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      Omega-3 Fatty Acids from Fish Oil Lower Anxiety, Improve Cognitive Functions and Reduce Spontaneous Locomotor Activity in a Non-Human Primate

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          Abstract

          Omega-3 (ω3) polyunsaturated fatty acids (PUFA) are major components of brain cells membranes. ω3 PUFA-deficient rodents exhibit severe cognitive impairments (learning, memory) that have been linked to alteration of brain glucose utilization or to changes in neurotransmission processes. ω3 PUFA supplementation has been shown to lower anxiety and to improve several cognitive parameters in rodents, while very few data are available in primates. In humans, little is known about the association between anxiety and ω3 fatty acids supplementation and data are divergent about their impact on cognitive functions. Therefore, the development of nutritional studies in non-human primates is needed to disclose whether a long-term supplementation with long-chain ω3 PUFA has an impact on behavioural and cognitive parameters, differently or not from rodents. We address the hypothesis that ω3 PUFA supplementation could lower anxiety and improve cognitive performances of the Grey Mouse Lemur ( Microcebus murinus), a nocturnal Malagasy prosimian primate. Adult male mouse lemurs were fed for 5 months on a control diet or on a diet supplemented with long-chain ω3 PUFA (n = 6 per group). Behavioural, cognitive and motor performances were measured using an open field test to evaluate anxiety, a circular platform test to evaluate reference spatial memory, a spontaneous locomotor activity monitoring and a sensory-motor test. ω3-supplemented animals exhibited lower anxiety level compared to control animals, what was accompanied by better performances in a reference spatial memory task (80% of successful trials vs 35% in controls, p<0.05), while the spontaneous locomotor activity was reduced by 31% in ω3-supplemented animals (p<0.001), a parameter that can be linked with lowered anxiety. The long-term dietary ω3 PUFA supplementation positively impacts on anxiety and cognitive performances in the adult mouse lemur. The supplementation of human food with ω3 fatty acids may represent a valuable dietary strategy to improve behavioural and cognitive functions.

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          Omega-3 fatty acids and monoamine neurotransmission.

          We proposed several years ago that the behavioral effects of n-3 PUFA deficiency observed in animal models might be mediated through the dopaminergic and serotonergic systems that are very involved in the modulation of attention, motivation and emotion. We evaluated this hypothesis in an extended series of experiments on rats chronically diet-deficient in alpha-linolenic acid, the precursor of long-chain n-3 PUFA, in which we studied several parameters of these neurotransmission systems. The present paper synthesizes the main data we obtained on interactions between n-3 PUFA status and neurotransmission in animal models. We demonstrated that several parameters of neurotransmission were affected, such as the vesicular pool of dopamine and serotonin, thus inducing several regulatory processes such as modification of cerebral receptors in specific brain areas. We also demonstrated that (i) a reversal diet with adequate n-6 and n-3 PUFA given during the lactating period to rats originating from alpha-linolenic acid-deficient dams was able to restore both the fatty acid composition of brain membranes and several parameters of the dopaminergic and serotonergic neurotransmission, and (ii) when given from weaning, this reversal diet allowed partial recovery of biochemical parameters, but no recovery of neurochemical factors. The occurrence of profound n-3 PUFA deficiency during the lactating period could therefore be an environmental insult leading to irreversible damage to specific brain functions. Strong evidence is now showing that a profound n-3 PUFA experimental deficiency is able to alter several neurotransmission systems, at least the dopaminergic and serotonergic. Whether these experimental findings can be transposed to human pathophysiology must be taken cautiously, but reinforces the hypothesis that strong links exist between the PUFA status, aspects of brain function such as neurotransmission processes and behavior.
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            Rapid and convenient separation of phospholipids and non phosphorus lipids from rat heart using silica cartridges

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              Cognitive Performances Are Selectively Enhanced during Chronic Caloric Restriction or Resveratrol Supplementation in a Primate

              Effects of an 18-month treatment with a moderate, chronic caloric restriction (CR) or an oral supplementation with resveratrol (RSV), a potential CR mimetic, on cognitive and motor performances were studied in non-human primates, grey mouse lemurs (Microcebus murinus). Thirty-three adult male mouse lemurs were assigned to three different groups: a control (CTL) group fed ad libitum, a CR group fed 70% of the CTL caloric intake, and an RSV group (RSV supplementation of 200 mg.kg−1.day−1) fed ad libitum. Three different cognitive tests, two motor tests, one emotional test and an analysis of cortisol level were performed in each group. Compared to CTL animals, CR or RSV animals did not show any change in motor performances evaluated by rotarod and jump tests, but an increase in spontaneous locomotor activity was observed in both groups. Working memory was improved by both treatments in the spontaneous alternation task. Despite a trend for CR group, only RSV supplementation increased spatial memory performances in the circular platform task. Finally, none of these treatments induced additional stress to the animals as reflected by similar results in the open field test and cortisol analyses compared to CTL animals. The present data provided the earliest evidence for a beneficial effect of CR or RSV supplementation on specific cognitive functions in a primate. Taken together, these results suggest that RSV could be a good candidate to mimic long-term CR effects and support the growing evidences that nutritional interventions can have beneficial effects on brain functions even in adults.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                7 June 2011
                : 6
                : 6
                : e20491
                Affiliations
                [1 ]Mécanismes Adaptatifs et Evolution, UMR 7179 Centre National de la Recherche Scientifique, Muséum National d'Histoire Naturelle, Brunoy, France
                [2 ]Laboratoire de Nutrition et Régulation Lipidique des Fonctions Cérébrales, INRA de Jouy en Josas, Domaine de Vilvert, Jouy en Josas, France
                Pontifical Catholic University of Rio Grande, Brazil
                Author notes

                Conceived and designed the experiments: JMA PG FA FP. Performed the experiments: NV MJ FP. Analyzed the data: NV ALD JMA PG FA FP. Contributed reagents/materials/analysis tools: MJ PG FA FP. Wrote the paper: ALD MJ JMA PG FA FP.

                Article
                PONE-D-11-05854
                10.1371/journal.pone.0020491
                3110190
                21666750
                d3dbf9d5-8152-47a5-a345-a6fff8f7f631
                Vinot et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 23 March 2011
                : 27 April 2011
                Page count
                Pages: 8
                Categories
                Research Article
                Biology
                Neuroscience
                Behavioral Neuroscience
                Cognitive Neuroscience
                Medicine
                Nutrition

                Uncategorized
                Uncategorized

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