Abstract
Regular consumption of food enriched in omega3 polyunsaturated fatty acids (ω3 PUFAs) has been shown to reduce risk of cognitive decline in elderly, and possibly development of Alzheimer's disease. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are the most likely active components of ω3-rich PUFAs diets in the brain. We therefore hypothesized that exposing mice to a DHA and EPA enriched diet may reduce neuroinflammation and protect against memory impairment in aged mice. For this purpose, mice were exposed to a control diet throughout life and were further submitted to a diet enriched in EPA and DHA during 2 additional months. Cytokine expression together with a thorough analysis of astrocytes morphology assessed by a 3D reconstruction was measured in the hippocampus of young (3-month-old) and aged (22-month-old) mice. In addition, the effects of EPA and DHA on spatial memory and associated Fos activation in the hippocampus were assessed. We showed that a 2-month EPA/DHA treatment increased these long-chain ω3 PUFAs in the brain, prevented cytokines expression and astrocytes morphology changes in the hippocampus and restored spatial memory deficits and Fos-associated activation in the hippocampus of aged mice. Collectively, these data indicated that diet-induced accumulation of EPA and DHA in the brain protects against neuroinflammation and cognitive impairment linked to aging, further reinforcing the idea that increased EPA and DHA intake may provide protection to the brain of aged subjects.
Highlights
A decline in memory and cognitive functions, likely to rely on hippocampal dysfunction, is considered to be a normal consequence of aging [1]
Male offspring were fed with the same diet as their dam until they were 1 month or 20 months old; thereafter, they were either maintained on the control diet or changed on an isocaloric LCv3 PUFAsupplemented diet containing a mixture of rapeseed oil, high-oleic sunflower oil, palm oil and tuna oil resulting in a 10% eicosapentaenoic acid (EPA) and 7% Docosahexaenoic acid (DHA) diet (LCv3 diet) for 2 additional months
Post-hoc analysis further revealed a significant increase of EPA and DHA in the brain of aged mice fed with the fish oil diet as compared to those fed with the control diet (p,0.001)
Summary
A decline in memory and cognitive functions, likely to rely on hippocampal dysfunction, is considered to be a normal consequence of aging [1]. In adult and aged rodents, these cytokines alter long-term potentiation (LTP), a cellular model of synaptic plasticity that has often been argued to play a role in learning and memory [20,21,22]. Inhibition of microglial activation and cytokines production by minocycline restores hippocampal LTP in aged rats [24] and improves memory in an animal model of Alzheimer’s disease [25]. All together, these findings support the idea that neuroinflammation is a decisive component of cognitive disorders in aged subjects
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