Docosahexaenoic acid, 22:6n‐3: Its roles in the structure and function of the brain

Abstract

Docosahexaenoic acid,22:6n-3 (DHA) and its metabolites are vital for the structure and functional brain development of the fetus and infants, and also for maintenance of healthy brain function of adults. DHA is thought to be an essential nutrient required throughout the life cycle for the maintenance of overall brain health. The mode of actions of DHA and its derivatives at both cellular and molecular levels in the brain are emerging. DHA is the major prevalent fatty acid in the brain membrane. The brain maintains its fatty acid levels mainly via the uptake of plasma free fatty acids. Therefore, circulating plasma DHA is significantly related to cognitive abilities during ageing and is inversely associated with cognitive decline. The signaling pathways of DHA and its metabolites are involved in neurogenesis, antinociceptive effects, anti-apoptotic effect, synaptic plasticity, Ca 2+ homeostasis in brain diseases, and the functioning of nigrostriatal activities. Mechanisms of action of DHA metabolites on various processes in the brain are not yet well known. Epidemiological studies support a link between low habitual intake of DHA and a higher risk of brain disorders. A diet characterized by higher intakes of foods containing high in n-3 fatty acids, and/or lower intake of n-6 fatty acids was strongly associated with a lower Alzheimer's Disease and other brain disorders. Supplementation of DHA improves some behaviors associated with attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and impulsive behavior, as well as cognition. Nevertheless, the outcomes of trials with DHA supplementation have been controversial. Many intervention studies with DHA have shown an apparent benefit in brain function. However, clinical trials are needed for definitive conclusions. Dietary deficiency of n-3 fatty acids during fetal development in utero and the postnatal state has detrimental effects on cognitive abilities. Further research in humans is required to assess a variety of clinical outcomes, including quality of life and mental status, by supplementation of DHA.

Maternal dietary fatty acids and their roles in human placental development

“…In contrast, n-3 fatty acids and their eicosanoid derivatives mostly promote anti-inflammatory, anti-cancer, and anti-angiogenic activities. LCPUFAs also play essential roles in the development of the central nervous system, visual acuity, and cognitive functions [2,13,14]. Fatty acids and their ligands such as peroxisome proliferator-activated receptors (PPARs) can regulate expression of genes involved in fatty acids synthesis and oxidation, lipogenesis, glucose utilization, and insulin sensitivity, thermoregulation, energy partitioning, reverse cholesterol transport, cholesterol synthesis, low-density-lipoprotein-receptor expression, growth and differentiation, and inflammatory responses [15][16][17][18] [19,20].…”

Developmental Exposure to Silver Nanoparticles Leads to Long Term Gut Dysbiosis and Neurobehavioral Alterations

“…Unsaturated fatty acids, in particular docosahexaenoic acid (DHA), are essential for normal cognitive functions including learning and memory, coping with stress, regulating other emotional response, inhibiting inflammation in the brain, reducing the risk of impulsive disorders, AD, and other brain disorders. [109][110][111] The findings thus suggest that NP-induced changes, including enrichment of select bacteria, may correspondingly affect metabolic pathways. Changes in such pathways may serve as one mechanism linking gut microbiome to neurobehavioral alterations.…”

Does Maternal Arachidonic Acid Influence the Neurodevelopmental Effects of Docosahexaenoic Acid?

“…DHA is thought to be an essential nutrient required throughout the life cycle to maintain overall brain health. As a polyunsaturated n-3 fatty acids family member, DHA is an important and indispensable fatty acid for human health that can be sourced from marine fish and oils [27]. Also consumed plant oil sourced n-3 fatty acid, α-linolenic acid,18;3n-3 (ALA) or marine sourced eicosapentaenoic acid,20:5n-3 (EPA) can be converted into DHA in a small amount.…”

“…DHA levels are decreased in apoptotic neurological disorders, including Alzheimer's and Parkinson's diseases. Dietary DHA deficiency may lead to inflammatory conditions, cognitive disorders, insufficient neurogenesis, defective neurotransmitter metabolism, insufficient brain growth, and development [27,33]. DHA's mode of action and its derivatives at both cellular and molecular levels in the brain are emerging.…”

“…Though precise molecular mechanisms are not well defined, DHA and its bioactive derivatives play various essential functions in the brain [12,27,28]. High DHA levels in the phospholipids of synaptic membranes provide membrane flexibility and improve the efficiency of protein-protein interaction necessary for signal transduction [27]. Different aspects of metabolism, structure-function of the brain depend on optimum ARA and DHA levels and interactions between their metabolites [29].…”