Polyphenols and IUGR Pregnancies: Effects of the Antioxidant Hydroxytyrosol on Brain Neurochemistry and Development in a Porcine Model.

Natalia Yeste,Martí Pumarola,Daniel Valent,Antonio González-Bulnes,Consolación García-Contreras,Anna Bassols,Marta Vázquez-Gómez,Laura Arroyo

doi:10.3390/antiox10060884

Natalia Yeste, Martí Pumarola + Show 6 more

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https://doi.org/10.3390/antiox10060884

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Abstract

Supplementation of a mother’s diet with antioxidants, such as hydroxytyrosol (HTX), has been proposed to ameliorate the adverse phenotypes of fetuses at risk of intrauterine growth restriction. In the present study, sows were treated daily with or without 1.5 mg of HTX per kilogram of feed from day 35 of pregnancy (at 30% of total gestational period), and individuals were sampled at three different ages: 100-day-old fetuses and 1-month- and 6-month-old piglets. After euthanasia, the brain was removed and the hippocampus, amygdala, and prefrontal cortex were dissected. The profile of the catecholaminergic and serotoninergic neurotransmitters (NTs) was characterized and an immunohistochemical study of the hippocampus was performed. The results indicated that maternal supplementation with HTX during pregnancy affected the NT profile in a brain-area-dependant mode and it modified the process of neuron differentiation in the hippocampal CA1 and GD areas, indicating that cell differentiation occurred more rapidly in the HTX group. These effects were specific to the fetal period, concomitantly with HTX maternal supplementation, since no major differences remained between the control and treated groups in 1-month- and 6-month-old pigs.

Highlights

Polyphenols are the most common antioxidants found in food since they are abundant in many vegetal sources
The piglet brain is a good animal model since it is gyrencephalic and has a grey-to-white-matter ratio and a brain growth spurt in the perinatal period that is similar to humans [36,60]. These effects do not extend postnatally since no major differences between the control and HTX-supplemented groups were observed in 1-month-old and 6-month-old pigs, indicating that the continuous presence of HTX is needed to maintain its effects on the brain
Our results show that the effects of HTX were not equivalent in the three brain areas, suggesting that differences exist between HTX metabolism and cellular effects and/or its connection to the dopaminergic pathways

Summary

Introduction

Polyphenols are the most common antioxidants found in food since they are abundant in many vegetal sources. One of the most potent polyphenols is hydroxytyrosol (HTX), which is present in olive fruits (and in virgin olive oil) and is one of the main compounds responsible for the benefits of the Mediterranean diet [1]. HTX has recognized antioxidant activity and regulatory properties on metabolism, inflammation, and immuno-modulation [2,3]. HTX is absorbed, leading to biologically active concentrations in plasma, and it is metabolized in polyphenol derivatives, which have positive effects [4] and are able to cross the blood–brain barrier [5]. There is increasing clinical and epidemiological evidence on its relevance against pathologies, such as cancer, inflammatory, cardiovascular, metabolic, infectious, and neurodegenerative diseases [6,7,8,9].

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