Astrocytes and neurons produce distinct types of polyglucosan bodies in Lafora disease
| Autor: | Jordi Duran, Gemma Manich, Itsaso Cabezón, Jordi Vilaplana, Elisabet Augé, Joan J. Guinovart, Carme Pelegrí |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cytoplasm Hippocampus Astròcits Mice Transgenic Hippocampal formation Biology Article Lafora disease 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine medicine Malalties hereditàries Animals Glycogen synthase Glucans Cerebral Cortex Inclusion Bodies Neurons medicine.disease Citoplasma Cell biology Disease Models Animal 030104 developmental biology medicine.anatomical_structure Lafora Disease Neurology Cerebral cortex Astrocytes Knockout mouse biology.protein Corpora amylacea Laforin 030217 neurology & neurosurgery Genetic diseases |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|