Abstract：
:β-Amyloid (Aβ) elevation, tau hyperphosphorylation, and neuroinflammation are major hallmarks of Alzheimer's disease (AD). Glycogen synthase kinase-3β (GSK-3β) is a key protein kinase implicated in the pathogenesis of AD. Blockade of GSK-3β is an attractive therapeutic strategy for AD. Isoorientin, a 6-C-glycosylflavone, was previously shown to be a highly selective inhibitor of GSK-3β, while exerting neuroprotective effects in neuronal models of AD. In the present study, we evaluated the in vivo effects of isoorientin on GSK-3β, tau phosphorylation, Aβ deposition, neuroinflammatory response, long-term potentiation, and spatial memory in amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice using biochemical, electrophysiological, and behavioral tests. Chronic oral administration of isoorientin to APP/PS1 mice at 8 months of age attenuated multiple AD pathogenic hallmarks in the brains, including GSK-3β overactivation, tau hyperphosphorylation, Aβ deposition, and neuroinflammation. For neuroinflammation, isoorientin treatment reduced the number of activated microglia associated with Aβ-positive plaques, and in parallel reduced the levels of pro-inflammatory factors in the brains of APP/PS1 mice. Strikingly, isoorientin reversed deficits in synaptic long-term potentiation and spatial memory relevant to cognitive functions. Together, the findings suggest that isoorientin is a brain neuroprotector and may be a promising drug lead for treatment of AD and related neurodegenerative disorders.
journal_name
Behav Brain Resjournal_title
Behavioural brain researchauthors
Tan X,Liang Z,Li Y,Zhi Y,Yi L,Bai S,Forest KH,Nichols RA,Dong Y,Li QXdoi
10.1016/j.bbr.2020.112968subject
Has Abstractpub_date
2021-02-01 00:00:00pages
112968eissn
0166-4328issn
1872-7549pii
S0166-4328(20)30667-7journal_volume
398pub_type
杂志文章abstract：:This report summarizes 4 experiments which deal with the effects of surgical removal of the rat's telencephalic forebrain structures on performance of an inhibitory avoidance response, which was acquired either before or after the lesion was made. Two experiments provide evidence that inhibitory avoidance learning (us...
journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
pub_type： 杂志文章
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journal_title：Behavioural brain research
pub_type： 杂志文章
doi：10.1016/s0166-4328(97)02311-5
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journal_title：Behavioural brain research
pub_type： 杂志文章
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
pub_type： 杂志文章
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更新日期：2006-04-25 00:00:00
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journal_title：Behavioural brain research
pub_type： 杂志文章
doi：10.1016/s0166-4328(97)00199-x
更新日期：1998-11-01 00:00:00
