Highlights • Our work is the first to show that RvD1 and RvE1 are potent inhibitors of LPS-induced TNF-α, IL-6 and IL-1β gene expression. • RvD1 and RvE1 are modulators of microglial phenotype in ...vitro. • RvE1 regulates NFκB signaling pathway. • RvD1 regulates miRNAs expression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Omega-3 fatty acids (n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive ...reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in Humans. However, the n-3 PUFAs deficiency-mediated mechanisms affecting the development of the central nervous system are poorly understood. Active microglial engulfment of synapses regulates brain development. Impaired synaptic pruning is associated with several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development in mice. Our results show that maternal dietary n-3 PUFA deficiency increases microglia-mediated phagocytosis of synaptic elements in the rodent developing hippocampus, partly through the activation of 12/15-lipoxygenase (LOX)/12-HETE signaling, altering neuronal morphology and affecting cognitive performance of the offspring. These findings provide a mechanistic insight into neurodevelopmental defects caused by maternal n-3 PUFAs dietary deficiency.
•Dietary n-3 LC-PUFA supplementation modulates hippocampal oxylipins profile.•Dietary n-3 LC-PUFA supplementation decreases hippocampal pro-inflammatory cytokines induced by LPS.•Oxylipin profile ...depending on dietary intake could orchestrate inflammatory response to LPS.
The brain is highly enriched in long chain polyunsaturated fatty acids (LC-PUFAs) that display immunomodulatory properties in the brain. At the periphery, the modulation of inflammation by LC-PUFAs occurs through lipid mediators called oxylipins which have anti-inflammatory and pro-resolving activities when derived from n-3 LC-PUFAs and pro-inflammatory activities when derived from n-6 LC-PUFAs. However, whether a diet rich in LC-PUFAs modulates oxylipins and neuroinflammation in the brain has been poorly investigated. In this study, the effect of a dietary n-3 LC-PUFA supplementation on oxylipin profile and neuroinflammation in the brain was analyzed. Mice were given diets deficient or supplemented in n-3 LC-PUFAs for a 2-month period starting at post-natal day 21, followed by a peripheral administration of lipopolysaccharide (LPS) at adulthood. We first showed that dietary n-3 LC-PUFA supplementation induced n-3 LC-PUFA enrichment in the hippocampus and subsequently an increase in n-3 PUFA-derived oxylipins and a decrease in n-6 PUFA-derived oxylipins. In response to LPS, n-3 LC-PUFA deficient mice presented a pro-inflammatory oxylipin profile whereas n-3 LC-PUFA supplemented mice displayed an anti-inflammatory oxylipin profile in the hippocampus. Accordingly, the expression of cyclooxygenase-2 and 5-lipoxygenase, the enzymes implicated in pro- and anti-inflammatory oxylipin synthesis, was induced by LPS in both diets. In addition, LPS-induced pro-inflammatory cytokine increase was reduced by dietary n-3 LC-PUFA supplementation. These results indicate that brain n-3 LC-PUFAs increase by dietary means and promote the synthesis of anti-inflammatory derived bioactive oxylipins. As neuroinflammation plays a key role in all brain injuries and many neurodegenerative disorders, the present data suggest that dietary habits may be an important regulator of brain cytokine production in these contexts.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Providing well-being and maintaining good health are main objectives subjects seek from diet. This manuscript describes the development and preliminary validation of an instrument assessing ...well-being associated with food and eating habits in a general healthy population. Qualitative data from 12 groups of discussion (102 subjects) conducted with healthy subjects were used to develop the core of the Well-being related to Food Questionnaire (Well-BFQ). Twelve other groups of discussion with subjects with joint (n = 34), digestive (n = 32) or repetitive infection complaints (n = 30) were performed to develop items specific to these complaints. Five main themes emerged from the discussions and formed the modular backbone of the questionnaire: “Grocery shopping”, “Cooking”, “Dining places”, “Commensality”, “Eating and drinking”. Each module has a common structure: items about subject's food behavior and items about immediate and short-term benefits. An additional theme – “Eating habits and health” – assesses subjects' beliefs about expected benefits of food and eating habits on health, disease prevention and protection, and quality of ageing. A preliminary validation was conducted with 444 subjects with balanced diet; non-balanced diet; and standard diet. The structure of the questionnaire was further determined using principal component analyses exploratory factor analyses, with confirmation of the sub-sections food behaviors, immediate benefits (pleasure, security, relaxation), direct short-term benefits (digestion and satiety, energy and psychology), and deferred long-term benefits (eating habits and health). Thirty-three subscales and 14 single items were further defined. Confirmatory analyses confirmed the structure, with overall moderate to excellent convergent and divergent validity and internal consistency reliability. The Well-BFQ is a unique, modular tool that comprehensively assesses the full picture of well-being related to food and eating habits in the general population.
•A qualitative phase in healthy subjects was conducted to develop the Well-BFQ.•The Well-BFQ considers social and environmental aspects related to food.•The Well-BFQ measures immediate, short-term and long term food-related well-being.•The Well-BFQ scoring is available.•The Well-BFQ has a unique modular structure allowing specific aims to be addressed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Highlight • Our work confirmed that the concept of “resting” and “activated” microglia is misleading since microglia might present a high morpho-functional plasticity in vivo.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•Fatty acids can modulate microglia function across lifetime.•Lipids influence microglia through direct and indirect mechanisms.•Dietary lipids could represent a novel modifiable factor in diseases ...involving microglial dysfunctions.
