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The endocannabinoid system and NGF are involved in the mechanism of action of resveratrol: a multi-target nutraceutical with therapeutic potential in neuropsychiatric disorders

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Abstract

Rationale

Resveratrol is a polyphenolic compound with antioxidant, anti-inflammatory, and neuroprotective effects. It has also shown antidepressant-like effects in the behavioral studies; however, its mechanism(s) of action merit further evaluation.

Objectives

The interaction between the nerve growth factor (NGF) and endocannabinoid system (eCBs) and their contribution to the antidepressant or emotional activity prompted us to evaluate their implications in the mechanism of action of resveratrol.

Methods

After single and 4-week intraperitoneal (i.p.) once-daily injections of resveratrol (40, 80, and 100 mg/kg), amitriptyline (2.5, 5, and 10 mg/kg), or clonazepam (10, 20, and 40 mg/kg) into male Wistar rats, eCB and NGF contents were quantified in the brain regions implicated in the modulation of emotions by isotope-dilution liquid chromatography/mass spectrometry and Bio-Rad protein assay, respectively. In the case of any significant alteration of brain eCB or NGF level, the effect of pre-treatment with cannabinoid CB1 or CB2 receptor antagonist (AM251 or SR144528) was investigated.

Results

Four-week treatment with resveratrol or amitriptyline resulted in a significant and sustained enhancement of NGF and eCB contents in dose-dependent and brain region-specific manner. Neither acute nor 4-week treatment with clonazepam affected brain eCB or NGF contents. Pre-treatment with AM251 (3 mg/kg), but not SR144528, prevented the enhancement of NGF protein levels. AM251 exhibited no effect by itself.

Conclusions

Resveratrol like the classical antidepressant, amitriptyline, affects brain NGF and eCB signaling under the regulatory drive of CB1 receptors.

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References

  • Abalo R, Cabezos PA, Vera G, Fernandez-pujol R, Martin MI (2010) The cannabinoid antagonist SR144528 enhances the acute effect of WIN 55,212-2 on gastrointestinal motility in the rat. Neurogastroenterol Motil 22:694–e206

    Article  CAS  PubMed  Google Scholar 

  • Ahmeda RF, Abdel-Rahmana RF, Abdallaha HMI, Saleha DO, Farid OAHA, Hessin AF (2014) Antidepressant-like effect of resveratrol in a subchronic model of depression. J Arab Soc Med Res 9:48–53

    Google Scholar 

  • Aloe L, Rocco ML, Balzamino BO, Micera A (2015) Nerve growth factor: a focus on neuroscience and therapy. Curr Neuropharmacol 13:294–303

    Article  CAS  PubMed  Google Scholar 

  • Bambico FR, Duranti A, Tontini A, Tarzia G, Gobbi G (2009) Endocannabinoids in the treatment of mood disorders: evidence from animal models. Curr Pharm Des 15:1623–1646

    Article  CAS  PubMed  Google Scholar 

  • Banasr M, Valentine GW, Li XY, Gourley SL, Taylor JR, Duman RS (2007) Chronic unpredictable stress decreases cell proliferation in the cerebral cortex of the adult rat. Biol Psychiatry 62:496–504

    Article  CAS  PubMed  Google Scholar 

  • Baumeister H, Harter M (2007) Prevalence of mental disorders based on general population surveys. Soc Psychiatry Psychiatr Epidemiol 42:537–546

    Article  PubMed  Google Scholar 

  • Berton O, Nestler EJ (2006) New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci 7:137–151

    Article  CAS  PubMed  Google Scholar 

  • Bonnafous C, Martinez J, Fargeas MJ, Buéno L (1993) Clonazepam-induced intestinal motor disturbances are linked to central nervous system release of cholecystokinin in rats. Eur J Pharmacol 237:237–242

    Article  CAS  PubMed  Google Scholar 

  • Bournival J, Quessy P, Martinoli MG (2009) Protective effects of resveratrol and quercetin against MPP+-induced oxidative stress act by modulating markers of apoptotic death in dopaminergic neurons. Cell Mol Neurobiol 29:1169–1180

    Article  CAS  PubMed  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  • Bureau G, Longpré F, Martinoli MG (2008) Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation. J Neurosci Res 86:403–410

    Article  CAS  PubMed  Google Scholar 

  • Castren E, Voikar V, Rantamaki T (2007) Role of neurotrophic factors in depression. Curr Opin Pharmacol 7:18–21

