Astrocytes and neurons produce distinct types of polyglucosan bodies in Lafora disease. Issue 10 (26th August 2018)

• Record Type: Journal Article
• Authors: Augé, Elisabet; Pelegrí, Carme; Manich, Gemma; Cabezón, Itsaso; Guinovart, Joan J.; Duran, Jordi; Vilaplana, Jordi
• Is Part Of: Glia. Volume 66:Issue 10(2018)
• Page Start: 2094
• Page End: 2107
• Publication Date: 2018-08-26
• Subjects: corpora amylacea -- Lafora body -- malin -- natural antibody -- neo‐epitope; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.23463
• Languages: English
• ISSNs: 0894-1491

Abstract

Main Points: Absence of malin triggers the formation of polyglucosan bodies in neurons and enhances their development in astrocytes. These astrocytic polyglucosan bodies contain neo‐epitopes that are recognized by natural antibodies. Astrocytes are involved in the etiopathogenesis of Lafora disease. Abstract: Lafora disease (LD), the most devastating adolescence‐onset epilepsy, is caused by mutations in the EPM2A or EPM2B genes, which encode the proteins laforin and malin, respectively. Loss of function of one of these proteins, which are involved in the regulation of glycogen synthesis, induces the accumulation of polyglucosan bodies (PGBs)—known as Lafora bodies (LBs) and associated with neurons—in the brain. Ageing and some neurodegenerative conditions lead to the appearance of another type of PGB called corpora amylacea, which are associated with astrocytes and contain neo‐epitopes that can be recognized by natural antibodies. Here we studied the PGBs in the cerebral cortex and hippocampus of malin knockout mice, a mouse model of LD. These animals presented not only LBs associated with neurons but also a significant number of PGBs associated with astrocytes. These astrocytic PGBs were also increased in mice from senescence‐accelerated mouse‐prone 8 (SAMP8) strain and mice with overexpression of Protein Targeting to Glycogen (PTG OE ), indicating that they are not exclusive of LD. The astrocytic PGBs, but not neuronal LBs, contained neo‐epitopes that are recognized by natural antibodies. The astrocytic PGBs appeared predominantly in the hippocampus but were also present in some cortical brain regions, while neuronal LBs were found mainly in the brain cortex and the pyramidal layer of hippocampal regions CA2 and CA3. Our results indicate that astrocytes, contrary to current belief, are involved in the etiopathogenesis of LD.