Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation

ABSTRACT: Microglia repair injury and maintain homeostasis in the brain, but whether aberrant microglial activation can contribute to neurodegeneration remains unclear. Here, we use transcriptome profiling to demonstrate that deficiency in frontotemporal dementia (FTD) gene progranulin (Grn) leads to an age-dependent, progressive up-regulation of lysosomal and innate immunity genes, increased complement production, and synaptic pruning activity in microglia. During aging, Grn-/- mice show profound accumulation of microglia and preferential elimination of inhibitory synapses in the ventral thalamus, which contribute to hyperexcitability in the thalamocortical circuits and obsessive-compulsive disorder (OCD)-like grooming behaviors. Remarkably, blocking complement activation by deleting C1qa gene sign

ORGANISM(S): Mus musculus

SUBMITTER: Giovanni Coppola 

PROVIDER: E-GEOD-75083 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress