title: Olfactory deficits in Niemann-Pick type C1 (NPC1) disease.
abstract: BACKGROUND
  Niemann-Pick type C disease (NPC) is a rare autosomal recessive lipid storage disease characterized by progressive neurodegeneration. As only a few studies have been conducted on the impact of NPC on sensory systems, we used a mutant mouse model (NPC1(-/-)) to examine the effects of this disorder to morphologically distinct regions of the olfactory system, namely the olfactory epithelium (OE) and olfactory bulb (OB).
  
  
  RESULTS
  For structural and functional analysis immunohistochemistry, electron microscopy, western blotting, and electrophysiology have been applied. For histochemistry and western blotting, we used antibodies against a series of neuronal and glia marker proteins, as well as macrophage markers. NPC1(-/-) animals present myelin-like lysosomal deposits in virtually all types of cells of the peripheral and central olfactory system. Especially supporting cells of the OE and central glia cells are affected, resulting in pronounced astrocytosis and microgliosis in the OB and other olfactory cortices. Up-regulation of Galectin-3, Cathepsin D and GFAP in the cortical layers of the OB underlines the critical role and location of the OB as a possible entrance gate for noxious substances. Unmyelinated olfactory afferents of the lamina propria seem less affected than ensheathing cells. Supporting the structural findings, electro-olfactometry of the olfactory mucosa suggests that NPC1(-/-) animals exhibit olfactory and trigeminal deficits.
  
  
  CONCLUSIONS
  Our data demonstrate a pronounced neurodegeneration and glia activation in the olfactory system of NPC1(-/-), which is accompanied by sensory deficits.
authors.affiliation: Institute of Anatomy, Rostock University Medical Center, Rostock, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Hovakimyan
authors.affiliation: Institute of Anatomy, Rostock University Medical Center, Rostock, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Meyer
authors.affiliation: Albrecht-Kossel Institute for Neuroregeneration, Rostock University Medical Center, Rostock, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Lukas
authors.affiliation: Albrecht-Kossel Institute for Neuroregeneration, Rostock University Medical Center, Rostock, Germany.
authors.forename: Jiankai
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Otorhinolaryngology, University of Dresden Medical School, Dresden, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Gudziol
authors.affiliation: Department of Otorhinolaryngology, University of Dresden Medical School, Dresden, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hummel
authors.affiliation: Albrecht-Kossel Institute for Neuroregeneration, Rostock University Medical Center, Rostock, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Rolfs
authors.affiliation: Institute of Anatomy, Rostock University Medical Center, Rostock, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wree
authors.affiliation: Institute of Anatomy, Rostock University Medical Center, Rostock, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Witt
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D037502:Galectin 3 / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009457:Neuroglia / Q000473:pathology / Q000502:physiology; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D009830:Olfactory Bulb / Q000473:pathology / Q000503:physiopathology; D009831:Olfactory Mucosa / Q000473:pathology / Q000503:physiopathology; D009833:Olfactory Pathways / Q000473:pathology / Q000503:physiopathology; D011506:Proteins / Q000235:genetics* / Q000502:physiology*; D012903:Smell / Q000235:genetics* / Q000502:physiology*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D015415:Biomarkers; D002402:Cathepsin D; D037502:Galectin 3; D047908:Intracellular Signaling Peptides and Proteins; D000077296:Niemann-Pick C1 Protein; D011506:Proteins; C577833:Abca1 protein, mouse; C485095:Lgals3 protein, mouse; C106831:Npc1 protein, mouse; C533923:Ctsd protein, mouse