Basic nutritional investigationEffects of olive polyphenols administration on nerve growth factor and brain-derived neurotrophic factor in the mouse 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.
References (70)
Olive oil and the cardiovascular system
Pharmacol Res
(2007)- et al.
Modulation of cognition and behavior in aged animals: role for antioxidant- and essential fatty acid-rich plant foods
Am J Clin Nutr
(2009) - et al.
Environmental influences on brain neurotrophins in rats
Pharmacol Biochem Behav
(2002) - et al.
Stress and nerve growth factor: findings in animal models and humans
Pharmacol Biochem Behav
(2002) - et al.
Early exposure to ethanol or red wine and long-lasting effects in aged mice. A study on nerve growth factor, brain-derived neurotrophic factor, hepatocyte growth factor, and vascular endothelial growth factor
Neurobiol Aging
(2012) - et al.
Early exposure to ethanol but not red wine at the same alcohol concentration induces behavioral and brain neurotrophin alterations in young and adult mice
Neurotoxicology
(2009) - et al.
Hepatocyte growth factor, vascular endothelial growth factor, glial cell-derived neurotrophic factor and nerve growth factor are differentially affected by early chronic ethanol or red wine intake
Toxicol Lett
(2009) - et al.
p75 and Trk: a two-receptor system
Trends Neurosci
(1995) - et al.
Strain differences in mouse response to odours of predators
Behav Processes
(1994) - et al.
Green tea polyphenols prevent toxin-induced hepatotoxicity in mice by down-regulating inducible nitric oxide-derived prooxidants
Am J Clin Nutr
(2004)
Determination of 3, 4-dihydroxyphenylglycol, hydroxytyrosol and tyrosol purified from olive oil by-products with HPLC in animal plasma and tissues
Food Chemistry
Infection with Schistosoma mansoni in mice induces changes in nociception and exploratory behavior
Physiol Behav
Single episode of maternal deprivation and adult depressive profile in mice: interaction with cannabinoid exposure during adolescence
Behav Brain Res
Rita Levi-Montalcini: the discovery of nerve growth factor and modern neurobiology
Trends Cell Biol
Neurotrophin expression in the adult olfactory epithelium
Brain Res
Fighting in the aged male mouse increases the expression of TrkA and TrkB in the subventricular zone and in the hippocampus
Behav Brain Res
NOX1/NADPH oxidase negatively regulates nerve growth factor-induced neurite outgrowth
Free Radic Biol Med
All in a sniff: olfaction as a model for active sensing
Neuron
The main olfactory system and social learning in mammals
Behav Brain Res
Adult neurogenesis and the olfactory system
Prog Neurobiol
Brain NGF and EGF administration improves passive avoidance response and stimulates brain precursor cells in aged male mice
Physiol Behav
Neuroprotective and ameliorative actions of polyunsaturated fatty acids against neuronal diseases: implication of fatty acid-binding proteins (FABP) and G protein-coupled receptor 40 (GPR40) in adult neurogenesis
J Pharmacol Sci
Green tea polyphenol epigallocatechin-3-gallate signaling pathway through 67-kDa laminin receptor
J Biol Chem
Improved method for identifying and quantifying olive oil phenolic compounds and their metabolites in human plasma by microelution solid-phase extraction plate and liquid chromatography-tandem mass spectrometry
J Chromatogr B Analyt Technol Biomed Life Sci
A new hydroxytyrosol metabolite identified in human plasma: hydroxytyrosol acetate sulphate
Food Chem
Antioxidant activity of olive polyphenols in humans: a review
Int J Vitam Nutr Res
Olive leaf extract attenuates cardiac, hepatic, and metabolic changes in high carbohydrate-, high fat-fed rats
J Nutr
In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: a randomized controlled trial
Faseb J
The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial
Ann Intern Med
Virgin olive oil polyphenol hydroxytyrosol acetate inhibits in vitro platelet aggregation in human whole blood: comparison with hydroxytyrosol and acetylsalicylic acid
Br J Nutr
Beneficial effects of combined olive oil ingestion and acute exercise on postprandial TAG concentrations in healthy young women
Br J Nutr
In-vitro gastric cancer prevention by a polyphenol-rich extract from olives through induction of apoptosis
Eur J Cancer Prev
Extra virgin olive oil improves learning and memory in SAMP8 mice
J Alzheimers Dis
Effect of brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 on functional recovery and regeneration after spinal cord injury in adult rats
J Neurotrauma
Trophic factors: an evolutionary cul-de-sac or door into higher neuronal function?
J Neurosci Res
Cited by (76)
Blueberry juice augments exercise-induced neuroprotection in a Parkinson's disease model through modulation of GDNF levels
2022, IBRO Neuroscience ReportsAlcohol as an early life stressor: epigenetics, metabolic, neuroendocrine and neurobehavioral implications
2020, Neuroscience and Biobehavioral ReviewsAntioxidant properties of plant polyphenols in the counteraction of alcohol-abuse induced damage: Impact on the Mediterranean diet
2020, Journal of Functional FoodsCitation Excerpt :In this framework, bioactive compounds, like polyphenols, capable of regulating the expression of neurotrophins or their receptors can be a promising tool in the management of neurodegenerative conditions (Carito et al., 2016). Indeed, in a mouse model, intraperitoneal administration of a blend of hydroxytyrosol and other polyphenols from olive pomace caused an increase in NGF, BDNF, TrkA and TrkB levels in the brain, especially in the hippocampus and olfactory lobes (De Nicoló et al., 2013). In fact, the olfactory bulbs are crucial brain areas as the olfaction is the key sense that allows rodents to exchange information with the surrounding environment (Sanchez-Andrade & Kendrick, 2009).
Exploring the multimodal role of phytochemicals in the modulation of cellular signaling pathways to combat age-related neurodegeneration
2020, Science of the Total EnvironmentCitation Excerpt :In the animal model of depression, olive polyphenols increased the expression of both TrkA and TrkB, as well as also show antidepressant effects. Interestingly, these effects are reported in the hippocampus but not in striatum and frontal cortex (De Nicoló et al., 2013). Concomitantly, in mouse AD model, epigallocatechin gallate enhances the expression of BDNF, TrkA, TrkB, and protects the pathological alterations during AD progression.
Vagus nerve stimulation and Neurotrophins: a biological psychiatric perspective
2020, Neuroscience and Biobehavioral ReviewsOxidative stress inhibition by resveratrol in alcohol-dependent mice
2020, NutritionCitation Excerpt :Between dietary components, antioxidants are considered of interest in the context of alcohol-related disorders. We recently demonstrated in mice that polyphenols (i.e., organic molecules of natural origin) are widely present in the plant reign and produce beneficial effects to counteract damage induced by chronic ethanol consumption owing to their antioxidant and antiinflammatory properties [27–31]. Resveratrol (i.e., 3,5,4′-trihydroxy-trans-stilbene) is a nonflavonoid phenol and one of the phytoalexins that are naturally produced by several plants (Table 1) as a defensive mechanism against pathogenic agents.
Sara De Nicoló, Luigi Tarani, Mauro Ceccanti, Andrea Vania, George N. Chaldakov, and Marco Fiore planned the experimental protocols. Sara De Nicoló, Mariateresa Maldini, Fausta Natella, and Marco Fiore performed the experiments.