    Article  CAS  PubMed  Google Scholar 

  • Chachay VS, Macdonald GA, Martin JH, Whitehead JP, O'Moore-Sullivan TM, Lee P, Franklin M, Klein K, Taylor PJ, Ferguson M, Coombes JS, Thomas GP, Cowin GJ, Kirkpatrick CM, Prins JB, Hickman IJ (2014) Resveratrol does not benefit patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 12:2092–2103

    Article  CAS  PubMed  Google Scholar 

  • Chadwick W, Mitchell N, Caroll J, Zhou Y, Park SS, Wang L, Becker KG, Zhang Y, Lehrmann E, Wood WH, Martin B, Maudsley S (2011) Amitriptyline-mediated cognitive enhancement in aged 3 × Tg Alzheimer’s disease mice is associated with neurogenesis and neurotrophic activity. PLoS ONE 6:e21660

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cheng S, Ma M, Ma Y, Wang Z, Xu G, Liu X (2009) Combination therapy with intranasal NGF and electroacupuncture enhanced cell proliferation and survival in rats after stroke. Neurol Res 31:753–758

    Article  PubMed  Google Scholar 

  • Conner JM, Franks KM, Titterness AK, Russell K, Merrill DA, Christie BR, Sejnowski TJ, Tuszynski MH (2009) NGF is essential for hippocampal plasticity and learning. J Neurosci 29:10883–10889

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • de Lago E, Petrosino S, Valenti M, Morera E, Ortega-Gutierrez S, Fernandez-Ruiz J, Di Marzo V (2005) Effect of repeated systemic administration of selective inhibitors of endocannabinoid inactivation on rat brain endocannabinoid levels. Biochem Pharmacol 70:446–452

    Article  PubMed  Google Scholar 

  • di Matteo V, di Mascio M, di Giovanni G, Esposito E (2000) Acute administration of amitriptyline and mianserin increases dopamine release in the rat nucleus accumbens: possible involvement of serotonin 2C receptors. Psychopharmacology (Berl) 150:45–51

    Article  Google Scholar 

  • Dono LM, Currie PJ (2012) The cannabinoid receptor CB1 inverse agonist AM251 potentiates the anxiogenic activity of urocortin I in the basolateral amygdala. Neuropharmacology 62:192–199

    Article  CAS  PubMed  Google Scholar 

  • Dutta AK, Gopishetty B, Gogoi S, Ali S, Zhen J, Reith M (2011) The novel trisubstituted pyran derivative D-142 has triple monoamine reuptake inhibitory activity and exerts potent antidepressant-like activity in rodents. Eur J Pharmacol 671:39–44

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ebendal T (1992) Function and evolution in the NGF family and its receptors. J Neurosci Res 32:461–470

    Article  CAS  PubMed  Google Scholar 

  • Ereshefsky L (2009) Drug-drug interactions with the use of psychotropic medications: questions and answers. CNS Spectr 14:1–8

    PubMed  Google Scholar 

  • Fan E, Zhang L, Jiang S, Bai Y (2008) Beneficial effects of resveratrol on atherosclerosis. J Med Food 11:610–614

    Article  CAS  PubMed  Google Scholar 

  • Femenia T, Garcia-Gutierrez MS, Manzanares J (2010) CB1 receptor blockade decreases ethanol intake and associated neurochemical changes in fawn-hooded rats. Alcohol Clin Exp Res 34:131–141

    Article  CAS  PubMed  Google Scholar 

  • Erlund I, Koli R, Alfthan G, Marniemi J, Puukka P, Mustonen P, Mattila P, Jula A (2008) Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol. Am J Clin Nutr 87:323–331

    CAS  PubMed  Google Scholar 

  • Ge JF, Peng L, Cheng JQ, Pan CX, Tang J, Chen FH, Li J (2013) Antidepressant-like effect of resveratrol: involvement of antioxidant effect and peripheral regulation on HPA axis. Pharmacol Biochem Behav 114–115:64–69

    Article  PubMed  Google Scholar 

  • Gobbi G, Bambico FR, Mangieri R, Bortolato M, Campolongo P, Solinas M, Cassano T, Morgese MG, Debonnel G, Duranti A, Tontini A, Tarzia G, Mor M, Trezza V, Goldberg SR, Cuomo V, Piomelli D (2005) Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis. Proc Natl Acad Sci U S A 102:18620–18625

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gwinn RP, Kondratyev A, Gale K (2002) Time-dependent increase in basic fibroblast growth factor protein in limbic regions following electroshock seizures. Neuroscience 114:403–409

    Article  CAS  PubMed  Google Scholar 

  • Han YS, Zheng WH, Bastianetto S, Chabot JG, Quirion R (2004) Neuroprotective effects of resveratrol against β-amyloid-induced neurotoxicity in rat hippocampal neurons: involvement of protein kinase C. Br J Pharmacol 141:997–1005

