Omega‐3 fatty acids reverse age‐related decreases in nuclear receptors and increase neurogenesis in old rats

Abstract

Retinoic acid receptors (RARs), retinoid X receptors (RXRs), and peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in many cellular processes, such as learning and memory. RAR and RXR mRNA levels decrease with ageing, and the decreases can be reversed by retinoic acid treatment, which also alleviates age-related memory deficits. The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have neuroprotective effects in the aged brain and are endogenous ligands of RXR and PPAR. We investigated whether dietary EPA and DHA supplementation reverses age-related declines in protein levels of these receptors in rat forebrain. Two studies were conducted comparing adult and old rats. In the first, old rats were fed standard or EPA/DHA-enriched (270 mg/kg/day, EPA to DHA ratio 1.5:1) diets for 12 weeks. Analysis by Western blot revealed significant decreases in RARa, RXRa, RXRb, and PPARg in the forebrain with ageing, which were reversed by supplementation. Immunohistochemical analysis of the hippocampus showed significant agerelated decreases in RARa and RXRb expression in CA1 and the dentate gyrus, which were restored by supplementation. Decreases in hippocampal doublecortin expression were also partially alleviated, suggesting a positive effect on neurogenesis. We also investigated the effects of DHA supplementation (300 mg/kg/day for 12 weeks) on RARa, RXRa, and RXRb expression in the prefrontal cortex, striatum, and hippocampus. Overall, DHA supplementation appeared to increase receptor expression compared with the untreated old group. These observations illustrate additional mechanisms that might underlie the neuroprotective effects of omega-3 fatty acids in ageing. V V C 2010 Wiley-Liss, Inc.

Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways

“…Furthermore, our work does not preclude synergistic/parallel effects on other signalling pathways. For example, the positive effect of omega-3 PUFA supplementation on neurogenesis in aging occur in parallel with restorative effects on the retinoic acid receptors, RARalpha and RXRbeta in CA1 and dentate gyrus regions of the hippocampus, suggesting some of the effects may be mediated by activity at these transcription factors (Dyall et al, 2010), or interaction between p38 MAPK and retinoid signalling (Piskunov and Rochette-Egly, 2012).…”

Docosahexaenoic Acid for Selective Prevention of Posttraumatic Stress Disorder Among Severely Injured Patients

“…50 These results suggest that DHA is necessary but not sufficient for regulating postnatal neural stem/progenitor cells under physiological conditions but that ARA is sufficient to affect postnatal neural stem/progenitor cells even under physiological conditions. 51 Taken together, these results suggest that for patients with extremely low DHA levels, DHA might have a beneficial effect on preventing PTSD through hippocampal neurogenesis.…”

Krill-derived Phospholipids Rich in n-3 Fatty Acid Improve Spatial Memory in Adult Rats

“…Recently, it was reported that age-related decreases in the levels of nuclear receptors, for example, retinoid X receptors or retinoic acid receptors, were reversed by supplementation of EPA and DHA in rats. Interestingly, these reversals appear only partial in rats supplemented with DHA alone (Dyall et al, 2010). These reports suggest that ingestion of both EPA and DHA is more effective than ingestion of DHA alone for the maintenance of CNS functions.…”