N-3 polyunsaturated fatty acid and neuroinflammation in aging and Alzheimer’s disease

Abstract

The innate immune system of the brain is mainly composed of microglial cells, which play a key role in the maintenance of synapses and the protection of neurons against noxious agents or lesions owing to their phagocytic activity. In the healthy brain, microglia are highly motile and strongly interact with neurons either by physical contact, induction of oxidative stress or through specific mediators, such as chemokines and cytokines. In response to inflammatory insult however, microglial cells get activated and produce inflammatory cytokines. The action of cytokines on specific receptors expressed in the brain triggers the development of sickness behavior and altered cognitive and emotional processes. The effects are acute and reversible as normal behavior is restored once the synthesis of inflammatory brain cytokines returns to baseline after a few hours. However, in pathological situations, these cytokines may reach toxic levels and have irreversible consequences such as neuronal death, as observed in neurodegenerative disorders such as Alzheimer's disease. Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are essential nutrients and fundamental components of neuronal and glial cell membranes. They accumulate in the brain during the perinatal period in a dietary supply-dependent fashion. Their brain levels may diminish with age, but can be increased by diets enriched in n-3 PUFAs. Changes in the immune profile have been associated with n-3 PUFAs intake in humans and animal models. Therefore, the increasing exposure of the population to diets low in n-3 PUFAs could contribute to the deleterious effects of the chronic activation of microglia in the brain.

Lipid and Lipoprotein Metabolism in Microglia

“…While mammals cannot synthesize n-3 PUFAs, they are available from the diet in the form of essential FAs, such as alpha-linolenic acid (ALA). n-3 PUFAs are associated with a range of benefits: from preventing age related cognitive decline to preventing metabolic syndrome and improving cardiovascular risk factors (Schwinkendorf et al, 2011;Layé et al, 2015;Trépanier et al, 2016). In contrast, omega-6 (n-6) PUFAs, which have their last double bond 6 atoms away from the terminal methyl group, are generally associated with the worsening of many chronic diseases such as obesity, neuroinflammatory diseases, and asthma (Simopoulos, 2016;Brigham et al, 2019).…”

Hedonic Eating and the “Delicious Circle”: From Lipid-Derived Mediators to Brain Dopamine and Back

“…The survival of all cells depends on fatty acids (FAs) that deliver energy supply and provide maintenance of the integrity of structural membranes. Particularly in the brain, FAs are present in enormous quantity, playing a key role as signaling molecules involved in neural development and defense against neuroinflammation and neurodegenerative disorders (Farooqui et al, 2007 ; Layé et al, 2015 ; Chianese et al, 2017 ). Acting as signaling molecules and sensors of whole-body energy status, FAs can modify the hypothalamic control of energy homeostasis (e.g., nutrient storage and mobilization) (Moullé et al, 2014 ).…”

Antioxidant Effect of Plants Aqueous Extract on Lipid Stability of <i>Oreochromis niloticus</i> during Traditional Sun and Smoke Drying in Far-North Cameroon

“…Polyunsaturated fatty acids like eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid are involved in regulating biosynthesis of prostaglandin and promoting healing of wounds. EPA, DHA and arachidonic acid can also protect human against several problems such as artherosclerosis, diabetes, cardiovascular diseases and mood disorder [3].…”