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Berberine Alleviates Amyloid-beta Pathogenesis Via Activating LKB1/AMPK Signaling in the Brain of APP/PS1 Transgenic Mice

[ Vol. 19 , Issue. 5 ]

Author(s):

Zhi-You Cai*, Chuan-Ling Wang, Tao-Tao Lu and Wen-Ming Yang   Pages 342 - 348 ( 7 )

Abstract:


Background: Liver kinase B1 (LKB1)/5’-adenosine monophosphate-activated protein kinase (AMPK) signaling, a metabolic checkpoint, plays a neuro-protective role in the pathogenesis of Alzheimer’s disease (AD). Amyloid-β (Aβ) acts as a classical biomarker of AD. The aim of the present study was to explore whether berberine (BBR) activates LKB1/AMPK signaling and ameliorates Aβ pathology.

Methods: The Aβ levels were detected using enzyme-linked immunosorbent assay and immunohistochemistry. The following biomarkers were measured by Western blotting: phosphorylated (p-) LKB1 (Ser334 and Thr189), p-AMPK (AMPKα and AMPKβ1), synaptophysin, post-synaptic density protein 95 and p-cAMP-response element binding protein (p-CREB). The glial fibrillary acidic protein (GFAP) was determined using Western blotting and immunohistochemistry.

Results: BBR inhibited Aβ expression in the brain of APP/PS1 mice. There was a strong up-regulation of both p-LKB1 (Ser334 and Thr189) and p-AMPK (AMPKα and AMPKβ1) in the brains of APP/PS1 transgenic mice after BBR-treatment (P<0.01). BBR promoted the expression of synaptophysin, post-synaptic density protein 95 and p-CREB(Ser133) in the AD brain, compared with the model mice.

Conclusion: BBR alleviates Aβ pathogenesis and rescues synapse damage via activating LKB1/AMPK signaling in the brain of APP/PS1 transgenic mice.

Keywords:

Berberine, amyloid-β, liver kinase B1, 5'-adenosine monophosphate-activated protein kinase, pathogenesis, LKB1/AMPK signaling.

Affiliation:

Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, 400013, Chongqing, Department of Pathology, Chongqing Medical University, Chongqing, 400010, Chongqing, Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031 Anhui Province, Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031 Anhui Province



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