کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5556772 | 1560548 | 2017 | 13 صفحه PDF | دانلود رایگان |
- Ciproxifan enhanced spatial memory and reduced reference as well as working memory error in APP transgenic mouse.
- Ciproxifan did not change the levels of Aβ1-40 and Aβ1-42 in APP transgenic mouse brain.
- Ciproxifan improved brain cholinergic activities in mouse brain.
- Ciproxifan reduced oxidative stress induced by amyloid plaques.
- Ciproxifan attenuated the amyloid-induced neuroinflammation.
AimThe present study is aimed to investigate the ability of ciproxifan, a histamine H3 receptor antagonist to inhibit β-amyloid (Aβ)-induced neurotoxicity in SK-N-SH cells and APP transgenic mouse model.Materials and methodsIn vitro studies was designed to evaluate the neuroprotective effects of ciproxifan in Aβ25-35 - induced SK-N-SH cells. For the in vivo study, ciproxifan (1 and 3 mg/kg, i.p.) was administrated to transgenic mice for 15 days and behaviour was assessed using the radial arm maze (RAM). Brain tissues were collected to measure Aβ levels (Aβ1-40 and Aβ1-42), acetylcholine (ACh), acetylcholinesterase (AChE), nitric oxide (NO), lipid peroxidation (LPO), antioxidant activities, cyclooxygenases (COX) and cytokines (IL-1α, IL-1β and IL-6), while plasma was collected to measure TGF-1β.ResultsThe in vitro studies demonstrated neuroprotective effect of ciproxifan by increasing cell viability and inhibiting reactive oxygen species (ROS) in Aβ25-35-induced SK-N-SH cells. Ciproxifan significantly improved the behavioural parameters in RAM. Ciproxifan however, did not alter the Aβ levels in APP transgenic mice. Ciproxifan increased ACh and showed anti-oxidant properties by reducing NO and LPO levels as well as enhancing antioxidant levels. The neuroinflammatory analysis showed that ciproxifan reduced both COX-1 and COX-2 activities, decreased the level of pro-inflammatory cytokines IL-1α, IL-1β and IL-6 and increased the level of anti-inflammatory cytokine TGF-1β.ConclusionThis present study provides scientific evidence of the use of ciproxifan via antioxidant and cholinergic pathways in the management of AD.
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Journal: Life Sciences - Volume 180, 1 July 2017, Pages 23-35