Research Article

Fustin flavonoid attenuates β-amyloid (1–42)-induced learning impairment

  1. Chun-Hui Jin1,†,
  2. Eun-Joo Shin1,†,
  3. Jae-Bong Park2,
  4. Choon-Gon Jang3,
  5. Zhengyi Li1,
  6. Min Soo Kim1,
  7. Kyo Hwan Koo1,
  8. Hyoung-Jong Yoon1,
  9. Sang-Jae Park4,
  10. Won-Cheol Choi5,
  11. Kiyofumi Yamada6,
  12. Toshitaka Nabeshima7,
  13. Hyoung-Chun Kim1,*

Article first published online: 16 JUN 2009

DOI: 10.1002/jnr.22159

Issue

Journal of Neuroscience Research

Journal of Neuroscience Research

Volume 87, Issue 16, pages 3658–3670, December 2009

Additional Information

How to Cite

Jin, C.-H., Shin, E.-J., Park, J.-B., Jang, C.-G., Li, Z., Kim, M. S., Koo, K. H., Yoon, H.-J., Park, S.-J., Choi, W.-C., Yamada, K., Nabeshima, T. and Kim, H.-C. (2009), Fustin flavonoid attenuates β-amyloid (1–42)-induced learning impairment. Journal of Neuroscience Research, 87: 3658–3670. doi: 10.1002/jnr.22159

Author Information

  1. 1

    Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, South Korea

  2. 2

    Department of Biochemistry, College of Medicine, Hallym University, Chunchon, South Korea

  3. 3

    Department of Pharmacology, College of Pharmacy, Sungkyunkwan University, Suwon, South Korea

  4. 4

    AZI Company Lt. 319 Chunchon Bio-Industry Foundation, Chunchon, South Korea

  5. 5

    MU Integrative Cancer Center, East-West Medical Center, Kyunghee University, Seoul, South Korea

  6. 6

    Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan

  7. 7

    Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya, Japan

  1. †

    The first two authors contributed equally to this work.

*Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea

Publication History

  1. Issue published online: 15 OCT 2009
  2. Article first published online: 16 JUN 2009
  3. Manuscript Accepted: 21 MAY 2009
  4. Manuscript Revised: 19 MAR 2009
  5. Manuscript Received: 18 FEB 2009

Funded by

  • Brain Research Center from 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea. Grant Number: 2009K001253
  • Academic Frontier Project for Private Universities (2007–2011) from the Ministry of Education, Culture, Sports, Science and Technology, Japan
  • BK 21 Program

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Keywords:

  • fustin;
  • β-amyloid;
  • hippocampus;
  • muscarinic M1 receptor;
  • learning and memory

Abstract

Natural flavonoids ameliorate amyloid-β peptide (Aβ)-induced neurotoxicity. We examined whether the fustin flavonoid affects Aβ-induced learning impairment in mice. Repeated treatment with fustin significantly attenuated Aβ (1–42)-induced conditioned fear and passive avoidance behaviors. This effect was comparable to that of EGb761, a standard extract of ginkgo. Fustin treatment significantly prevented decreases in acetylcholine (ACh) levels, choline acetyltransferase (ChAT) activity, and ChAT gene expression induced by Aβ (1–42). Fustin also consistently suppressed increases in acetyl cholinesterase (AChE) activity and AChE gene expression induced by Aβ (1–42). In addition, fustin significantly attenuated Aβ (1–42)-induced selective decreases in muscarinic M1 receptor gene expression and muscarinic M1 receptor binding activity (as determined by [3H]pirenzepine binding) by modulating extracellular signal-regulated kinase 1/2 (ERK 1/2) and cAMP response-element binding protein (CREB) phosphorylation and brain-derived neurotrophic factor (BDNF) expression. These effects of fustin were reversed by treatment with dicyclomine, a muscarinic M1 receptor antagonist, and SL327, a selective ERK inhibitor, but not by chelerythrine, a pan-protein kinase C (PKC) inhibitor. Taken together, our results suggest that fustin attenuates Aβ (1–42)-impaired learning, and that the ERK/CREB/BDNF pathway is important for the M1 receptor-mediated cognition-enhancing effects of fustin. © 2009 Wiley-Liss, Inc.

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