Histological Analysis of Phrenic Motor Neurons Pompe Disease

Pompe disease is a neuromuscular disorder resulting from mutations in the gene encoding acid α-glucosidase (GAA), an enzyme responsible for lysosomal glycogen degradation. Intravenous enzyme replacement therapy is the current standard of care but does not target the central nervous system (CNS). Respiratory failure is common in Pompe disease and data from animal models and Pompe patients indicate that the neural regulation of breathing can be impaired. The purpose of our study was to histologically evaluate phrenic motoneurons (PhrMNs) in a Gaa -/- rat model of Pompe disease. The retrograde marker cholera-toxin-β (CT-β) was delivered to the pleural space to label PhrMNs in 12-month old Gaa -/- and Sprague-Dawley rats. Cervical spinal cord sections were cut (25 µm) with a longitudinal orientation. Immunochemistry using the IV58B6 antibody was used to identify glycogen. Tissues were imaged using a 20x objective on a Keyence microscope. The general architecture of the phrenic motor nucleus was preserved in Pompe rats, with distinct clusters of PhrMNs arranged in a rostral-caudal fashion. However, PhrMN morphology was altered in Pompe rats, as evidenced by a swollen and vacuolized neural soma. Glycogen accumulation was prominent in Pompe PhrMNs but was never observed in S-D PhrMNs. Our results confirm that PhrMNs in the Gaa -/- rat model have extensive glycogen accumulation and show the prototypical histopathology expected for motor neurons in Pompe disease. The data support the notion that therapies to preserve breathing function in Pompe disease should target the CNS. R01HD052682 (DDF and BJB), 1K99NS133388-01A1 (SR) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.