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• W2004561499 abstract "Previous studies suggested that amyloid β (Aβ)-induced disruption of astrocytic Ca2+ signalling and oxidative stress play a major role in the progression towards neuronal and glial death in Alzheimer's disease. We have recently demonstrated that Ca2+-permeable TRPV4 channels are highly expressed in rat hippocampal astrocytes and are involved in oxidative stress-induced cell damage. The aim of this study was to test the hypothesis that TRPV4 channels also contribute to hippocampal damage evoked by Aβ. Synthetic Aβ40 evoked cell death in hippocampal slice cultures in a concentration (0–20 μM) and time (12–48 h) dependent manner, after cultures were preconditioned with sublethal concentration of buthionine sulfoximine (1.5 μM) which enhanced endogenous ROS production. As demonstrated by propidium iodide fluorescence, damage was observed in the granule cell layer of the dentate gyrus and to a smaller degree in pyramidal neurons of the CA1–CA3 region, as well as in glia cells mainly at the edge of the slice. Immunocytochemistry revealed an altered pattern of TRPV4 and GFAP protein expression, and reactive astrogliosis surrounding pyramidal CA1–CA3 neurons. Neuronal and astrocytic damage was attenuated by the antioxidant Trolox, TRPV4 channel blockers Gd3+ and ruthenium red (RR), and a specific inhibitor of the redox and Ca2+-sensitive phospholipase A2 enzyme (MAFP). In disassociated co-cultures of hippocampal neurons and astrocytes without BSO preconditioning, Aβ40 evoked pronounced neuronal damage, enhanced the expression of TRPV4 and GFAP proteins (indicative of reactive astrogliosis), and increased intracellular free Ca2+ concentration in astrocytes. The latter effect was attenuated by RR and in Ca2+-free media. These data show that Aβ40 can activate astrocytic TRPV4 channels in the hippocampus, leading to neuronal and astrocytic damage in a Ca2+ and oxidative stress-dependent manner." @default.
• W2004561499 created "2016-06-24" @default.
• W2004561499 creator A5009328818 @default.
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• W2004561499 date "2014-03-01" @default.
• W2004561499 modified "2023-10-18" @default.
• W2004561499 title "Involvement of TRPV4 channels in Aβ40-induced hippocampal cell death and astrocytic Ca2+ signalling" @default.
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• W2004561499 doi "https://doi.org/10.1016/j.neuro.2014.01.001" @default.
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