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Behavioral deficits, early gliosis, dysmyelination and synaptic dysfunction in a mouse model of mucolipidosis IV.
- Source :
-
Acta neuropathologica communications [Acta Neuropathol Commun] 2014 Sep 09; Vol. 2, pp. 133. Date of Electronic Publication: 2014 Sep 09. - Publication Year :
- 2014
-
Abstract
- Mucolipidosis IV (MLIV) is caused by mutations in the gene MCOLN1. Patients with MLIV have severe neurologic deficits and very little is known about the brain pathology in this lysosomal disease. Using an accurate mouse model of mucolipidosis IV, we observed early behavioral deficits which were accompanied by activation of microglia and astrocytes. The glial activation that persisted during the course of disease was not accompanied by neuronal loss even at the late stage. In vivo [Ca(2+)]-imaging revealed no changes in resting [Ca(2+)] levels in Mcoln1(-/-) cortical neurons, implying their physiological health. Despite the absence of neuron loss, we observed alterations in synaptic plasticity, as indicated by elevated paired-pulse facilitation and enhanced long-term potentiation. Myelination deficits and severely dysmorphic corpus callosum were present early and resembled white matter pathology in mucolipidosis IV patients. These results indicate the early involvement of glia, and challenge the traditional view of mucolipidosis IV as an overtly neurodegenerative condition.
- Subjects :
- Animals
Astrocytes pathology
Disease Models, Animal
Exploratory Behavior physiology
Gliosis
Male
Mice
Mice, Knockout
Microglia pathology
Motor Activity physiology
Myelin Sheath pathology
Neuronal Plasticity
Neurons physiology
Transient Receptor Potential Channels genetics
Brain pathology
Brain physiopathology
Mucolipidoses pathology
Mucolipidoses physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 2051-5960
- Volume :
- 2
- Database :
- MEDLINE
- Journal :
- Acta neuropathologica communications
- Publication Type :
- Academic Journal
- Accession number :
- 25200117
- Full Text :
- https://doi.org/10.1186/s40478-014-0133-7