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Olfactory Deficits in Niemann-Pick Type C1 (NPC1) Disease
Authors:Marina Hovakimyan  Anja Meyer  Jan Lukas  Jiankai Luo  Volker Gudziol  Thomas Hummel  Arndt Rolfs  Andreas Wree  Martin Witt
Affiliation:1. Institute of Anatomy, Rostock University Medical Center, Rostock, Germany.; 2. Albrecht-Kossel Institute for Neuroregeneration, Rostock University Medical Center, Rostock, Germany.; 3. Department of Otorhinolaryngology, University of Dresden Medical School, Dresden, Germany.; Virginia Commonwealth University, United States of America,
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).

Methodology/Principal findings

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/Significance

Our data demonstrate a pronounced neurodegeneration and glia activation in the olfactory system of NPC1−/−, which is accompanied by sensory deficits.
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