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Quercetin protects against the Aβ‐induced amnesic injury through inhibiting RAGE‐mediated pathway and preserving the neurovascular unit
Author(s) -
Liu Rui,
Zhou Dan,
Bai Xiaoyu,
Du Guanhua
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb507
Subject(s) - quercetin , neurovascular bundle , pharmacology , morris water navigation task , medicine , neuroscience , cholinergic , hippocampus , chemistry , psychology , pathology , antioxidant , biochemistry
Quercetin is one of the most common flavonoids existing widely in many edible plants. It has demonstrated protective effects against Aβ‐induced toxicity on both neurons and endothelial cells. However, whether or not quercetin has an effect on the neurovascular coupling is unclear. In the present study, we aim to investigate the anti‐amnesic effects of quercetin and to explore the underlying mechanisms. The aggregated Aβ25–35 was injected into the right lateral ventricle in mice. Quercetin was administrated orally for 8 days after injection. Learning and memory behaviors were evaluated by measuring spontaneous alternation in Morris Water Maze test and the step‐through positive avoidance test. The regional cerebral blood flow was monitored before the Aβ25–35 injection and on seven consecutive days after injection. Mice were sacrificed and cerebral cortices were isolated on the last day. The effects of quercetin on the neurovascular unit (NVU) integrity, microvascular function and cholinergic neuronal changes, and the modification of signaling pathways were tested. Our results demonstrate that quercetin treatment for Aβ25–35‐induced amnesic mice improved the learning and memory capabilities and conferred robust neurovascular coupling protection. In these effects, quercetin improved the spatial learning and memory effectively across the acquisition training period and the memory capability trials in behavioral tests. Furthermore, quercetin maintained the integrity of NVU major components, reduced the level of neurovascular oxidation, modulated the rCBF value of cerebral microvessels, improved the function of cholinergic system, and regulated the neurovascular RAGE signaling and ERK/CREB/BDNF pathways. In conclusion, in Aβ25–35‐induced amnesic mice, optimal doses of quercetin administration were beneficial. Quercetin protected the NVU through reduction of oxidative damage, inactivation of RAGE‐mediated pathway and preservation of cholinergic neurons, offering an alternative medication for Alzheimer's disease. Support or Funding Information This work was supported by National Natural Science Foundation of China (No. 81102830, 81073120), Beijing New‐star Plan of Science and Technology (xx2013065), and Beijing Organization Department Excellent Talents Project (2013D0090087).