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Preventing effect of plant extracts and omega-3 on age-related cognitive decline in male mice
Marie Martin1,2, Adrien Peltier1,3, Heena Vanmalibhai Lad1
1Université Bordeaux, INRAE, Bordeaux INP, Nutrineuro, UMR 1286, 33076, Bordeaux, France.
Background:
Aging is associated with cognitive decline, accompanied by neuroinflammation, oxidative stress, impaired synaptic plasticity, and gut microbiota dysbiosis. Nutritional interventions, specifically those rich in polyphenols, carotenoids, and omega-3 (om-3) fatty acids, have demonstrated potential benefits in preventing age-related cognitive decline. This study investigates the combined effects of plant extracts (PE) including polyphenols and carotenoids, and fish oil containing om-3 on cognitive function and underlying biological processes in aged mice.
Objectives:
To assess the impact of PE and om-3, alone and in combination, on age-related cognitive decline, especially on memory outcomes and to highlight mechanisms involved in these effects.
Methods:
17-month-old male C57BL/6 J mice were divided into control and supplemented groups (PE, om-3, and PE + om-3). A group of young mice was used for positive control. Behavioral assessments, including the Elevated Plus Maze (EPM) for anxiety-like behavior, the Object Location Test (OLT) for short-term memory and the Morris Water Maze (MWM) for long-term memory, were conducted. RNA sequencing, fatty acid and oxylipin concentrations analysis and gut microbiota analysis were used to explore molecular changes and microbial diversity.
Results:
All supplementations significantly improved short-term memory in the OLT, while only PE and PE + om-3 prevented long-term memory deficits in the MWM. All supplementations modulated gene expression, reducing inflammation, apoptosis or oxidative stress markers in the hippocampus. PE + om-3 further enhanced synaptic plasticity pathways and improved microbiota composition by decreasing harmful bacteria associated with cognitive decline.
Conclusion:
Combined PE and om-3 supplementation could provide a complementary approach to combat age-related cognitive decline, highlighting its potential in promoting long-term neuroprotection through modulation of inflammation, oxidative stress and gut microbiota.

