title: Neuropathological changes in the peripheral nervous system and spinal cord in a transgenic mouse model of Niemann-Pick disease type A.
abstract: OBJECTIVE
  Type A Niemann-Pick is a severe neurological disease, caused by a mutation of the gene of acid sphingomyelinase (ASM) and reduced enzyme activity. Some studies reported neuropathological changes occurring in the central nervous system of ASM deficient transgenic (ASMKO) mice, while a detailed study on the peripheral nervous system (PNS) at different ages is currently lacking. The aim of our study was to examine the pathological changes occurring in the PNS and in the spinal cord in an AMSKO model of Niemann-Pick disease (NPD) Type A.
  
  
  METHODS
  Dorsal root ganglia (DRG), peripheral nerves and spinal cord specimens were obtained from ASMKO mice and age-matched wild type animals (age range = 1-7 months). They were observed at the light and electron microscope. Behavioral testing was performed to assess motor coordination and reactivity. Fluoro-Jade B was used as a high affinity fluorescent marker for degenerating neurons.
  
  
  RESULTS
  Typical NPD cytoplasmic inclusions were observed in DRG neurons and satellite cells, in peripheral nerve Schwann cells, in spinal cord neurons and in endothelial cells. All these inclusions were present from the age of 1 month and increased with aging. By Fluoro-Jade B staining we demonstrated the occurrence of neuronal degeneration starting from 5 months of age.
  
  
  CONCLUSIONS
  Despite the fact that a definite diagnosis of NPD Type A depends on enzymatic assays and/or molecular analysis, morphological investigation remains an important diagnostic procedure. Well-defined and complete neuropathological information about the ASMKO mouse model, inclusive of PNS examination, may be crucial in the pre-clinical evaluation of new therapies.
authors: Department of Neurosciences and Biomedical Technologies, University of Milan Bicocca, Monza, Italy. paola.marmiroli@unimib.it
authors: P
authors: P
authors: Marmiroli
authors: V
authors: V
authors: Rodriguez-Menendez
authors: L
authors: L
authors: Rigamonti
authors: E
authors: E
authors: Tonoli
authors: R
authors: R
authors: Rigolio
authors: G
authors: G
authors: Cavaletti
authors: G
authors: G
authors: Tredici
authors: A
authors: A
authors: Vercelli
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005452:Fluoresceins; D051379:Mice; D008822:Mice, Transgenic; D052536:Niemann-Pick Disease, Type A / Q000473:pathology*; D009930:Organic Chemicals; D017933:Peripheral Nervous System / Q000473:pathology*; D013108:Sphingomyelin Phosphodiesterase / Q000172:deficiency / Q000235:genetics; D013116:Spinal Cord / Q000473:pathology*
chemical_list: D005452:Fluoresceins; D009930:Organic Chemicals; C435731:fluoro jade; D013108:Sphingomyelin Phosphodiesterase