title: Neuropathology in respiratory-related motoneurons in young Pompe (Gaa(-/-)) mice.
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.
authors.affiliation: Department 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.
authors.forename: Sara M F
authors.initials: SM
authors.lastname: Turner
authors.affiliation: Department of Physical Therapy and McKnight Brain Institute, University of Florida, Gainesville, FL 32610, United States.
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Hoyt
authors.affiliation: Department of Pediatrics, Division of Pulmonary Medicine, University of Florida, Gainesville, FL 32610, United States.
authors.forename: Mai K
authors.initials: MK
authors.lastname: ElMallah
authors.affiliation: Department of Pediatrics, Child Health Research Institute, University of Florida, Gainesville, FL 32610, United States; Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610, United States; Center for Respiratory Research and Rehabilitation, University of Florida, Gainesville, FL 32610, United States.
authors.forename: Darin J
authors.initials: DJ
authors.lastname: Falk
authors.affiliation: Department of Pediatrics, Child Health Research Institute, University of Florida, Gainesville, FL 32610, United States; Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610, United States; Center for Respiratory Research and Rehabilitation, University of Florida, Gainesville, FL 32610, United States.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Byrne
authors.affiliation: Department 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. Electronic address: ddf@phhp.ufl.edu.
authors.forename: David D
authors.initials: DD
authors.lastname: Fuller
mesh_terms: D000818:Animals; D017209:Apoptosis; D002135:Calcium-Binding Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002574:Cervical Vertebrae; D015331:Cohort Studies; D004249:DNA Damage; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006009:Glycogen Storage Disease Type II / Q000378:metabolism / Q000473:pathology*; D008526:Medulla Oblongata / Q000378:metabolism / Q000473:pathology*; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology*; D015213:Neuroimmunomodulation; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D013904:Thoracic Vertebrae
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; C528900:glial fibrillary astrocytic protein, mouse; D006003:Glycogen; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: Glycogen; Hypoglossal; Intercostal; Lysosomal storage disease; Neurodegeneration; Phrenic