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hassanzadeh P (2010) The endocannabinoid system: critical for the neurotrophic action of psychotropic drugs. Biomed Rev 21:31–46

    Article  CAS  Google Scholar 

  • Hassanzadeh P, Hassanzadeh A (2010) Effects of different psychotropic agents on the central nerve growth factor protein. Iran J Basic Med Sci 13:202–209

    CAS  Google Scholar 

  • Hassanzadeh P, Rahimpour S (2011) The cannabinergic system is implicated in the upregulation of central NGF protein by psychotropic drugs. Psychopharmacology 215:129–141

    Article  CAS  PubMed  Google Scholar 

  • Hassanzadeh P, Hassanzadeh A (2011a) Involvement of the neurotrophin and cannabinoid systems in the mechanisms of action of neurokinin receptor antagonists. Eur Neuropsychopharmacol 21:905–917

    Article  CAS  PubMed  Google Scholar 

  • Hassanzadeh P, Hassanzadeh A (2011b) The role of the endocannabinoids in suppression of the hypothalamic-pituitary-adrenal axis activity by doxepin. Iran J Basic Med Sci 14:414–421

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hassanzadeh P, Hassanzadeh A (2012) The CB1 receptor-mediated endocannabinoid signaling and NGF: the novel targets of curcumin. Neurochem Res 37:1112–1120

    Article  CAS  PubMed  Google Scholar 

  • Hassanzadeh P, Arbabi E (2012) Cannabinoid CB1 receptors mediate the gastroprotective effect of neurotensin. Iran J Basic Med Sci 15:803–810

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hassanzadeh P, Hassanzadeh A (2013) Implication of NGF and endocannabinoid signalling in the mechanism of action of sesamol: a multi-target natural compound with therapeutic potential. Psychopharmacology 229:571–578

    Article  CAS  PubMed  Google Scholar 

  • Hellweg R, Hock C, Hartun HD (1989) An improved rapid and highly sensitive enzyme immunoassay for nerve growth factor. Tech J Meth Cell Mol Biol 1:43–49

    Google Scholar 

  • Hellweg R, Thomas H, Arnswald A, von Richthofen S, Kay S, Fink H, Morgenstern R, Hörtnagl H (2001) Serotonergic lesion of median raphe nucleus alters nerve growth factor content and vulnerability of cholinergic septohippocampal neurons in rat. Brain Res 907:100–108

    Article  CAS  PubMed  Google Scholar 

  • Hellweg R, Lang UE, Nagel M, Baumgartner A (2002) Subchronic treatment with lithium increases nerve growth factor content in distinct brain regions of adult rats. Mol Psychiatry 7:604–608

    Article  CAS  PubMed  Google Scholar 

  • Hoener MC, Hewitt E, Conner JM, Costello JW, Varon S (1996) Nerve growth factor (NGF) content in adult rat brain tissues is several-fold higher than generally reported and is largely associated with sedimentable fractions. Brain Res 728:47–56

    Article  CAS  PubMed  Google Scholar 

  • Huang EJ, Reichardt LF (2001) Neurotrophins: roles in neuronal development and function. Ann Rev Neurosci 24:677–736

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hurley LL, Akinfiresoye L, Kalejaiye O, Tizabi Y (2014) Antidepressant effects of resveratrol in an animal model of depression. Behav Brain Res 268:1–7

    Article  CAS  PubMed  Google Scholar 

  • Jang SW, Liu X, Chan CB, Weinshenker D, Hall RA, Xiao G, Ye K (2009) The antidepressant amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Chem Biol 16:644–656

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Khaspekov LG, Brenz Verca MS, Frumkina LE, Hermann H, Marsicano G, Lutz B (2004) Involvement of brain-derived neurotrophic factor in cannabinoid receptor-dependent protection against excitotoxicity. Eur J Neurosci 19:1691–1698

    Article  PubMed  Google Scholar 

  • Kodali M, Parihar VK, Hattiangady B, Mishra V, Shuai B, Shetty AK (2015) Resveratrol prevents age-related memory and mood dysfunction with increased hippocampal neurogenesis and microvasculature, and reduced glial activation. Sci Rep 5(8075):1–16

    Google Scholar 

  • Koga D, Santa T, Fukushima T, Homma H, Imai K (1997) Liquid chromatographic-atmospheric pressure chemical ionization mass spectrometric determination of anandamide and its analogues in rat brain and peripheral tissues. J Chromatogr B Biomed Sci Appl 690:7–13

