An astrocytic cellular model of Lafora disease to study polyglucosan accumulation and inflammation.

Abstract

Lafora disease (LD) is a devastating form of progressive myoclonus epilepsy characterized by the accumulation of insoluble forms of glycogen [polyglucosan bodies (PGBs)] in the brain and peripheral tissues. It has been proposed that the accumulation of PGBs is pathogenic. Several mouse models of LD have been generated to study the relationship between PGBs and the pathophysiology of LD. However, the use of LD mice is difficult and time consuming; thus, more amenable cellular systems would be desirable. We recently described a cellular model based on the culture of primary postnatal astrocytes from LD mice that are able to accumulate small PGBs. In this study, we extended this astrocytic model by maturing the astrocytes for longer times. These more mature astrocyte cultures accumulated larger and granular PGBs, which have similar properties to the ones present in the hippocampus of Nhlrc1-/- (Epm2b-/-) mice. Importantly, this model expresses inflammatory mediators related to LD pathophysiology. This astrocytic model could be used to better understand the formation of the PGBs and also to define how the accumulation of PGBs activates the expression of inflammatory mediators.