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Miglustat Reverts the Impairment of Synaptic Plasticity in a Mouse Model of NPC Disease.
- Source :
-
Neural plasticity [Neural Plast] 2016; Vol. 2016, pp. 3830424. Date of Electronic Publication: 2016 Jan 14. - Publication Year :
- 2016
-
Abstract
- 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.
- Subjects :
- 1-Deoxynojirimycin pharmacology
Animals
Disease Models, Animal
Extracellular Signal-Regulated MAP Kinases metabolism
Hippocampus metabolism
Hippocampus physiopathology
Mice
Niemann-Pick Disease, Type C metabolism
Phosphorylation drug effects
Synapses metabolism
1-Deoxynojirimycin analogs & derivatives
Enzyme Inhibitors pharmacology
Hippocampus drug effects
Neuronal Plasticity drug effects
Niemann-Pick Disease, Type C physiopathology
Synapses drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1687-5443
- Volume :
- 2016
- Database :
- MEDLINE
- Journal :
- Neural plasticity
- Publication Type :
- Academic Journal
- Accession number :
- 26885401
- Full Text :
- https://doi.org/10.1155/2016/3830424