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- W2766337519 abstract "Epidemiological studies suggest that moderate consumption of alcoholic beverages is beneficial for preventing dementia, but there are few reports about the effective constituents except for resveratrol in red wines. In the present study, we evaluated the effects of iso-α-acids, hop-derived bitter compounds in beer on the development of Alzheimer's disease. To evaluate the effects of iso-α-acids on microglia, primary CD11b-positive microglia were treated with iso-α-acids, and then with lipopolysaccharide for anti-inflammatory activity or with Aβ-fluorescein for phagocytic activity. Next, 3-month-old 5xFAD male mice, a model for Alzheimer's disease, were fed with a diet containing 0 or 0.05% (w/w) iso-α-acids for 2.5 months. At 5.5-month-old, episodic memory function was evaluated by novel object recognition test. The amounts of Aβ1–42, cytokines, neurotrophic factors, and synaptophysin in the brain were quantified by ELISA. The expressions of surface markers of microglia were analyzed with a flow cytometer. Iso-α-acids treatments enhanced microglial phagocytosis of Aβ and suppressed the production of TNF-α by the stimulation of lipopolysaccharide. The treatment also changed microglial phenotype to CD206-positive anti-inflammatory one and enhanced the expression of CD36, a scavenger receptor. In the 5xFAD mice, the intake of iso-α-acid significantly suppressed soluble and insoluble Aβ1–42 accumulations in the cerebral cortex. Both phagocytic activity and expression of CD36 in microglia were significantly lower in 5xFAD mice than in age-matched control mice, whereas oral administration of iso-α-acids alleviated the dysfunctions in 5xFAD mice. The concentrations of IL-1β, TNF-α and MIP-1α in the cerebral cortex were significantly higher in the 5xFAD mice than in age-matched control mice. Oral administration of iso-α-acids also alleviated the increase in cytokine and chemokine levels in 5xFAD mice. The amount of BDNF and synaptophysin were also significantly increased in the 5xFAD mice fed with iso-α-acid compared with the mice without iso-α-acid. In the object recognition tests, the time ratio exploring around the novel object and the discrimination index were significantly improved in 5xFAD mice given iso-α-acids as compared with control 5xFAD mice. The present study first reported that iso-α-acids, bitter ingredients of beer, might have preventive effects on the development of Alzheimer's disease via the regulation of microglia." @default.
- W2766337519 created "2017-11-10" @default.
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- W2766337519 date "2017-07-01" @default.
- W2766337519 modified "2023-10-17" @default.
- W2766337519 title "[P2-039]: ISO-α-ACIDS, BITTER COMPONENTS OF BEER, PREVENT CEREBRAL INFLAMMATION AND COGNITIVE DECLINE IN A MOUSE MODEL OF ALZHEIMER's DISEASE" @default.
- W2766337519 doi "https://doi.org/10.1016/j.jalz.2017.06.687" @default.
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