Microglia are key players in brain function by maintaining brain homeostasis across lifetime. They participate to brain development and maturation through their ability to release neurotrophic factors, to remove immature synapses or unnecessary neural progenitors. They modulate neuronal activity in healthy adult brains and they also orchestrate the neuroinflammatory response in various pathophysiological contexts such as aging and neurodegenerative diseases. One of the main features of microglia is their high sensitivity to environmental factors, partly via the expression of a wide range of receptors. Recent data pinpoint that dietary fatty acids modulate microglia function. Both the quantity and the type of fatty acid are potent modulators of microglia physiology. The present review aims at dissecting the current knowledge on the direct and indirect mechanisms (focus on gut microbiota and hormones) through which fatty acids influence microglial physiology. We summarize main discoveries from in vitro and in vivo models on fatty acid-mediated microglial modulation. All these studies represent a promising field of research that could promote using nutrition as a novel therapeutic or preventive tool in diseases involving microglia dysfunctions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Immune-to-brain interactions are known to play a role in the pathophysiology of behavioral symptoms. Pro-inflammatory cytokines released by activated immune cells are notorious for causing ...neuropsychiatric alterations, including fatigue, decreased appetite, cognitive dysfunction and mood changes. Metabolic disorders, such as obesity, type 2 diabetes and the metabolic syndrome, are characterized by a chronic low-grade inflammatory state, with an over-expression of circulating inflammatory markers. Not surprisingly, these conditions are also associated with a high prevalence of neuropsychiatric symptoms. In order to assess the contribution of inflammation to neuropsychiatric comorbidity in these conditions, clinical studies were conducted patients with obesity, type 2 diabetes and/or the metabolic syndrome. Experimental studies in an animal model of metabolic syndrome were also implemented to further address this question. Overall, results indicate that chronically activated inflammatory processes, in conjunction with metabolic deregulations and separate vulnerability factors, are associated with neuropsychiatric symptoms and that weight loss significantly regulates these effects. These data suggest that strategies to regulate inflammation may be of particular relevance for the management of neuropsychiatric comorbidities in patients with metabolic disorders.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Obesity is a metabolic and inflammatory disorder that represents a major risk factor for development of comorbidities such as cardiovascular diseases or diabetes. Obese patients also often experience ...mood and cognitive dysfunctions, which drastically worsen obesity. Reducing their development may therefore allow improving health and quality of life of obese patients. Converging studies suggested that inflammation, which is a key component of severe obesity, might contribute to development of neuropsychiatric alterations, especially when it occurs in brain areas controlling mood and cognition such as the hippocampus. Nutrients such as n-3 polyunsaturated fatty acids (n-3 PUFAs) or antioxidants (AO) are known to improve emotional and cognitive alterations in other medical conditions, particularly by modulating neuroinflammation. However, their effect in obesity still remains poorly understood. Thus, we aimed here to evaluate if a n-3 PUFAs/AO supplemented diet improved mood and cognition in a genetic mouse model of obesity, and to identify the underlying mechanisms. Chronic supplemented diet consumption did not improve anxiety-like behavior, but reversed spatial memory deficits associated with obesity. This improvement, which occurs independently of any normalization of increased inflammation, may rather involve modulation of hippocampal neuronal plasticity. These findings suggest dissociation between the neurobiological mechanisms respectively underlying mood and cognitive alterations associated with obesity. They may help indentifying new targets for nutritional interventions aiming to improve health and quality of life of obese patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Polyunsaturated fatty acids (PUFAs) are essential fatty acids which are provided to the body through the diet. The brain is one of the richest organs in the body and has a high need in PUFAs. There ...are 2 main families of PUFAs, n-3 (or omega 3) and n-6 (or omega6). While it is quite easy to find n-6 PUFAs in westernized diets, the need in n-3 PUFAs is poorly reached, leading to decreased level of docosahexaenoic acid (DHA) in the brain. In humans, poor levels of blood n-3 PUFAs and brain DHA are associated to a higher prevalence of cognitive disorders and depression. However, the mechanisms underlying the effect of DHA on brain functions are poorly understood. Using mice models of n-3 PUFAs dietary deficiency or supplementation, we revealed that in the brain, DHA regulate neuroinflammatory pathways, in particular through its effect on microglia, the main innate immune system cell in the brain. In addition, n-3 PUFAs are key actors of ndocannabinoid- dependent synaptic plasticity. While neuroinflammation and eCB-dependent synaptic plasticity are crucial to cognition and emotional behaviour alterations, our results bring to the clinical scene the importance of controlling dietary n-3 PUFAs to protect the brain from the adverse effect of stres or inflammation. Altogether, our work brings a better comprehension of how dietary n-3 PUFAs participate to brain physiology and protect from the development of mood and cognitive disorders. It opens new avenues for the use of these lipids in the protection and treatment of brain diseases.
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Le microbiote intestinal est un acteur clé de la communication entre les intestins et le cerveau et pourrait participer à la physiopathologie de plusieurs maladies du système nerveux, dont les ...maladies neurodégénératives. Les études des liens causaux entre le microbiote et les pathologies du cerveau font apparaître l’importance de la neuro-inflammation, qui se définit par les processus inflammatoires qui se produisent au sein du cerveau. Ainsi, le microbiote et le système immunitaire cérébral jouent un rôle clé dans l’étiopathogénie des maladies neurodégénératives. Dans cette revue, nous discutons du rôle des probiotiques, de leurs effets protecteurs vis-à-vis de la neuroinflammation et de leur impact sur la prévention et le traitement des pathologies neurodégénératives.