Neuropathology in respiratory-related motoneurons in young Pompe (Gaa(-/-)) mice

Respir Physiol Neurobiol. 2016 Jun 15;227:48-55. doi: 10.1016/j.resp.2016.02.007. Epub 2016 Feb 26.


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.

Keywords: Glycogen; Hypoglossal; Intercostal; Lysosomal storage disease; Neurodegeneration; Phrenic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Calcium-Binding Proteins / metabolism
  • Caspase 3 / metabolism
  • Cervical Vertebrae
  • Cohort Studies
  • DNA Damage
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein / metabolism
  • Glycogen / metabolism
  • Glycogen Storage Disease Type II / metabolism
  • Glycogen Storage Disease Type II / pathology*
  • Medulla Oblongata / metabolism
  • Medulla Oblongata / pathology*
  • Mice, 129 Strain
  • Mice, Knockout
  • Microfilament Proteins / metabolism
  • Motor Neurons / metabolism
  • Motor Neurons / pathology*
  • Neuroimmunomodulation
  • Spinal Cord / metabolism
  • Spinal Cord / pathology*
  • Thoracic Vertebrae


  • Aif1 protein, mouse
  • Calcium-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Microfilament Proteins
  • glial fibrillary astrocytic protein, mouse
  • Glycogen
  • Casp3 protein, mouse
  • Caspase 3