title: Impaired neurite outgrowth in the retina of a murine model of Sandhoff disease.
abstract: OBJECTIVE
  To investigate the effects of lysosomal storage on the morphologic appearance and the neurite outgrowth capability of the retina in a mouse model of G(M2) gangliosidosis (Sandhoff disease).
  
  
  METHODS
  Histopathologic appearances of retinas in Sandhoff (SD) mice at 3 and 4 months of age were examined by light and electron microscopy. Retinas of SD mice and wild-type (WT) mice at 1, 2, and 4 months of age were cultured in collagen gel in the presence or absence of brain-derived neurotrophic factor (BDNF), and neurite outgrowth was examined.
  
  
  RESULTS
  Morphologic studies revealed accumulation of G(M2) ganglioside in the retinal ganglion cells of SD mice in a time-dependent manner. The number of neurites from the retinal explants after 7 and 10 days in culture were significantly lower in 2- and 4-month-old SD mice than in the age-matched WT mice. The application of BDNF significantly improved neurite outgrowth from the retina in both SD and WT mice at 2 months of age. At 4 months of age, BDNF was much less effective at stimulating neurite outgrowth in the retina of SD mice than in retina of WT mice.
  
  
  CONCLUSIONS
  These results indicate that lysosomal storage of G(M2) ganglioside impairs the capability of neurite outgrowth in retinal ganglion cells in culture and that BDNF is effective at diminishing this impairment during the early stage of the disease.
authors.affiliation: Department of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu-shi, Tokyo-183-8526, Japan. kazsango@tmin.ac.jp
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sango
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takano
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ajiki
authors.forename: Akiko
authors.initials: A
authors.lastname: Tokashiki
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Arai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kawano
authors.forename: Hidenori
authors.initials: H
authors.lastname: Horie
authors.forename: Shoji
authors.initials: S
authors.lastname: Yamanaka
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D004195:Disease Models, Animal; D005678:G(M2) Ganglioside / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000473:pathology* / Q000517:prevention & control; D016501:Neurites / Q000187:drug effects / Q000473:pathology*; D009924:Organ Culture Techniques; D012164:Retinal Diseases / Q000378:metabolism / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D012497:Sandhoff Disease / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D001619:beta-N-Acetylhexosaminidases / Q000172:deficiency / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005678:G(M2) Ganglioside; D001619:beta-N-Acetylhexosaminidases