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
Related in: MedlinePlus
Mentions: Available in vivo recording techniques allow the study of hippocampal synapses in awake mice (Gruart et al, 2006; Madronal et al, 2009). Both WT and transgenic KO mice presented increases in the slope of fEPSP evoked at the CA1 area following the presentation of paired pulses (40 ms of inter-pulse interval) of increasing intensity at the ipsilateral Schaffer collaterals (Fig 8A). Nevertheless, KO mice presented significantly larger fEPSP amplitudes than WT animals at high stimulus intensities (>0.2 mA), suggesting an enhanced synaptic excitability.
Affiliation: Institute for Research in Biomedicine (IRB Barcelona) Barcelona, Spain.