Temporospatial Development of Neuropathologic Findings in a Canine Model of Mucopolysaccharidosis IIIB
| Autor: | Ariel S Nenninger, Bethann Valentine, N. Matthew Ellinwood, Jodi D. Smith, Tyler Harm, Shannon Jones Hostetter |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Pathology medicine.medical_specialty Mucopolysaccharidosis Article Pathogenesis Mucopolysaccharidosis III 03 medical and health sciences Dogs 0302 clinical medicine Dorsal root ganglion medicine Lysosomal storage disease Animals Dog Diseases skin and connective tissue diseases Neuroinflammation 030304 developmental biology Sanfilippo syndrome 0303 health sciences General Veterinary business.industry Brain Mucopolysaccharidoses medicine.disease Spinal cord Disease Models Animal medicine.anatomical_structure Gliosis Heparitin Sulfate medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Vet Pathol |
| ISSN: | 1544-2217 0300-9858 |
| Popis: | Mucopolysaccharidosis (MPS) IIIB is a neuropathic lysosomal storage disease characterized by the deficient activity of a lysosomal enzyme obligate for the degradation of the glycosaminoglycan (GAG) heparan sulfate (HS). The pathogenesis of neurodegeneration in MPS IIIB is incompletely understood. Large animal models are attractive for pathogenesis and therapeutic studies due to their larger size, outbred genetics, longer lifespan, and naturally occurring MPS IIIB disease. However, the temporospatial development of neuropathologic changes has not been reported for canine MPS IIIB. Here we describe lesions in 8 brain regions, cervical spinal cord, and dorsal root ganglion (DRG) in a canine model of MPS IIIB that includes dogs aged from 2 to 26 months of age. Pathological changes in the brain included early microscopic vacuolation of glial cells initially observed at 2 months, and vacuolation of neurons initially observed at 10 months. Inclusions within affected cells variably stained positively with PAS and LFB stains. Quantitative immunohistochemistry demonstrated increased glial expression of GFAP and Iba1 in dogs with MPS IIIB compared to age-matched controls at all time points, suggesting neuroinflammation occurs early in disease. Loss of Purkinje cells was initially observed at 10 months and was pronounced in 18- and 26-month-old dogs with MPS IIIB. Our results support the dog as a replicative model of MPS IIIB neurologic lesions and detail the pathologic and neuroinflammatory changes in the spinal cord and DRG of MPS IIIB-affected dogs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|