorder.
Area of Science:
- Neurology
- Genetics
- Biochemistry
Background:
- Pompe disease results from acid α-glucosidase (GAA) deficiency, leading to early motor symptoms like respiratory and lingual dysfunction.
- Neuropathology in respiratory motor regions may indicate early disease onset.
Purpose of the Study:
- To investigate early neuropathological changes in respiratory motor regions of asymptomatic Pompe disease mice.
- To determine if glycogen accumulation and neurodegeneration occur independently in early-stage Pompe disease.
Main Methods:
- Histological evaluation of medulla, cervical, and thoracic spinal cords in 6-week-old Gaa(-/-) mice.
- Periodic acid-Schiff (PAS) staining for glycogen detection.
- Immunohistochemistry for DNA damage (Tunel) and apoptosis (Cleaved Caspase 3) markers.
Main Results:
- Glycogen accumulation was observed exclusively in hypoglossal, mid-cervical, and upper thoracic motoneurons of Gaa(-/-) mice.
- DNA damage and apoptosis markers were prominent in the nucleus tractus solitarius and thoracic spinal dorsal horn, but not co-localized with glycogen.
- Respiratory-related motoneurons showed particular susceptibility to GAA deficiency.
Conclusions:
- Neuronal glycogen accumulation and neurodegeneration may occur independently in early Pompe disease.
- Early therapeutic intervention is supported by findings of neuropathology in respiratory motor regions.
- GAA deficiency impacts specific neuronal populations, contributing to early disease manifestations.