    Article  CAS  PubMed  Google Scholar 

  • Lad SP, Neet KE, Mufson EJ (2003) Nerve growth factor: structure, function and therapeutic implications for Alzheimer’s disease. Curr Drug Targets CNS Neurol Disord 2:315–334

    Article  CAS  PubMed  Google Scholar 

  • McLaughlin RJ, Gobbi G (2012) Cannabinoids and emotionality: a neuroanatomical perspective. Neuroscience 204:134–144

    Article  CAS  PubMed  Google Scholar 

  • Marsicano G, Lutz B (2006) Neuromodulatory functions of the endocannabinoid system. J Endocrinol Investig 29:27–46

    Article  CAS  Google Scholar 

  • Martin AR, Villegas I, Sanchez-Hidalgo M, de la Lastra CA (2006) The effects of resveratrol, a phytoalexin derived from red wines, on chronic inflammation induced in an experimentally induced colitis model. Br J Pharmacol 147:873–885

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Miwa T, Moriizumi T, Horikawa I, Uramoto N, Ishimaru T, Nishimura T, Furukawa M (2002) Role of nerve growth factor in the olfactory system. Microsci Res Tech 58:197–203

    Article  CAS  Google Scholar 

  • Moises HC, Womble MD, Washburn MS, Williams LR (1995) Nerve growth factor facilitates cholinergic neurotransmission between nucleus basalis and the amygdala in rat: an electrophysiological analysis. J Neurosci 15:8131–8142

    CAS  PubMed  Google Scholar 

  • Nemeroff CB (2007) The burden of severe depression: a review of diagnostic challenges and treatment alternatives. J Psychiatr Res 41:189–206

    Article  PubMed  Google Scholar 

  • Pacher P, Batkai S, Kunos G (2006) The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58:389–462

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Patel S, Rademacher DJ, Hillard CJ (2003) Differential regulation of the endocannabinoids anandamide and 2-arachidonylglycerol within the limbic forebrain by dopamine receptor activity. J Pharmacol Exp Ther 306:880–888

    Article  CAS  PubMed  Google Scholar 

  • Patel KR, Scott E, Brown VA, Gescher AJ, Steward WP, Brown K (2011) Clinical trials of resveratrol. Ann N Y Acad Sci 1215:161–169

    Article  CAS  PubMed  Google Scholar 

  • Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Academic, San Diego

    Google Scholar 

  • Pirola L, Frojdo S (2008) Resveratrol: one molecule, many targets. IUBMB Life 60:323–332

    Article  CAS  PubMed  Google Scholar 

  • Rodríguez-Gaztelumendi A, Rojo ML, Pazos A, Díaz A (2009) Altered CB1 receptor-signaling in prefrontal cortex from an animal model of depression is reversed by chronic fluoxetine. J Neurochem 108:1423–1433

    Article  PubMed  Google Scholar 

  • Saha L, Amitava C (2014) Understanding the anti-kindling role and its mechanism of resveratrol in pentylenetetrazole induced-kindling in a rat model. Pharmacol Biochem Behav 120:57–64

    Article  CAS  PubMed  Google Scholar 

  • Shaltiel G, Chen G, Manji HK (2007) Neurotrophic signalling cascades in the pathophysiology and treatment of bipolar disorder. Curr Opin Pharmacol 7:22–26

    Article  CAS  PubMed  Google Scholar 

  • Sun AY, Wang Q, Simonyi A, Sun GY (2010) Trans-resveratrol as a therapeutic agent for neurodegenerative diseases. Mol Neurobiol 41:375–383

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Suzuki Y, Wang L, Edge J, Mimaki T, Walson PD (1994) Anticonvulsant tolerance to clonazepam in amygdala kindled rats: clonazepam concentrations and benzodiazepine receptor binding. Neuropharmacology 33:869–874

    Article  CAS  PubMed  Google Scholar 

  • Tanis KQ, Duman RS (2007) Intracellular signaling pathways pave roads to recovery for mood disorders. Ann Med 39:531–544

    Article  CAS  PubMed  Google Scholar 

  • Timmers S, Auwerx J, Schrauwen P (2012) The journey of resveratrol from yeast to human. Aging (Albany NY) 4:146–158

    Google Scholar 

  • Tomé-Carneiro J, Larrosa M, González-Sarrías A, Tomás-Barberán FA, García-Conesa MT, Espín JC (2013) Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence. Curr Pharm Des 19:6064–6093

