Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory.
Small molecules that activate signaling pathways used by neurotrophic factors could be useful for treating CNS disorders. Here we show that the flavonoid fisetin activates ERK and induces cAMP response element-binding protein (CREB) phosphorylation in rat hippocampal slices, facilitates long-term potentiation in rat hippocampal slices, and enhances object recognition in mice. Together, these data demonstrate that the natural product fisetin can facilitate long-term memory, and therefore it may be useful for treating patients with memory disorders.
Maher
Pamela
P
The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. pmaher@salk.edu
Akaishi
Tatsuhiro
T
Abe
Kazuho
K
D000818:Animals; D001522:Behavior, Animal; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D044948:Flavonols; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D017774:Long-Term Potentiation / Q000187:drug effects*; D020935:MAP Kinase Signaling System; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D015394:Molecular Structure; D051381:Rats
D017362:Cyclic AMP Response Element-Binding Protein; D005419:Flavonoids; D044948:Flavonols; D000242:Cyclic AMP; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C017875:fisetin