PMID- 25562843 OWN - NLM STAT- MEDLINE DCOM- 20150909 LR - 20181113 IS - 2158-3188 (Electronic) IS - 2158-3188 (Linking) VI - 5 IP - 1 DP - 2015 Jan 6 TI - Plant-derived flavanol (-)epicatechin mitigates anxiety in association with elevated hippocampal monoamine and BDNF levels, but does not influence pattern separation in mice. PG - e493 LID - 10.1038/tp.2014.135 [doi] AB - 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. FAU - Stringer, T P AU - Stringer TP AD - Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Biomedical Research Center, Baltimore, MD, USA. FAU - Guerrieri, D AU - Guerrieri D AD - Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Biomedical Research Center, Baltimore, MD, USA. FAU - Vivar, C AU - Vivar C AD - Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Biomedical Research Center, Baltimore, MD, USA. FAU - van Praag, H AU - van Praag H AUID- ORCID: 000000025727434X AD - Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Biomedical Research Center, Baltimore, MD, USA. LA - eng GR - Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural DEP - 20150106 PL - United States TA - Transl Psychiatry JT - Translational psychiatry JID - 101562664 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 333DO1RDJY (Serotonin) RN - 8R1V1STN48 (Catechin) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - EC 1.4.3.4 (Monoamine Oxidase) RN - VTD58H1Z2X (Dopamine) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Animals MH - *Anxiety MH - Behavior, Animal/*drug effects MH - Brain-Derived Neurotrophic Factor/*drug effects/metabolism MH - Catechin/*pharmacology MH - Cerebral Cortex/drug effects/metabolism MH - Dentate Gyrus/*drug effects/metabolism MH - Dopamine/metabolism MH - Down-Regulation MH - Hippocampus/drug effects/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Monoamine Oxidase MH - Neurogenesis/*drug effects MH - Norepinephrine/metabolism MH - Serotonin/metabolism MH - Tyrosine 3-Monooxygenase/drug effects/metabolism PMC - PMC4312829 EDAT- 2015/01/07 06:00 MHDA- 2015/09/10 06:00 PMCR- 2015/01/01 CRDT- 2015/01/07 06:00 PHST- 2014/09/07 00:00 [received] PHST- 2014/10/19 00:00 [revised] PHST- 2014/11/17 00:00 [accepted] PHST- 2015/01/07 06:00 [entrez] PHST- 2015/01/07 06:00 [pubmed] PHST- 2015/09/10 06:00 [medline] PHST- 2015/01/01 00:00 [pmc-release] AID - tp2014135 [pii] AID - 10.1038/tp.2014.135 [doi] PST - epublish SO - Transl Psychiatry. 2015 Jan 6;5(1):e493. doi: 10.1038/tp.2014.135.