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It has been suggested that histamine H3 receptors (H3Rs) modulate tau phosphorylation. In the current study, the effects of the H3R agonist, ciproxifan, on tau phosphorylation were evaluated in 3×Tg-AD mice. Mice received ciproxifan (20mg/kg, i.p.) daily for 4 weeks. The impact of ciproxifan on Aβ accumulation, synaptic integrity and neuronal loss was also determined. Ciproxifan administration led to decreased H3R immunoreactivity and elevated histamine levels in the cerebral cortex and hippocampus. Tau hyperphosphorylation and acetylation were reduced following ciproxifan treatment. We also demonstrated that ciproxifan administration significantly improved the cognitive impairment and reduced Aβ levels in 3×Tg-AD mice. The protective effects of ciproxifan against Aβ-induced neuronal loss and synaptic integrity loss were also confirmed. These findings provide evidence that ciproxifan is a promising compound that can alleviate tau hyperphosphorylation and thus may provide a potential new approach for prevention and treatment of AD.Buy Facebook likes
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