Roles of the Unsaturated Fatty Acid Docosahexaenoic Acid in the Central Nervous System: Molecular and Cellular Insights

Abstract

Fatty acids (FAs) are essential components of the central nervous system (CNS), where they exert multiple roles in health and disease. Among the FAs, docosahexaenoic acid (DHA) has been widely recognized as a key molecule for neuronal function and cell signaling. Despite its relevance, the molecular pathways underlying the beneficial effects of DHA on the cells of the CNS are still unclear. Here, we summarize and discuss the molecular mechanisms underlying the actions of DHA in neural cells with a special focus on processes of survival, morphological development, and synaptic maturation. In addition, we examine the evidence supporting a potential therapeutic role of DHA against CNS tumor diseases and tumorigenesis. The current results suggest that DHA exerts its actions on neural cells mainly through the modulation of signaling cascades involving the activation of diverse types of receptors. In addition, we found evidence connecting brain DHA and ω-3 PUFA levels with CNS diseases, such as depression, autism spectrum disorders, obesity, and neurodegenerative diseases. In the context of cancer, the existing data have shown that DHA exerts positive actions as a coadjuvant in antitumoral therapy. Although many questions in the field remain only partially resolved, we hope that future research may soon define specific pathways and receptor systems involved in the beneficial effects of DHA in cells of the CNS, opening new avenues for innovative therapeutic strategies for CNS diseases.

Understanding the Role of Oxidative Stress, Neuroinflammation and Abnormal Myelination in Excessive Aggression Associated with Depression: Recent Input from Mechanistic Studies

“…It is suggested that these interventions should be considered as integral parts of MDD treatment, particularly in cases of its co-morbidity with substance use and alcohol dependence [ 169 ]. Another established therapy was proposed by clinical studies that revealed positive effects of the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), antioxidant and anti-inflammatory agents, in patients with depression and impulsivity [ 266 , 267 ]. Deprivation of dietary n-3 polyunsaturated fatty acid, a known antioxidant, has been found to increase both depression and aggressive behaviour in rats [ 268 ].…”

Integrated untargeted and targeted metabolomics to reveal therapeutic effect and mechanism of Alpiniae oxyphyllae fructus on Alzheimer’s disease in APP/PS1 mice

“…Palmitic acid and stearic acid have been proven to increase amyloid protein in cortical neurons and promote tau hyperphosphorylation. DHA (Bazan et al, 2011;Petermann et al, 2022) and EPA (Shahidi, 2018) are unique polyunsaturated fatty acids, which can regulate synaptic function and improve salient transmission, and have great significance in neurodegenerative diseases. BAs eliminate liver cholesterol, a crucial factor in AD.…”

Evidence on docosahexaenoic acid and arachidonic acid supplementation for preterm infants

“…It is therefore not known to what extent individual LC-PUFA concentrations reflect the content of these fatty acids in tissues, particularly in the brain. Studies in isolated cell systems have shown that precursors of DHA are transferred from plasma to astrocytes, where they are converted to DHA before they are taken up by neurons [7]. This pathway of DHA synthesis in the central nervous system appears to occur in vivo in some animal species, but it is not known to what extent this occurs in humans.…”