Neurodegeneration and functional impairments associated with glycogen synthase accumulation in a mouse model of Lafora disease.
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.
Affiliation: Institute for Research in Biomedicine (IRB Barcelona) Barcelona, Spain.Show MeSH
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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.
Affiliation: Institute for Research in Biomedicine (IRB Barcelona) Barcelona, Spain.