Project: A menu for brain responses opposing stress-induced alterations in cognition

Duration 01/04/2016 - 31/03/2019
Project Topic Diet and nutritional habits significantly impact on brain fitness, mental and cognitive health throughout life. The relative abundance of specific dietary nutrients, depending on intake, bioavailability and metabolism, affects mental health and cognitive ability via direct and indirect mechanisms that modulate neuronal function and synaptic plasticity. Optimum nutrition is a key determinant in the well-being of the healthy ageing population world-wide, as ageing is characterized by a decline in metabolism and homeostatic processes as well as age-related cognitive impairment over time, leading to functional decline and increased risk for disease. Chronic stress has been shown to negatively impact brain plasticity and cognitive performance, in particular in the ageing brain. Interestingly, the aged brain resembles the stressed brain on both behavioural and cellular levels and stress-induced cognitive alterations are likely to be more marked in the elderly. Likewise, poor nutritional habits are hypothesized to correlate with a heightened stress reactivity and susceptibility and greater cognitive decline in elderly, supporting the notion that interactions between nutritional factors and stress susceptibility represent critical determinants of cognitive performance and age-related cognitive decline. This proposal investigates how diet through stress-related mechanisms affects cognition across the lifespan using preclinical and clinical approaches. Particular focus will be on the influence of nutrition on increased susceptibility for stress-induced cognitive deficits in memory and executive functioning from adulthood to old age (aim 1) and the impact of a nutritional intervention on cognitive ability, stress vulnerability and stress perception (aim 2). Next, the molecular mechanisms by which targeted nutritional interventions can improve stress-induced vulnerabilities in cognition will be investigated using preclinical models (aim 3). Throughout the 3 aims, the gut microbiota will be investigated as a novel critical signalling mediator between nutritional intake, stress susceptibility and maintenance of cognitive health in ageing (using samples from aims 1, 2 and 3). Elucidating the cellular and molecular mechanisms and pathways through which nutrition can promote the resistance of neurons to insults and enhance mental fitness will help us to determine how best to modulate diet composition in order to attenuate stress vulnerability, reduce susceptibility to metabolic disorders, and ultimately promote brain health during healthy ageing.
Project Results
(after finalisation)
The consortium identified that short-chain fatty acids, Ω-3 fatty acid-rich and docosahexanoic acid (DHA) rich supplementation have anti-inflammatory properties reversing stress-induced deficits in behaviour and cognitive performance. The beneficial effect on cognitive behaviour, stress and weight reduction was furthermore associated with changes in specific gut bacteria composition. Identified individuals susceptible to cognitive decline or stress (e.g. those with higher cortisol levels) could be prophylactically treated with a diet positively modulating the microbiome resulting in reduced inflammatory markers, decreased cognitive impairments and thereby in healthier aging.
Network JPI HDHL

Project partner

Number Name Role Country
1 University College Cork Coordinator Ireland
1 King’s College London Coordinator United Kingdom
2 Institut National de la Recherche Agronomique Partner France
3 German Center for Neurodegenerative Diseases (DZNE) Partner Germany
4 Drug Research and Child Health (NEUROFARBA) Partner Italy
5 University of Maastricht Partner Netherlands