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• W1904080998 abstract "Background and purpose There is emerging evidence suggesting that abnormal transport of amyloid-β (Aβ) across the blood-brain barrier (BBB) is involved in diabetes-associated cognitive decline. We investigated whether PPARγ agonists restore Aβ transport across the BBB and hippocampal plasticity in db/db mice. Experimental approach Efflux and influx of Aβ across the BBB were determined by stereotaxic intra-cerebral or i.a. infusion of [(125) I]-Aβ1-40 respectively. Receptor for advanced glycation end products (RAGE) and low-density lipoprotein receptor-related protein 1 (LRP1), which are involved in Aβ influx and efflux, PPARγ and NF-κB p65 at the BBB, as well as hippocampal Aβ, caspase-3, Bax and Bcl-2 were assayed by Western blot, immunohistochemistry and RT-PCR. In vivo, hippocampal LTP was recorded, and Morris water maze and Y-maze tasks were performed. Key results Treatment with PPARγ agonists, rosiglitazone (0.8 mg·kg(-1) ) and pioglitazone (9.0 mg·kg(-1) ), for 6 weeks significantly increased Aβ efflux and decreased Aβ influx across the BBB in db/db mice. Concomitantly, they decreased hippocampal Aβ1-40 and Aβ1-42 , suppressed neuronal apoptosis, as indicated by decreased caspase-3 activity and increased ratio of Bcl-2/Bax, and increased hippocampal plasticity, characterized by an enhanced in vivo LTP and better performance in behavioural tests. Furthermore, the PPARγ agonists induced the expression of LRP1 gene by activation of PPARγ and suppressed RAGE gene expression by inactivation of NF-κB signalling at the BBB of db/db mice. Conclusions and implications PPARγ agonists modify abnormal Aβ transport across the BBB and this is accompanied by amelioration of β-amyloidosis and an improvement in hippocampal plasticity in diabetic mice." @default.
• W1904080998 created "2016-06-24" @default.
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• W1904080998 date "2015-12-19" @default.
• W1904080998 modified "2023-10-10" @default.
• W1904080998 title "PPARγ agonists regulate bidirectional transport of amyloid-β across the blood-brain barrier and hippocampus plasticity in<i>db</i>/<i>db</i>mice" @default.
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• W1904080998 doi "https://doi.org/10.1111/bph.13378" @default.
• W1904080998 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5341223" @default.
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