@article{824b252f971d4ea5b6f79b9988790207,
title = "Astrocytes and neurons produce distinct types of polyglucosan bodies in 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.",
keywords = "Lafora body, corpora amylacea, malin, natural antibody, neo-epitope",
author = "Elisabet Aug{\'e} and Carme Pelegr{\'i} and Gemma Manich and Itsaso Cabez{\'o}n and Guinovart, {Joan J.} and Jordi Duran and Jordi Vilaplana",
note = "Funding Information: IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain). This study was supported by grants BFU2013-47382-P, SAF-2014-54525-P, BFU2016-78398-P and BFU2017-84345-P from MINECO, by the Agencia Estatal de Investigaci{\'o}n (AEI), by European Regional Development Funds and a grant from the National Institute of Health (NIH-NINDS) P01NS097197. It was also funded by CIBER de Diabetes y Enfermedades Metab{\'o}licas and CIBER de Enfermedades Neurodegenerativas from the Instituto de Salud Carlos III. We thank the Generalitat de Catalunya for funding our research group (2014/SGR525). I. Cabez{\'o}n and E. Aug{\'e} received pre-doctoral “Ajuts de Personal Investigador en Formaci{\'o}” fellowships from the Universitat de Barcelona (APIF-UB). None of the supporting agencies had any role in performing the study or writing the manuscript. Funding Information: MINECO, Grant/Award Numbers: BFU2013-47382-P, SAF-2014-54525-P, BFU2016-78398-P, BFU2017-84345-P; Agencia Estatal de Investigaci{\'o}n (AEI); European Regional Development Funds; National Institute of Health (NIH-NINDS), Grant/Award Number: P01NS097197; CIBER de Diabetes y Enfermedades Metab{\'o}licas; CIBER de Enfermedades Neurodegenerativas from the Instituto de Salud Carlos III; Generalitat de Catalunya, Grant/Award Number: 2014/SGR525 Funding Information: information MINECO, Grant/Award Numbers: BFU2013-47382-P, SAF-2014-54525-P, BFU2016-78398-P, BFU2017-84345-P; Agencia Estatal de Investigaci?n (AEI); European Regional Development Funds; National Institute of Health (NIH-NINDS), Grant/Award Number: P01NS097197; CIBER de Diabetes y Enfermedades Metab?licas; CIBER de Enfermedades Neurodegenerativas from the Instituto de Salud Carlos III; Generalitat de Catalunya, Grant/Award Number: 2014/SGR525IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain). This study was supported by grants BFU2013-47382-P, SAF-2014-54525-P, BFU2016-78398-P and BFU2017-84345-P from MINECO, by the Agencia Estatal de Investigaci?n (AEI), by European Regional Development Funds and a grant from the National Institute of Health (NIH-NINDS) P01NS097197. It was also funded by CIBER de Diabetes y Enfermedades Metab?licas and CIBER de Enfermedades Neurodegenerativas from the Instituto de Salud Carlos III. We thank the Generalitat de Catalunya for funding our research group (2014/SGR525). I. Cabez?n and E. Aug? received pre-doctoral ?Ajuts de Personal Investigador en Formaci?? fellowships from the Universitat de Barcelona (APIF-UB). None of the supporting agencies had any role in performing the study or writing the manuscript. Publisher Copyright: {\textcopyright} 2018 Wiley Periodicals, Inc.",
year = "2018",
month = oct,
doi = "10.1002/glia.23463",
language = "English",
volume = "66",
pages = "2094--2107",
journal = "GLIA",
issn = "0894-1491",
publisher = "John Wiley & Sons Inc.",
number = "10",
}