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Fustin flavonoid attenuates β‐amyloid (1–42)‐induced learning impairment
Author(s) -
Jin ChunHui,
Shin EunJoo,
Park JaeBong,
Jang ChoonGon,
Li Zhengyi,
Kim Min Soo,
Koo Kyo Hwan,
Yoon HyoungJong,
Park SangJae,
Choi WonCheol,
Yamada Kiyofumi,
Nabeshima Toshitaka,
Kim HyoungChun
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22159
Subject(s) - creb , muscarinic acetylcholine receptor , chelerythrine , muscarinic acetylcholine receptor m1 , mapk/erk pathway , chemistry , endocrinology , medicine , pharmacology , choline acetyltransferase , protein kinase c , cholinergic , receptor , signal transduction , biology , biochemistry , transcription factor , gene
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 [ 3 H]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.