Astrocytes: new players in progressive myoclonus epilepsy of Lafora type
Open Access
- 1 April 2018
- journal article
- research article
- Published by Oxford University Press (OUP) in Human Molecular Genetics
- Vol. 27 (7), 1290-1300
- https://doi.org/10.1093/hmg/ddy044
Abstract
Lafora disease (LD) is a fatal form of progressive myoclonus epilepsy characterized by the accumulation of insoluble poorly branched glycogen-like inclusions named Lafora bodies (LBs) in the brain and peripheral tissues. In the brain, since its first discovery in 1911, it was assumed that these glycogen inclusions were only present in affected neurons. Mouse models of LD have been obtained recently, and we and others have been able to report the accumulation of glycogen inclusions in the brain of LD animals, what recapitulates the hallmark of the disease. In this work we present evidence indicating that, although in mouse models of LD glycogen inclusions co-localize with neurons, as originally established, most of them co-localize with astrocytic markers such as glial fibrillary acidic protein (GFAP) and glutamine synthase. In addition, we have observed that primary cultures of astrocytes from LD mouse models accumulate higher levels of glycogen than controls. These results suggest that astrocytes may play a crucial role in the pathophysiology of Lafora disease, as the accumulation of glycogen inclusions in these cells may affect their regular functionality leading them to a possible neuronal dysfunction.Funding Information
- Generalitat Valenciana (PrometeoII/2014/029)
- NIH
- NINDS (P01NS097197)
This publication has 46 references indexed in Scilit:
- Lafora bodies and neurological defects in malin-deficient mice correlate with impaired autophagyHuman Molecular Genetics, 2011
- Regional variation in mitochondrial DNA copy number in mouse brainBiochimica et Biophysica Acta (BBA) - Bioenergetics, 2011
- Astrocyte-Neuron Lactate Transport Is Required for Long-Term Memory FormationCell, 2011
- Ribonucleotide reductase is not limiting for mitochondrial DNA copy number in miceNucleic Acids Research, 2010
- Laforin, the most common protein mutated in Lafora disease, regulates autophagyHuman Molecular Genetics, 2010
- An enzymatic fluorimetric assay for glucose-6-phosphate: Application in an in vitro Warburg-like effectAnalytical Biochemistry, 2009
- Inhibition of glycogenolysis in astrocytes interrupts memory consolidation in young chickensGlia, 2006
- Timing of neuronal and glial ultrastructure disruption during brain slice preparation and recovery in vitroJournal of Comparative Neurology, 2003
- A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2)Human Molecular Genetics, 1999
- Functional Studies in Cultured AstrocytesMethods, 1998