    Article  PubMed Central  PubMed  Google Scholar 

  • van der Made SM, Plat J, Mensink RP (2015) Resveratrol does not influence metabolic risk markers related to cardiovascular health in overweight and slightly obese subjects: a randomized, placebo-controlled crossover trial. PLoS ONE 10:e0118393

    Article  PubMed Central  PubMed  Google Scholar 

  • van der Watt G, Laugharne J, Janca A (2008) Complementary and alternative medicine in the treatment of anxiety and depression. Curr Opin Psychiatry 21:37–42

    Article  PubMed  Google Scholar 

  • Vinay P, KhanMohammad M, Alvin T, Sahebarao PM (2004) Differential effects of typical and atypical antipsychotics on nerve growth factor and choline acetyltransferase expression in the cortex and nucleus basalis of rats. J Psychiat Res 38:521–529

    Article  Google Scholar 

  • Viveros MP, Marco EM, File SE (2005) Endocannabinoid system and stress and anxiety responses. Pharmacol Biochem Behav 81:331–342

    Article  CAS  PubMed  Google Scholar 

  • Viveros MP, Marco EM, Liorente R, Lopez-Gallardo M (2007) Endocannabinoid system and synaptic plasticity: implication for emotional response. Neural Plast 2007:52908

    PubMed Central  PubMed  Google Scholar 

  • Wang Z, Gu J, Wang X, Xie K, Luan Q, Wan N, Zhang Q, Jiang H, Liu D (2013) Antidepressant-like activity of resveratrol treatment in the forced swim test and tail suspension test in mice: the HPA axis, BDNF expression and phosphorylation of ERK. Pharmacol Biochem Behav 112:104–110

    Article  PubMed  Google Scholar 

  • Williams EJ, Walsh FS, Doherty P (2003) The FGF receptor uses the endocannabinoid signaling system to couple to an axonal growth response. J Cell Biol 160:481–486

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Winkler J, Ramirez GA, Thal LJ, Waite JJ (2000) Nerve growth factor (NGF) augments cortical and hippocampal cholinergic functioning after p75NGF receptor-mediated deafferentation but impairs inhibitory avoidance and induces fear-related behaviors. J Neurosci 20:834–844

    CAS  PubMed  Google Scholar 

  • Xu Y, Wang Z, You W, Zhang X, Li S, Barish PA, Vernon MM, Du X, Li G, Pan J, Ogle WO (2010) Antidepressant-like effect of trans-resveratrol: involvement of serotonin and noradrenaline system. Eur Neuropsychopharmacol 20:405–413

    Article  CAS  PubMed  Google Scholar 

  • Yanpallewar SU, Fernandes K, Marathe SV, Vadodaria KC, Jhaveri D, Rommelfanger K, Ladiwala U, Jha S, Muthig V, Hein L, Bartlett P, Weinshenker D, Vaidya VA (2010) α2-adrenoceptor blockade accelerates the neurogenic, neurotrophic, and behavioral effects of chronic antidepressant treatment. J Neurosci 30:1096–1109

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yoshino J, Conte C, Fontana L, Mittendorfer B, Imai S, Schechtman KB, Gu C, Kunz I, Rossi Fanelli F, Patterson BW, Klein S (2012) Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. Cell Metab 16:658–664

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yu Y, Wang R, Chen C, Du X, Ruan L, Sun J, Li J, Zhang L, O'Donnell JM, Pan J, Xu Y (2013) Antidepressant-like effect of trans-resveratrol in chronic stress model: behavioral and neurochemical evidences. J Psychiatr Res 47:315–322

    Article  PubMed  Google Scholar 

  • Zhong LM, Zong Y, Sun L, Guo JZ, Zhang W, He Y, Song R, Wang WM, Xiao CJ, Lu D (2012) Resveratrol inhibits inflammatory responses via the mammalian target of rapamycin signaling pathway in cultured LPS-stimulated microglial cells. PLoS ONE 7:e32195

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was funded in part by a grant (TUMS-20270) from Tehran University of Medical Sciences, Tehran, Iran. The authors would like to thank Prof. Majid Gaffarpour, Neurological Research Center, Tehran University of Medical Sciences, for fruitful discussion. The experiments comply with the current laws of Iran.

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Correspondence to Parichehr Hassanzadeh.

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The experimental procedures were performed in accordance with the Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research and approved by the Institutional Animal Care and Use Committee.

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Hassanzadeh, P., Arbabi, E., Atyabi, F. et al. The endocannabinoid system and NGF are involved in the mechanism of action of resveratrol: a multi-target nutraceutical with therapeutic potential in neuropsychiatric disorders. Psychopharmacology 233, 1087–1096 (2016). https://doi.org/10.1007/s00213-015-4188-3

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