Short-term administration of omega 3 fatty acids from fish oil results in increased transthyretin transcription in old rat hippocampus

Abstract

Reduced brain levels of long chain polyunsaturated fatty acids[arachidonic acid and docosahexanoic acid (DHA)] are observed in elderly subjects and patients with Alzheimer's disease. To determine the effects of n-3 fatty acids on aged rat brain, 2-year-old rats were fed fish oil (27% DHA content) for 1 month, and gene expression analysis and fatty acid and molecular species composition of the major phospholipid species were assessed. No significant alteration could be observed in the fatty acid composition of ethanolamine phosphoglycerides and phosphatidylserines with the exception of DHA, which was slightly higher in brains of rats receiving fish oil. However, a drastic reduction in arachidonic acid in phosphatidylinositoles was observed. The expression of 23 genes was altered in response to fish oil feeding in the hippocampus. The transcription of transthyretin (TTR) was induced by 10-fold as evidenced by microarray analysis and confirmed by real-time quantitative RT-PCR. Expression of IL-1 and NO synthase, which has been implicated in the prevention of neurological diseases, was unaltered. TTR is an amyloid ␤ protein scavenger, so an increase in its expression could prevent amyloid aggregate formation. We believe the beneficial effects of fish oil might be common to other agents, i.e., induce TTR expression, like nicotine and Ginkgo biloba extract.

Prevention of Alzheimer's disease: Omega-3 fatty acid and phenolic anti-oxidant interventions

“…Anti-amyloid activities include modulation of secretase activities via membrane "fluidity"/protein mobility changes or Akt > GSK regulation of ␥-secretase [25] and induction of anti-amyloidogenic transthyretin [26]. Like fish oil, DHA from algal sources can be safely taken as a supplement at high doses.…”

Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition

“…DHA can affect neural function by enhancing synaptic membrane fluidity and function (Jump, 2002), regulating gene expression (Duplus et al, 2000;Ikemoto et al, 2000;Kitajka et al, 2002;Puskas et al, 2003;Salem et al, 2001), mediating cell signaling (de Urquiza et al, 2000;Jump, 2002;Vaidyanathan et al, 1994), and enhancing long-term potentiation (McGahon et al, 1999). …”

“…Docosahexaenoic acid (DHA; C22: 6n-3), one of the major omega-3 polyunsaturated fatty acids in the brain, is important for brain development and plasticity, and provides support to learning and memory events in animal models of Alzheimer's disease (Hashimoto et al, 2002;Lim et al, 2005) and brain injury (Wu et al, 2004a). DHA can affect neural function by enhancing synaptic membrane fluidity and function (Jump, 2002), regulating gene expression (Duplus et al, 2000;Ikemoto et al, 2000;Kitajka et al, 2002;Puskas et al, 2003;Salem et al, 2001), mediating cell signaling (de Urquiza et al, 2000;Jump, 2002;Vaidyanathan et al, 1994), and enhancing long-term potentiation (McGahon et al, 1999). …”

Effects of centrally administered prostaglandin E3 and thromboxane A3 on plasma noradrenaline and adrenaline in rats: Comparison with prostaglandin E2 and thromboxane A2

“…Interestingly, these supplements have been shown to drastically reduce the levels of arachidonic acid in the hippocampus (Puskás et al, 2003). Recently, we reported the possibility that brain phosphatidylinositol-derived arachidonic acid is involved in the centrally administered histamine-induced elevation of plasma catecholamines (Shimizu et al, 2007).…”

“…Dietary supplements of fish oils rich in -3 PUFA have been reported to increase the levels of -3 PUFA (docosahexaenoic acid) in the hippocampus and forebrain of aged rats (Puskás et al, 2003;Dyall et al, 2007). Interestingly, these supplements have been shown to drastically reduce the levels of arachidonic acid in the hippocampus (Puskás et al, 2003).…”