Long-term omega-3 supplementation modulates behavior, hippocampal fatty acid concentration, neuronal progenitor proliferation and central TNF-α expression in 7 month old unchallenged mice.

Trent Grundy,Bernhard T Baune,Catherine Toben,Emily J Jaehne,Frances Corrigan

doi:10.3389/fncel.2014.00399

Trent Grundy, Bernhard T Baune + Show 3 more

Open Access

https://doi.org/10.3389/fncel.2014.00399

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Abstract

Dietary polyunsaturated fatty acid (PUFA) manipulation is being investigated as a potential therapeutic supplement to reduce the risk of developing age-related cognitive decline (ARCD). Animal studies suggest that high omega (Ω)-3 and low Ω-6 dietary content reduces cognitive decline by decreasing central nervous system (CNS) inflammation and modifying neuroimmune activity. However, no previous studies have investigated the long term effects of Ω-3 and Ω-6 dietary levels in healthy aging mice leaving the important question about the preventive effects of Ω-3 and Ω-6 on behavior and underlying molecular pathways unaddressed. We aimed to investigate the efficacy of long-term Ω-3 and Ω-6 PUFA dietary supplementation in mature adult C57BL/6 mice. We measured the effect of low, medium, and high Ω-3:Ω-6 dietary ratio, given from the age of 3–7 months, on anxiety and cognition-like behavior, hippocampal tissue expression of TNF-α, markers of neuronal progenitor proliferation and gliogenesis and serum cytokine concentration. Our results show that a higher Ω-3:Ω-6 PUFA diet ratio increased hippocampal PUFA, increased anxiety, improved hippocampal dependent spatial memory and reduced hippocampal TNF-α levels compared to a low Ω-3:Ω-6 diet. Furthermore, serum TNF-α concentration was reduced in the higher Ω-3:Ω-6 PUFA ratio supplementation group while expression of the neuronal progenitor proliferation markers KI67 and doublecortin (DCX) was increased in the dentate gyrus as opposed to the low Ω-3:Ω-6 group. Conversely, Ω-3:Ω-6 dietary PUFA ratio had no significant effect on astrocyte or microglia number or cell death in the dentate gyrus. These results suggest that supplementation of PUFAs may delay aging effects on cognitive function in unchallenged mature adult C57BL/6 mice. This effect is possibly induced by increasing neuronal progenitor proliferation and reducing TNF-α.

Highlights

The role of diet in the maintenance of mental health has long been recognized
Dietary interventions aimed at preventing cognitive decline have received attention, as it appears that diet across the entire lifespan plays a complex role in the development of cognitive decline (Gillette-Guyonnet et al, 2013)
Previous investigation into the mechanisms of this effect suggest that -3 polyunsaturated fatty acid (PUFA) supplementation has anti-inflammatory properties in aged mice (Labrousse et al, 2012) and increases neurogenesis in young mice (Kawakita et al, 2006), through stimulating brain derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) expression (Jiang et al, 2009; Valente et al, 2009; Bhatia et al, 2011)

Summary

Introduction

The role of diet in the maintenance of mental health has long been recognized. Evidence suggests that the typical western diet is detrimental to the maintenance of cognitive function with aging (Francis and Stevenson, 2013). Previous investigation into the mechanisms of this effect suggest that -3 PUFA supplementation has anti-inflammatory properties in aged mice (Labrousse et al, 2012) and increases neurogenesis in young mice (Kawakita et al, 2006), through stimulating brain derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) expression (Jiang et al, 2009; Valente et al, 2009; Bhatia et al, 2011). It is important to note that increased -6, or a low ratio of 3: 6, is associated with impaired cognition and behavior in animal and human studies (Loef and Walach, 2013; Van Elst et al, 2014), few studies have looked at this to date

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