Omega-3 Polyunsaturated Fatty Acid Eicosapentaenoic Acid or Docosahexaenoic Acid Improved Ageing-Associated Cognitive Decline by Regulating Glial Polarization

Abstract

Neuroinflammation induced by microglial and astrocyte polarizations may contribute to neurodegeneration and cognitive impairment. Omega (n)-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory and neuroprotective effects, but conflicting results were reported after different n-3 PUFA treatments. This study examined both the change in glial polarizations in ageing rats and the differential effects of two omega-3 PUFAs. The results showed that both PUFAs improved spatial memory in ageing rats, with docosahexaenoic acid (DHA) being more effective than eicosapentaenoic acid (EPA). The imbalance between microglial M1/M2 polarizations, such as up-regulating IBA1 and down-regulating CD206 and arginase-1 (ARG-1) was reversed in the hippocampus by both n-3 PUFAs, while the DHA effect on CD206 was stronger. Astrocyte A1 polarization presented increasing S100B and C3 but decreasing A2 parameter S100a10 in the ageing brain, which were restored by both PUFAs, while DHA was more effective on S100a10 than EPA. Consistent with microglial M1 activation, the concentration of proinflammatory cytokines tumor necrosis factor-(TNF) α, interleukin (IL)-1β and IL-6 were significantly increased, which were attenuated by DHA, while EPA only suppressed IL-6. In correlation with astrocyte changes, brain-derived neurotrophic factor precursor was increased in ageing rats, which was more powerfully down-regulated by DHA than EPA. In summary, enhanced microglial M1 and astrocytic A1 polarizations may contribute to increased brain proinflammatory cytokines, while DHA was more powerful than EPA to alleviate ageing-associated neuroimmunological changes, thereby better-improving memory impairment.

Gut–brain communication mediates the impact of dietary lipids on cognitive capacity

“…190 EPA and DHA are able to improve cognitive problems by inhibiting neuroinflammation caused by the overactivation of M1 microglia, decreasing the expression of C3 in the brain, and the proBDNF/p75 pathway. 2…”

“…1 It has been reported that n-3 polyunsaturated fatty acids (n-3 PUFAs), as essential lipids, significantly alleviate memory impairments. 2 Conversely, mice fed a high saturated fat diet have been observed to exhibit significant cognitive decline. 3 Distinct dietary lipids exert diverse impacts on cognition and brain health.…”

Marine-Derived Anticancer Agents Targeting Apoptotic Pathways: Exploring the Depths for Novel Cancer Therapies

“…Marine algae are rich in polyunsaturated fatty acids (PUFAs), with omega-3 polyunsaturated fatty acids (ω-3 PUFAs) as their main constituent [ 255 ]. The ω-3 PUFAs are essential for regulating the structural features of immune and neural cellular membranes [ 256 ]. The two main forms of ω-3 polyunsaturated fatty acids (PUFAs) that are produced by marine algae are the long-chained 22:6n-3 docosahexaenoic acid (DHA) 37 ( Figure 7 ) and 20:5n-3 eicosapentaenoic acid (EPA) 38 ( Figure 7 ), as well as its precursor alpha-linolenic acid (ALA) 39 ( Figure 7 ) [ 257 ].…”

Dietary and Metabolic Approaches for Treating Autism Spectrum Disorders, Affective Disorders and Cognitive Impairment Comorbid with Epilepsy: A Review of Clinical and Preclinical Evidence

“…However, there are several preclinical studies in healthy and disease model animals. In healthy and aged rodents, diets supplemented with PUFAs improved their performance on several tests of memory, including spatial, object recognition, and associative memory [ 151 , 152 , 153 ]. DHA supplements seem to be more efficacious than EPA in improving memory and attenuating the proinflammatory cytokines associated with ageing [ 152 ].…”