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

Chun Hui Jin, Eun Joo Shin, Jae Bong Park, Choon Gon Jang, Zhengyi Li, Min Soo Kim, Kyo Hwan Koo, Hyoung Jong Yoon, Sang Jae Park, Won Cheol Choi, Kiyofumi Yamada, Toshitaka Nabeshima, Hyoung Chun Kim

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40 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3658-3670
Number of pages13
JournalJournal of Neuroscience Research
Volume87
Issue number16
DOIs
Publication statusPublished - 01-12-2009

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

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    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., & Kim, H. C. (2009). Fustin flavonoid attenuates β-amyloid (1-42)-induced learning impairment. Journal of Neuroscience Research, 87(16), 3658-3670. https://doi.org/10.1002/jnr.22159