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• W2181245904 endingPage "14.2015" @default.
• W2181245904 startingPage "ENEURO.0061" @default.
• W2181245904 abstract "Loss-of-function mutations in progranulin (GRN) are one of the most common genetic causes of frontotemporal dementia (FTD), a progressive, fatal neurodegenerative disorder with no available disease-modifying treatments. Through haploinsufficiency, these mutations reduce levels of progranulin, a protein that has neurotrophic and anti-inflammatory effects. Increasing progranulin expression from the intact allele is therefore a potential approach for treating individuals with GRN mutations. Based on the well-known effects of physical exercise on other neurotrophic factors, we hypothesized that exercise might increase brain progranulin levels. We tested this hypothesis in progranulin heterozygous (Grn+/-) mice, which model progranulin haploinsufficiency. We housed wild-type and progranulin-insufficient mice in standard cages or cages with exercise wheels for 4 or 7.5 weeks, and then measured brain and plasma progranulin levels. Although exercise modestly increased progranulin in very young (2-month-old) wild-type mice, this effect was limited to the hippocampus. Exercise did not increase brain progranulin mRNA or protein in multiple regions, nor did it increase plasma progranulin, in 4- to 8-month-old wild-type or Grn+/- mice, across multiple experiments and under conditions that increased hippocampal BDNF and neurogenesis. Grn-/- mice were included in the study to test for progranulin-independent benefits of exercise on gliosis. Exercise attenuated cortical microgliosis in 8-month-old Grn-/- mice, consistent with a progranulin-independent, anti-inflammatory effect of exercise. These results suggest that exercise may have some modest, nonspecific benefits for FTD patients with progranulin mutations, but do not support exercise as a strategy to raise progranulin levels." @default.
• W2181245904 created "2016-06-24" @default.
• W2181245904 creator A5055043813 @default.
• W2181245904 creator A5062583689 @default.
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• W2181245904 date "2015-05-01" @default.
• W2181245904 modified "2023-10-14" @default.
• W2181245904 title "Effects of Exercise on Progranulin Levels and Gliosis in Progranulin-Insufficient Mice" @default.
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• W2181245904 doi "https://doi.org/10.1523/eneuro.0061-14.2015" @default.
• W2181245904 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4562684" @default.
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