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Issue 8, 2021
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Stimulatory effects of (−)-epicatechin and its enantiomer (+)-epicatechin on mouse frontal cortex neurogenesis markers and short-term memory: proof of concept

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Abstract

Consumption of (−)-epicatechin (Epi), a cacao flavanol improves cognition. The aim was to compare the effects of (−)-Epi or its stereoisomer (+)-Epi on mouse frontal cortex-dependent short-term working memory and modulators of neurogenesis. Three-month-old male mice (n = 7 per group) were provided by gavage either water (vehicle; Veh), (−)-Epi, at 1 mg kg−1 or (+)-Epi at 0.1 mg per kg of body weight for 15 days. After treatment, spontaneous alternation was evaluated by Y-maze. Brain frontal cortex was isolated for nitrate/nitrite measurements, Western blotting for nerve growth factor (NGF), microtubule associated protein 2 (MAP2), endothelial and neuronal nitric oxide synthase (eNOS and nNOS) and immunohistochemistry for neuronal specific protein (NeuN), doublecortin (DCX), capillary (CD31) and neurofilaments (NF200). Results demonstrate the stimulatory capacity of (−)-Epi and (+)-Epi on markers of neuronal proliferation as per increases in immunoreactive cells for NeuN (74 and 120% respectively), DCX (70 and 124%) as well as in NGF (34.4, 63.6%) and MAP2 (41.8, 63.8%). Capillary density yielded significant increases with (−)-Epi (∼80%) vs. (+)-Epi (∼160%). CD31 protein levels increased with (−)-Epi (∼70%) and (+)-Epi (∼140%). Effects correlated with nitrate/nitrite stimulation by (–)-Epi and (+)-Epi (110.2, 246.5%) and enhanced eNOS phosphorylation (Ser1177) with (–)-Epi and (+)-Epi (21.4, 41.2%) while nNOS phosphorylation only increased with (+)-Epi (18%). Neurofilament staining was increased in (–)-Epi by 135.6 and 84% with (+)-Epi. NF200 increased with (–)-Epi (116%) vs. (+)-Epi (84.5%). Frontal cortex-dependent short-term spatial working improved with (–)-Epi and (+)-Epi (15, 13%). In conclusion, results suggest that both enantiomers, but more effectively (+)-Epi, upregulate neurogenesis markers likely through stimulation of capillary formation and NO triggering, improvements in memory.

Graphical abstract: Stimulatory effects of (−)-epicatechin and its enantiomer (+)-epicatechin on mouse frontal cortex neurogenesis markers and short-term memory: proof of concept

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Article information


Submitted
23 Nov 2020
Accepted
04 Mar 2021
First published
26 Mar 2021

Food Funct., 2021,12, 3504-3515
Article type
Paper

Stimulatory effects of (−)-epicatechin and its enantiomer (+)-epicatechin on mouse frontal cortex neurogenesis markers and short-term memory: proof of concept

V. Navarrete-Yañez, A. Garate-Carrillo, M. Ayala, A. Rodriguez-Castañeda, P. Mendoza-Lorenzo, G. Ceballos, R. Ordoñez-Razo, S. Dugar, G. Schreiner, F. Villarreal and I. Ramirez-Sanchez, Food Funct., 2021, 12, 3504
DOI: 10.1039/D0FO03084H

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