Long-term Administration of Green Tea Catechins Prevents Age-Related Spatial Learning and Memory Decline in C57BL/6 J Mice by Regulating Hippocampal Cyclic Amp-Response Element Binding Protein Signaling Cascade

Neuroscience. 2009 Apr 10;159(4):1208-15. doi: 10.1016/j.neuroscience.2009.02.008. Epub 2009 Feb 11.

Abstract

Flavonoid-rich foods have been shown to be effective at reversing age-related deficits in learning and memory in both animals and humans. However, little investigation of the preventative effects of flavonoids on the naturally aged animals was reported. In our study, 14-month-old female C57BL/6 J mice were orally administered 0.025%, 0.05% and 0.1% green tea catechins (GTC, w/v) in drinking water for 6 months; we found that a supplementation with 0.05% or 0.1% GTC prevented age-related spatial learning and memory decline of mice in the Morris water maze. Better performance of GTC-treated mice was associated with increased levels of cAMP-response element binding protein (CREB) phosphorylation in the hippocampus. The expressions of brain-derived neurotrophic factor (BDNF) and Bcl-2, two target genes of CREB which can exhibit long-term regulatory roles in synaptic plasticity and synaptic structure, were also increased. We also found that long-term 0.05% or 0.1% GTC administration prevented age-related reductions of two representative post-synaptic density proteins PSD95 and Ca(2+)/calmodulin-dependent protein kinase II, suggesting that synaptic structural changes may be involved. These results demonstrated that long-term 0.05% or 0.1% green tea catechin administration may prevent age-related spatial learning and memory decline of female C57BL/6 J mice by regulating hippocampal CREB signaling cascade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects
  • Animals
  • Antioxidants / administration & dosage*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Catechin / administration & dosage*
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Disks Large Homolog 4 Protein
  • Female
  • Guanylate Kinases
  • Hippocampus / drug effects
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Learning / drug effects*
  • Maze Learning / drug effects
  • Membrane Proteins / metabolism
  • Memory / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Phosphorylation
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Random Allocation
  • Signal Transduction / drug effects
  • Space Perception / drug effects*

Substances

  • Antioxidants
  • Brain-Derived Neurotrophic Factor
  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Catechin
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Guanylate Kinases