Involvement of Microglia in Neurodegenerative Diseases: Beneficial Effects of Docosahexahenoic Acid (DHA) Supplied by Food or Combined with Nanoparticles

Abstract

Neurodegenerative diseases represent a major public health issue and require better therapeutic management. The treatments developed mainly target neuronal activity. However, an inflammatory component must be considered, and microglia may constitute an important therapeutic target. Given the difficulty in developing molecules that can cross the blood–brain barrier, the use of food-derived molecules may be an interesting therapeutic avenue. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (22:6 omega-3), has an inhibitory action on cell death and oxidative stress induced in the microglia. It also acts on the inflammatory activity of microglia. These data obtained in vitro or on animal models are corroborated by clinical trials showing a protective effect of DHA. Whereas DHA crosses the blood–brain barrier, nutritional intake lacks specificity at both the tissue and cellular level. Nanomedicine offers new tools which favor the delivery of DHA at the cerebral level, especially in microglial cells. Because of the biological activities of DHA and the associated nanotargeting techniques, DHA represents a therapeutic molecule of interest for the treatment of neurodegenerative diseases.

Western diet feeding since adolescence impairs functional hyperemia probed by functional ultrasound imaging at adulthood and middle age: rescue by a balanced ω-3:ω-6 polyunsaturated fatty acids ratio in the diet

“…Of note, in our experimental conditions, metabolic improvement induced by a balanced ω-3:ω-6 PUFAs ratio was not accompanied by weight loss. Thus, in our model, DHA is not likely to influence peripheral lipotoxicity directly but rather to contribute to local protective mechanisms in the brain 70 .…”

Docosahexaenoic Acid (DHA), Vitamin D3, and Probiotics Supplementation Improve Memory, Glial Reactivity, and Oxidative Stress Biomarkers in an Aluminum-Induced Cognitive Impairment Rat Model

“…Several studies have demonstrated that DHA limits the inflammatory effects likely due to its direct impact on the microglia. 57 The DHA treatment can restore the ramification of Iba1 + cells, influencing a morphological shift away from the amoeboid-like shape and toward the classic ramified morphology with cellular extensions protruding from the cell body with a more permissive, surveillant state. 58 Although robust studies regarding probiotics to mitigate neuroinflammation remain under research, it has been proposed that these microorganisms can be used as immunization agents to promote enhanced immunoregulation via T-reg cells, shifting the immune response toward an anti-inflammatory state.…”

“…DHA + Prob + VD3 exhibited the most significant reduction, suggesting its potential to mitigate microglial activation. Several studies have demonstrated that DHA limits the inflammatory effects likely due to its direct impact on the microglia . The DHA treatment can restore the ramification of Iba1 + cells, influencing a morphological shift away from the amoeboid-like shape and toward the classic ramified morphology with cellular extensions protruding from the cell body with a more permissive, surveillant state .…”

Anti-Inflammatory and Immune Properties of Polyunsaturated Fatty Acids (PUFAs) and Their Impact on Colorectal Cancer (CRC) Prevention and Treatment

“…Three primary types of FA exist and differ based on their saturation levels: saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) [18]. SFAs have no double bonds in their carbon atoms, while MUFAs have only one, and PUFAs have two or more [19]. The three types further harbor various physiological effects.…”