Depletion of dietary phytoestrogens reduces hippocampal plasticity and contextual fear memory stability in adult male mouse

Introduction: Phytoestrogens are non-steroidal estrogen analogues and are found primarily in soy products. They have received increasing attention as dietary supplements for estrogen deficiency and as modulators of endogenous estrogen functions, including cognition and emotion. In addition to modify...

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Published in:Nutritional neuroscience 2021-12, Vol.24 (12), p.951-962
Main Authors: Çalışkan, Gürsel, Raza, Syed Ahsan, Demiray, Yunus E., Kul, Emre, Sandhu, Kiran V., Stork, Oliver
Format: Article
Language:English
Subjects:
Animals
Behavior, Animal
contextual fear memory
Diet
dorsal hippocampus
equol
Equol - pharmacology
Fear - physiology
Hippocampus - drug effects
Hippocampus - physiology
Long-Term Potentiation - drug effects
Long-Term Potentiation - physiology
LTD
LTP
Male
Memory - drug effects
Memory - physiology
Mice
Mice, Inbred C57BL
Neuronal Plasticity - drug effects
Neuronal Plasticity - physiology
NR2B
Phosphorylation - physiology
Phytoestrogens
Phytoestrogens - administration & dosage
Receptors, N-Methyl-D-Aspartate - physiology
Synapses - physiology
synaptic plasticity
ventral hippocampus
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Summary:Introduction: Phytoestrogens are non-steroidal estrogen analogues and are found primarily in soy products. They have received increasing attention as dietary supplements for estrogen deficiency and as modulators of endogenous estrogen functions, including cognition and emotion. In addition to modifying the levels of circulating sex hormones, phytoestrogens also exert direct effects on estrogen and androgen receptors in the brain and thus effectively modulate the neural circuit functions. Objective: The aim of this study was to investigate the long-term effects of low phytoestrogen intake (∼6 weeks) on the hippocampal plasticity and hippocampus-dependent memory formation in the adult C57BL/6 male mice. Methods and Results: In comparison to mice on a diet with normal phytoestrogen content, mice on low phytoestrogen diet showed a significant reduction in the phosphorylation of NR2B subunit, a molecular correlate of plasticity in the Schaffer collateral-CA1 synapse. We observed a profound decrease in long-term potentiation (LTP) in the ventral hippocampus, whereas no effect on plasticity was evident in its dorsal portion. Furthermore, we demonstrated that acute perfusion of slices with an estrogen analogue equol, an isoflovane metabolized from daidzein produced by the bacterial flora in the gut, was able to rescue the observed LTP deficit. Examining potential behavioral correlates of the plasticity attenuation, we found that mice on phytoestrogen-free diet display decreased contextual fear memory at remote but not at recent time points after training. Conclusions: Our data suggests that nutritional phytoestrogens have profound effects on the plasticity in the ventral hippocampus and ventral hippocampus-dependent memory.
ISSN:1028-415X
1476-8305
DOI:10.1080/1028415X.2019.1698826