Elsevier

Nutrition

Volume 29, Issue 4, April 2013, Pages 681-687
Nutrition

Basic nutritional investigation
Effects of olive polyphenols administration on nerve growth factor and brain-derived neurotrophic factor in the mouse brain

https://doi.org/10.1016/j.nut.2012.11.007Get rights and content

Abstract

Objective

Polyphenols are chemicals derived from plants known to possess antioxidant and anti-inflammatory properties. High intake of fruit and vegetables is believed to be beneficial to human health. Various studies have suggested that dietary polyphenols may protect against cancer and cardiometabolic and neurodegenerative diseases. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are neurotrophins that play key roles in brain cell development, growth, and survival. The aim of this study was to investigate whether or not administration of olive (Olea europaea L.) polyphenols could have an effect on NGF and BDNF content and the expression of their receptors, TrkA and TrkB, respectively, in the mouse brain.

Methods

NGF and BDNF were measured by enzyme-linked immunosorbent assay. TrkA and TrkB were measured by Western blotting.

Results

We found NGF and BDNF elevation in the hippocampus and olfactory bulbs and a decrease in the frontal cortex and striatum. These data were associated with potentiated expression of TrkA and TrkB in the hippocampus and olfactory bulbs but no differences between groups in the striatum and frontal cortex. Polyphenols did not affect some behavioral mouse parameters associated with stressing situations.

Conclusions

Altogether, this study shows that olive polyphenols in the mouse may increase the levels of NGF and BDNF in crucial areas of the limbic system and olfactory bulbs, which play a key role in learning and memory processes and in the proliferation and migration of endogenous progenitor cells present in the rodent brain.

Introduction

Olive oil, an important component of the Mediterranean diet, is known to possess antioxidant effects, probably due to oleic acid and polyphenols such as oleuropein and hydroxytyrosol [1]. Half of the phenolic compounds contained in olive leaves, olives, and virgin olive oil are hydroxytyrosol and its derivatives. Hydroxytyrosol is the major olive polyphenol consumed and well absorbed in humans. It is considered to have the highest antioxidant potency compared with other olive polyphenols. Experimental findings have shown that olive leaf extract attenuates cardiac, hepatic, and metabolic changes in high carbohydrate-, high-fat–fed rats [2]. In humans, the role of dietary olive oil in preventing cardiometabolic diseases has been proposed [3], [4]. It also inhibits in vitro platelet aggregation in human whole blood [5]. In humans, olive polyphenols decreased the plasma levels of oxidized-low-density lipoprotein and positively affected several biomarkers of oxidative damage (reviewed in [6]). It also has been shown that ingestion of olive oil may be beneficial in reducing postprandial triglyceride concentrations when associated with physical exercise [7]. An in vitro study showed that methanol extract from olives, rich in phenolic compounds, exhibits gastric cancer preventive efficacy by limiting cell proliferation, inducing cell death, and suppressing inflammation in stomach cancer cells [8]. Extra virgin olive oil also may improve learning and memory in a mouse model of Alzheimer's disease [9], [10], acting as a neuroprotective agent.

Neuroprotection in mammals is finely regulated by neurotrophic factors [11], [12]. Neurotrophic factors are proteins that stimulate the neuronal survival, development, and functions [13], [14]. Neurotrophic factors act by preventing the associated neuron from initiating programmed cell death, thus allowing the neurons to survive [13]. Neurotrophic factors also induce differentiation of progenitor cells to form neurons, a process known as neurogenesis [15], [16], [17]. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are the best studied neurotrophic factors [12], [18], [19]. NGF and BDNF play a crucial role in the survival and development of specific peripheral and brain neurons [14], [19]. Both are produced and released by a variety of cells localized in the central and peripheral nervous systems and by cells of the immune and endocrine systems [20], [21]. NGF and BDNF also play key roles in the fine-tuning of learning and memory performances and in some behavioral processes associated with stress situations [22], [23], [24], including exposure to ethanol [25]. In particular we have shown that prenatal ethanol in the mouse may disrupt brain NGF and BDNF levels; however, these changes were reduced when ethanol was administered as red wine [24], [25], [26]. We discussed these findings as an effect of the antioxidant “protective” properties of the polyphenols contained in the red wine.

Thus the aim of the present study was to investigate whether or not administration of polyphenols per se may have an effect on NGF and BDNF in the hippocampus, frontal cortex, striatum, and olfactory bulbs of the brain of CD-1 adult male laboratory mice. We also studied the NGF and BDNF receptors, TrkA and TrkB, respectively, in the same brain areas [27], [28], [29]. For this purpose, we administered for 10 d a blend of 10 mg/kg of polyphenols extracted from olive residues (pomace) obtained following olive pressing in the preparation of extra virgin olive oil. Extract obtained from olive pressing residues is particularly rich in polyphenols (see Methods section). We also measured mouse blood reduced glutathione level (GSH) for assessing oxidative stress [30], the levels of hydroxytyrosol in the serum, and some behavioral parameters for investigating possible toxic effects of polyphenol administration on pain sensitivity and anxiety as the hot-plate and the Porsolt forced swimming tests.

Section snippets

Animals and polyphenols administration

CD-1 outbred male mice were housed singly in Plexiglas cages (33 × 13 × 14 cm) under standardized conditions with pellet food (enriched standard diet purchased from Mucedola, Settimo Milanese, Italy). A 12L:12D lighting regime was used. CD-1 outbred mice were used because this strain shares some aspects with the Mus musculus mouse living in nature and because the CD-1 strain is one of the most common mouse strains used for behavioral studies [31], [32]. Animals were divided in two groups,

Effects on mouse body weight, food and water consumption, hot-plate, forced-swim test, and serum hydroxytyrosol

Data showed that there were no differences between groups in body weight on all days examined. Furthermore, food and water daily consumption during polyphenol administration was also unaffected. ANOVA also revealed that polyphenols administration in CD-1 male mice had no effect on pain sensitivity on the hot-plate or in stress response in the forced-swim test (data not shown). HPLC findings showed that hydroxytyrosol and hydroxytyrosol sulphates were present in the serum of

Discussion

To our knowledge, this is the first study to demonstrate in a mouse model that a mixture of polyphenols extracted from olive pomace, obtained in the process of extra virgin olive oil production, may have effects on NGF/BDNF levels in selected brain areas. We found that polyphenols may increase NGF in the hippocampus and olfactory bulbs but decrease NGF in the frontal cortex and striatum. BDNF also was elevated in the hippocampus and olfactory bulbs, but was depleted in the frontal cortex. These

Acknowledgments

Sara De Nicolò, George Chaldakov and Marco Fiore were supported by CNR. Mariateresa Maldini and Fausta Natella were supported by INRAN. Luigi Tarani, Andrea Vania, and Mauro Ceccanti were supported by La Sapienza Università di Roma.

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