The effect of aging and chronic microglia activation on the morphology and numbers of the cerebellar Purkinje cells

Abstract

Reduced cerebellar volume and motor dysfunction have previously been observed in the GFAP-IL6 murine model of chronic neuroinflammation. This study aims to extend these findings by investigating the effect of microglial activation and ageing on the total number of Purkinje cells and the morphology of their dendritic arborization.Through comparison of transgenic GFAP-IL6 mice and their wild-type counterparts at the ages of 12 and 24-months, we were able to investigate the effects of ageing and chronic microglial activation on Purkinje cells. Unbiased stereology was used to estimate the number of microglia in Iba1+ stained tissue and Purkinje cells in calbindin stained tissue. Morphological analyses were made using 3D reconstructions of images acquired from the Golgi-stained cerebellar tissue.We found that the total number of microglia increased by approximately 5 times in the cerebellum of GFAP-IL6 mice compared to their WT littermates. The number of Purkinje cells decreased by as much as 50 % in aged wild type mice and 83 % in aged GFAP-IL6 mice. The remaining Purkinje cells in these cohorts were found to have significant reductions in their total dendritic length and number of branching points, indicating how the complexity of the Purkinje cell dendritic arbor reduces through age and inflammation.GFAP-IL6 mice, when compared to WT mice, had higher levels of microglial activation and more profound neurodegenerative changes in the cerebellum. The presence of constitutive IL6 production, driving chronic neuroinflammation, may account for these neurodegenerative changes in GFAP-IL6 mice.