Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory

Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16568-73. doi: 10.1073/pnas.0607822103. Epub 2006 Oct 18.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Cyclic AMP / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Hippocampus / drug effects
  • Hippocampus / enzymology
  • Long-Term Potentiation / drug effects*
  • MAP Kinase Signaling System
  • Male
  • Memory / drug effects*
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Molecular Structure
  • Rats

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Flavonoids
  • Cyclic AMP
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • fisetin