Dissociation of frontotemporal dementia-related deficits and neuroinflammation in progranulin haploinsufficient mice.

摘要: Frontotemporal dementia (FTD) is a neurodegenerative disease with hallmark deficits in social and emotional function. Heterozygous loss-of-function mutations GRN, the progranulin gene, are common genetic cause of disorder, but mechanisms by which haploinsufficiency causes neuronal dysfunction FTD unclear. Homozygous knock-out (Grn(-/-)) mice have been studied as model this disorder show behavioral neuroinflammatory phenotype robust microglial activation. However, homozygous GRN causing complete deficiency were recently shown to different neurological ceroid lipofuscinosis, suggesting that total absence may effects distinct from those haploinsufficiency. Here, we heterozygous (Grn(+/-)) mice, We found Grn(+/-) developed age-dependent potentially relevant FTD. unlike Grn(-/-) occurred gliosis or increased expression tumor necrosis factor-α. Instead, abnormalities amygdala, an area selective vulnerability FTD, mice. Our findings indicate FTD-related resulting can develop detectable neuroinflammation, thereby dissociating activation functional important effect on neurons.