Behavioral deficits and progressive neuropathology in progranulin-deficient mice: a mouse model of frontotemporal dementia

[摘要] Progranulin haploinsufficiency causes frontotemporal dementia with tau-negative, ubiquitin-positive neuronal inclusion pathology. In this study, we showed that progranulin-deficient mice displayed increased depression- and disinhibition-like behavior, as well as deficits in social recognition from a relatively young age. These mice did not have any deficit in locomotion or exploration. Eighteen-month-old progranulin-deficient mice demonstrated impaired spatial learning and memory in the Morris water maze. In addition to behavioral deficits, progranulin-deficient mice showed a progressive development of neuropathology from 12 mo of age, including enhanced activation of microglia and astro-cytes and ubiquitination and cytoplasmic accumulation of phosphorylated TDP-43. Thus, progranulin deficiency induced FTD-like behavioral and neuropathological deficits. These mice may serve as an important tool for deciphering underlying mechanisms in frontotemporal dementia.-Yin, F., Dumont, M., Banerjee, R., Ma, Y., Li, H., Lin, M. T., Beal, M. F., Nathan, C., Thomas, B., Ding, A. Behavioral deficits and progressive neuropathology in progranulin-deficient mice: a mouse model of frontotemporal dementia. FASEB J. 24, 4639-4647 (2010). www.fasebj.org

[发布日期] 2010-12-01

[关键词] LOBAR DEGENERATION;EPITHELIN PRECURSOR;HOST-DEFENSE;INFLAMMATION;INCLUSIONS;ACROGRANIN;MUTATIONS;DISEASE;REPAIR;ROLES