Webinar on Cellular & Molecular Mechanisms
Sprekers: Dr. Aniko Korosi & Sophie Layé
Recorded on October 14, 2021
Early-life stress induced cognitive decline: a role for fatty acids and neuroinflmmation
Dr. Aniko Korosi, Associate Professor at Swammerdam Institute for Life Sciences, Center for Neuroscience, Brain Plasticity Group, University of Amsterdam
Clinical and pre-clinical evidence shows that early-life stress (ES) leads to cognitive impairments and increased vulnerability to develop psychopathologies later in life. However, currently no interventions exist. We have previously shown that chronic ES exposure induces cognitive decline in mice, which correlates with a reduction in hippocampal neurogenesis and more IBA1 and CD68 expressing hippocampal microglia and at four months of age compared to control mice. In addition, we recently showed that a dietary intervention with essential LCPUFA’s, with a reduced n-6/n-3 ratio (P2 – P42) can is able to prevent ES-induced cognitive decline accompanied by restoration of ES-induced reductions in hippocampal newborn cell survival and increased hippocampal CD68 expression, suggesting that the beneficial effect of the diet is mediated by modulating hippocampal neurogenesis and microglia functioning. We thus next investigated if and how ES and early dietary FAs might program the brain long-term and modulate the response to a secondary immune challenge later in life. We focused on transcriptome profile in hippocampus as well as lipidomic and SPM (specialized pro-resolving mediator) analyses in the hypothalamus at basal and in response to LPS.
We found that both diet and ES impact on the gene expression, lipidome and SPM profile of the brain and how these change in response to LPS.
Concluding, ES-induced cognitive decline can be prevented by nutritional intervention with improved lipid content and the early adveristy and diet alter long-term the brain lipid and gene expression profile in response to a secondary immune challenge. This gives new insights for the development of targeted dietary interventions for vulnerable populations.
Dietary polyunsaturated fatty acids and neuroimmune interactions, role of oxylipins
Sophie Layé, PhD, Unity Director – Team leader at Université de Bordeaux, Head of NutriNeuro
Polyunsaturated fatty acids (PUFAs) are essential fatty acids. Our organism needs them but as it cannot produce them, they are provided through the diet. The brain is one of the richest organs in the body and has a high need in PUFAs. There are 2 main families of PUFAs, n-3 (or omega 3) and n-6 (or omega6). While it is quite easy to find n-6 PUFAs in westernized diets, the need in n-3 PUFAs is poorly reached, leading to decreased level of n-3 PUFAs in the brain. Using mice models of n-3 PUFAs dietary deficiency or supplementation, we revealed that in the brain, PUFA and their derivatives, oxylipins, regulate neuroinflammatory pathways, in particular through its effect on microglia, the main innate immune system cell in the brain. While neuroinflammation is an important risk factor in cognition and emotional behaviour alterations, our results bring the importance of controlling dietary n-3 PUFAs to protect the brain from the adverse effect of inflammation. It opens new avenues for the use of these lipids in the protection and treatment of mood and cognitive disorders.