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Neural Plasticity
Volume 2016, Article ID 3830424, 9 pages
Research Article

Miglustat Reverts the Impairment of Synaptic Plasticity in a Mouse Model of NPC Disease

1Department of Medical System, University of Rome Tor Vergata, 00133 Rome, Italy
2Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy
3IRCCS San Raffaele Pisana, 00163 Rome, Italy
4Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy
5National Centre for Rare Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy

Received 24 July 2015; Revised 15 October 2015; Accepted 1 November 2015

Academic Editor: Lucas Pozzo-Miller

Copyright © 2016 G. D’Arcangelo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Niemann-Pick type C disease is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol within the late endolysosomal compartment of cells and accumulation of gangliosides and other sphingolipids. Progressive neurological deterioration and insurgence of symptoms like ataxia, seizure, and cognitive decline until severe dementia are pathognomonic features of the disease. Here, we studied synaptic plasticity phenomena and evaluated ERKs activation in the hippocampus of BALB/c NPC1−/− mice, a well described animal model of the disease. Our results demonstrated an impairment of both induction and maintenance of long term synaptic potentiation in NPC1−/− mouse slices, associated with the lack of ERKs phosphorylation. We then investigated the effects of Miglustat, a recent approved drug for the treatment of NPCD. We found that in vivo Miglustat administration in NPC1−/− mice was able to rescue synaptic plasticity deficits, to restore ERKs activation and to counteract hyperexcitability. Overall, these data indicate that Miglustat may be effective for treating the neurological deficits associated with NPCD, such as seizures and dementia.