Progranulin Deficiency Decreases Gross Neural Connectivity But Enhances Transmission at Individual Synapses

摘要: Frontotemporal dementia (FTD) has been linked to mutations in the progranulin gene (GRN) that lead (PGRN) haploinsufficiency. Thus far, our understanding of effects PGRN depletion brain derived from investigation gross pathology, and more detailed analyses cellular function have lacking. We report knocking down levels rat primary hippocampal cultures reduces neural connectivity by decreasing neuronal arborization length as well synapse density. Despite this, number synaptic vesicles per frequency mEPSCs are increased knockdown cells, suggesting an increase probability release at remaining synapses. Interestingly, we demonstrate is also postmortem sections FTD patients with haploinsufficiency, relative controls. Our observations show severely alters vitro vesicle phenotype observed culture consistent hippocampus patients.