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    Puerarin attenuates locomotor and cognitive deficits as well as hippocampal neuronal injury through the PI3K/Akt1/GSK-3 beta signaling pathway in an in vivo model of cerebral ischemia

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    22290-315627-4-PB.pdf
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    Author
    Tao, Jinhao
    Cui, Yuehua
    Duan, Yu
    Zhang, Nan
    Wang, Congmin
    Zhang, Fayong
    Affiliation
    Univ Arizona, Dept Basic Med Sci
    Issue Date
    2017-11-07
    Keywords
    cerebral ischemia/reperfusion
    puerarin
    hippocampus
    Akt
    GSK-3 beta
    
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    Publisher
    IMPACT JOURNALS LLC
    Citation
    Puerarin attenuates locomotor and cognitive deficits as well as hippocampal neuronal injury through the PI3K/Akt1/GSK-3 beta signaling pathway in an in vivo model of cerebral ischemia 2017, 8 (63) Oncotarget
    Journal
    Oncotarget
    Rights
    © Tao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0).
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    Ischemic stroke causes irreversible damage to the brain. The hippocampus is a vulnerable region and plays an important role in cognition and locomotor activity. Puerarin is a phytoestrogen that has beneficial effects in treating neurological disorders. How puerarin protects against hippocampal injury and its molecular mechanisms remain to be elucidated. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats. The rats were pretreated with puerarin alone or together with LY294002 (an PI3K inhibitor) before ischemia/ reperfusion (I/R). The open-and closed-field tasks and Morris water maze (MWM) test were used to assess the effects of puerarin on anxiety-like behavioral and cognitive impairment following I/R. Hematoxylin-eosin staining(HE) was used to examine the survival of hippocampal CA1 pyramidal neurons, and immunoblotting was performed to examine the expression of the related proteins. By using the rat model for transient I/R, we demonstrated that puerarin pretreatment significantly increased the travelling distance and number of crossings in the open-and closedfield tests, reduced latency and increased the proportion of distance and time in zone IV in the MWM. The number of live cells in the hippocampus is sharply increased by puerarin pretreatment. We further observed that the levels of phosphorylated Akt1, GSK-3 beta and MCL-1were elevated and those of cleaved-caspase-3 were reduced in the puerarin-treatment group. Notably, the PI3K inhibitor LY294002 counteracted all of the effects of puerarin. Our findings suggest that puerarin protects the hippocampus from I/R damage by activating the PI3K/Akt1/GSK-3 beta/MCL-1 signaling pathway.
    ISSN
    1949-2553
    PubMed ID
    29290948
    DOI
    10.18632/oncotarget.22290
    Version
    Final published version
    Sponsors
    National Natural Science Foundation of China [81271296]
    Additional Links
    http://www.oncotarget.com/fulltext/22290
    ae974a485f413a2113503eed53cd6c53
    10.18632/oncotarget.22290
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    UA Faculty Publications

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