Chronic Silymarin, Quercetin and Naringenin Treatments Increase Monoamines Synthesis and Hippocampal Sirt1 Levels Improving Cognition in Aged Rats
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Polyphenols have beneficial neurological effects delaying cognitive and motor decline in aging due to their antioxidant, antiinflammatory and neuroprotective properties. These effects could be related to SIRT1 activation (implicated in synaptic plasticity, memory and inflammation) and monoaminergic synthesis modulation. In this work, we studied in old male rats, the in vivo effects of long-term administration of different polyphenols (silymarin, quercetin and naringenin; 20 mg/kg/day i.p, 4 weeks) (Sprague-Dawley, 18 months) on cognition and motor coordination. We also analyzed in different brain regions: tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activities, which mediate central monoaminergic neurotransmitters synthesis; and immunoreactivities of SIRT1 and NF-κB (total and acetylated forms). Results indicated that chronic polyphenolic treatments showed restorative effects on cognition and motor coordination consistently with the biochemical and molecular results. Polyphenols reversed the age-induced deficits in monoaminergic neurotransmitters (serotonin, noradrenaline, and dopamine), increasing TPH and TH activity. In addition, polyphenolic treatments increased SIRT1 levels and decreased NF-κB levels in hippocampus. These results confirm polyphenolic treatments as a valuable potential therapeutic strategy for attenuating inflamm-aging and brain function decline.
KeywordsAging Cognition Polyphenols Monoamine synthesis SIRT1 NF-κb
Authors thank the financial contribution of: Universitat de les Illes Balears (UIB)-Govern Balear (ECT 025 09), Pont La Caixa-UIB Program (7/2014) and MINECO, Madrid, Spain (SAF2014-55903-R). F. Sarubbo was supported by a UIB predoctoral contract and MR Ramis was supported by a predoctoral FPU Spanish Ministry of Education fellowship.
Compliance with Ethical Standards
The authors declare that they have no conflicts of interest, they have been informed, and consent to manuscript publication.
Human and Animal Rights
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the Bioethical Committee of the University of the Balearic Islands and with the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Directive 86/609/EEC).
- Della-Morte D, Dave KR, DeFazio RA, Bao YC, Raval AP, Perez-Pinzon MA. (2009) Resveratrol pretreatment protects rat brain from cerebral ischemic damage via a sirtuin 1-uncoupling protein 2 pathway. Neuroscience 159(3):993–1002. doi: 10.1016/j.neuroscience.2009.01.017
- Flowers A, Lee JY, Acosta S, Hudson C, Small B, Sanberg CD, Bickford PC. (2015) NT-020 treatment reduces inflammation and augments Nrf-2 and Wnt signaling in aged rats. J Neuroinflammation. 12(1):174Google Scholar
- Herskovits AZ, Guarente L. (2014) SIRT1 in neurodevelopment and brain senescence. Neuron 81(3):471–483Google Scholar
- Khan M, Khan M, Khan A, Ahmed ME, Ishrat T, Tabassum R, Vaibhav K, Ahmad A, Islam F (2012) Naringenin ameliorates Alzheimer’s disease (AD)-type neurodegeneration with cognitive impairment (AD-TNDCI) caused by the intracerebroventricular - streptozotocin in rat model. Neurochem Int 61:1081–1093CrossRefPubMedGoogle Scholar
- Michán S, Li Y, Chou M, Parrella E, Ge H, Long J, Allard J, Lewis K, Miller M, Xu W, Mervis R, Chen J, Guerin K, Smith L, McBurney M, Sinclair D, Baudry M, de Cabo R, Longo V (2010) SIRT1 is essential for normal cognitive function and synaptic plasticity. J Neurosci 30:9695–9707CrossRefPubMedPubMedCentralGoogle Scholar
- Moranta D, Esteban S, García-Sevilla J (2009) Chronic treatment and withdrawal of the cannabinoid agonist WIN 55,212-2 modulate the sensitivity of presynaptic receptors involved in the regulation of monoamine syntheses in rat brain. Naunyn Schmiedeberg's Arch Pharmacol 379:61–72CrossRefGoogle Scholar
- Qin W, Yang T, Ho L, Zhao Z, Wang J, Chen L, Zhao W, Thiyagarajan M, MacGrogan D, Rodgers J, Puigserver P, Sadoshima J, Deng H, Pedrini S, Gandy S, Sauve A, Pasinetti G (2006) Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. J Biol Chem 281:21745–21754CrossRefPubMedGoogle Scholar
- Tilstra J, Robinson A, Wang J, Gregg S, Clauson C, Reay D, Nasto L, St Croix C, Usas A, Vo N, Huard J, Clemens P, Stolz D, Guttridge D, Watkins S, Garinis G, Wang Y, Niedernhofer L, Robbins P (2012) NF-κB inhibition delays DNA damage-induced senescence and aging in mice. J Clin Invest 122:2601–2612CrossRefPubMedPubMedCentralGoogle Scholar