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Neurodegeneration and functional impairments associated with glycogen synthase accumulation in a mouse model of Lafora disease.

Valles-Ortega J, Duran J, Garcia-Rocha M, Bosch C, Saez I, Pujadas L, Serafin A, Cañas X, Soriano E, Delgado-García JM, Gruart A, Guinovart JJ - EMBO Mol Med (2011)

Bottom Line: They also had LBs in the soma and some processes of PV(+) interneurons.This phenomenon was accompanied by the progressive loss of these neuronal cells and, importantly, neurophysiological alterations potentially related to impairment of hippocampal function.Our results emphasize the relevance of the laforin-malin complex in the control of glycogen metabolism and highlight altered glycogen accumulation as a key contributor to neurodegeneration in LD.

View Article: PubMed Central - PubMed

Affiliation: Institute for Research in Biomedicine (IRB Barcelona) Barcelona, Spain.

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Histological localization of LBs in malin KO mouse brainsLBs are MGS-positive.Periodic acid-Schiff staining (PAS) and immunostaining with an antibody against muscle glycogen synthase (MGS) are shown for the hippocampus and cerebellum of 4- and 11-month-old malin KO and 11-month-old WT littermate controls. Scale bar = 100 µm, 4X = 4-fold magnification.Representative orthogonal confocal sections of LBs showing co-localization (yellow) of polyglucosan (red) and MGS (green) in malin KO brains. Scale bar = 10µm.
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fig01: Histological localization of LBs in malin KO mouse brainsLBs are MGS-positive.Periodic acid-Schiff staining (PAS) and immunostaining with an antibody against muscle glycogen synthase (MGS) are shown for the hippocampus and cerebellum of 4- and 11-month-old malin KO and 11-month-old WT littermate controls. Scale bar = 100 µm, 4X = 4-fold magnification.Representative orthogonal confocal sections of LBs showing co-localization (yellow) of polyglucosan (red) and MGS (green) in malin KO brains. Scale bar = 10µm.

Mentions: We bred malin KO mice up to about 1 year of age. These animals accumulated LBs, the hallmark of LD. LBs were present in several areas of the brain, being most abundant in the hippocampus and cerebellum (Fig 1A). No comparable structures in corresponding regions of control littermate animals were found. LB accumulation was not exclusive to the brain, as they were also detected in some fibres of skeletal muscle and heart (Supporting Information Fig 1). The inclusions increased in number and size with age, as can be seen by comparing 4- and 11-month-old mice (Figs 1A and 7B). Moreover, in the older mice, LBs were detected in regions of the brain that were unaffected at 4 months (Fig 1A). This result is consistent with the accumulative nature of LD.


Neurodegeneration and functional impairments associated with glycogen synthase accumulation in a mouse model of Lafora disease.

Valles-Ortega J, Duran J, Garcia-Rocha M, Bosch C, Saez I, Pujadas L, Serafin A, Cañas X, Soriano E, Delgado-García JM, Gruart A, Guinovart JJ - EMBO Mol Med (2011)

Histological localization of LBs in malin KO mouse brainsLBs are MGS-positive.Periodic acid-Schiff staining (PAS) and immunostaining with an antibody against muscle glycogen synthase (MGS) are shown for the hippocampus and cerebellum of 4- and 11-month-old malin KO and 11-month-old WT littermate controls. Scale bar = 100 µm, 4X = 4-fold magnification.Representative orthogonal confocal sections of LBs showing co-localization (yellow) of polyglucosan (red) and MGS (green) in malin KO brains. Scale bar = 10µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3377110&req=5

fig01: Histological localization of LBs in malin KO mouse brainsLBs are MGS-positive.Periodic acid-Schiff staining (PAS) and immunostaining with an antibody against muscle glycogen synthase (MGS) are shown for the hippocampus and cerebellum of 4- and 11-month-old malin KO and 11-month-old WT littermate controls. Scale bar = 100 µm, 4X = 4-fold magnification.Representative orthogonal confocal sections of LBs showing co-localization (yellow) of polyglucosan (red) and MGS (green) in malin KO brains. Scale bar = 10µm.
Mentions: We bred malin KO mice up to about 1 year of age. These animals accumulated LBs, the hallmark of LD. LBs were present in several areas of the brain, being most abundant in the hippocampus and cerebellum (Fig 1A). No comparable structures in corresponding regions of control littermate animals were found. LB accumulation was not exclusive to the brain, as they were also detected in some fibres of skeletal muscle and heart (Supporting Information Fig 1). The inclusions increased in number and size with age, as can be seen by comparing 4- and 11-month-old mice (Figs 1A and 7B). Moreover, in the older mice, LBs were detected in regions of the brain that were unaffected at 4 months (Fig 1A). This result is consistent with the accumulative nature of LD.

Bottom Line: They also had LBs in the soma and some processes of PV(+) interneurons.This phenomenon was accompanied by the progressive loss of these neuronal cells and, importantly, neurophysiological alterations potentially related to impairment of hippocampal function.Our results emphasize the relevance of the laforin-malin complex in the control of glycogen metabolism and highlight altered glycogen accumulation as a key contributor to neurodegeneration in LD.

View Article: PubMed Central - PubMed

Affiliation: Institute for Research in Biomedicine (IRB Barcelona) Barcelona, Spain.

Show MeSH
Related in: MedlinePlus