Berberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer's disease transgenic mouse model

S S Kumar DURAIRAJAN, Liangfeng LIU, Jia Hong Lu, Lei Lei Chen, Qiuju Yuan, Sookja K. Chung, Ling Huang, Xing Shu Li, Jian Dong Huang, Min LI*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

161 Citations (Scopus)

Abstract

The accumulation of β-amyloid (Aβ) peptide derived from abnormal processing of amyloid precursor protein (APP) is a common pathological hallmark of Alzheimer's disease (AD) brains. In this study, we evaluated the therapeutic effect of berberine (BBR) extracted from Coptis chinensis Franch, a Chinese medicinal herb, on the neuropathology and cognitive impairment in TgCRND8 mice, a well established transgenic mouse model of AD. Two-month-old TgCRND8 mice received a low (25 mg/kg per day) or a high dose of BBR (100 mg/kg per day) by oral gavage until 6 months old. BBR treatment significantly ameliorated learning deficits, long-term spatial memory retention, as well as plaque load compared with vehicle control treatment. In addition, enzyme-linked immunosorbent assay (ELISA) measurement showed that there was a profound reduction in levels of detergent-soluble and -insoluble β-amyloid in brain homogenates of BBR-treated mice. Glycogen synthase kinase (GSK)3, a major kinase involved in APP and tau phosphorylation, was significantly inhibited by BBR treatment. We also found that BBR significantly decreased the levels of C-terminal fragments of APP and the hyperphosphorylation of APP and tau via the Akt/glycogen synthase kinase 3 signaling pathway in N2a mouse neuroblastoma cells stably expressing human Swedish mutant APP695 (N2a-SwedAPP). Our results suggest that BBR provides neuroprotective effects in TgCRND8 mice through regulating APP processing and that further investigation of the BBR for therapeutic use in treating AD is warranted.

Original languageEnglish
Pages (from-to)2903-2919
Number of pages17
JournalNeurobiology of Aging
Volume33
Issue number12
DOIs
Publication statusPublished - Dec 2012

Scopus Subject Areas

  • Neuroscience(all)
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

User-Defined Keywords

  • β-amyloid
  • Alzheimer's disease
  • Amyloid precursor protein
  • Berberine
  • Glycogen synthase kinase
  • Tau phosphorylation
  • TgCRND8 mice

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