title: Plant-derived flavanol (-)epicatechin mitigates anxiety in association with elevated hippocampal monoamine and BDNF levels, but does not influence pattern separation in mice.
abstract: Flavanols found in natural products such as cocoa and green tea elicit structural and biochemical changes in the hippocampus, a brain area important for mood and cognition. Here, we evaluated the outcome of daily consumption of the flavanol (-)epicatechin (4 mg per day in water) by adult male C57BL/6 mice on measures of anxiety in the elevated plus maze (EPM) and open field (OF). Furthermore, pattern separation, the ability to distinguish between closely spaced identical stimuli, considered to be mediated by the hippocampal dentate gyrus (DG), was tested using the touchscreen. To investigate mechanisms through which (-)epicatechin may exert its effects, mice were injected with bromodeoxyuridine (50 mg kg(-1)) to evaluate adult hippocampal neurogenesis. In addition, monoaminergic and neurotrophin signaling pathway proteins were measured in tissue derived from subject cortices and hippocampi. Flavanol consumption reduced anxiety in the OF and EPM. Elevated hippocampal and cortical tyrosine hydroxylase, downregulated cortical monoamine oxidase-A levels, as well as increased hippocampal brain-derived neurotrophic factor (BDNF) and pro-BDNF support the flavanol's anxiolytic effects. In addition, elevated pAkt in hippocampus and cortex was observed. (-)Epicatechin ingestion did not facilitate touchscreen performance or DG neurogenesis, suggesting a non-neurogenic mechanism. The concurrent modulation of complementary neurotrophic and monoaminergic signaling pathways may contribute to beneficial mood-modulating effects of this flavanol.
authors.affiliation: Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Biomedical Research Center, Baltimore, MD, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: Stringer
authors.affiliation: Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Biomedical Research Center, Baltimore, MD, USA.
authors.forename: D
authors.initials: D
authors.lastname: Guerrieri
authors.affiliation: Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Biomedical Research Center, Baltimore, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Vivar
authors.affiliation: Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Biomedical Research Center, Baltimore, MD, USA.
authors.forename: H
authors.identifier: 000000025727434X
authors.initials: H
authors.lastname: van Praag
mesh_terms: D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects* / Q000378:metabolism; D002392:Catechin / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015536:Down-Regulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase; D055495:Neurogenesis / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012701:Serotonin; D002392:Catechin; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase; D004298:Dopamine; D009638:Norepinephrine