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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Turner, SMF; Hoyt, AK; ElMallah, MK; Falk, DJ; Byrne, BJ; Fuller, DD

Published Date

  • June 15, 2016

Published In

Volume / Issue

  • 227 /

Start / End Page

  • 48 - 55

PubMed ID

  • 26921786

Pubmed Central ID

  • PMC4880056

Electronic International Standard Serial Number (EISSN)

  • 1878-1519

Digital Object Identifier (DOI)

  • 10.1016/j.resp.2016.02.007


  • eng

Conference Location

  • Netherlands