PhD student position available in the QualiVie team

Published on 05/04/2018

Dietary lipids, membrane remodeling, and neurodegenerative risk associated with brain aging

Aging is a complex and unavoidable phenomenon which involves multiple and progressive molecular processes that can be induced by various individual and environmental factors. This phenomenon becomes pathological when it accelerates or worsens with time due to combined factors including genetic disposition and chronic or acute exposure to different environmental risk factors, including those related to lifestyle and diet. Dysregulated lipid metabolism and dyslipidemia indeed have been increasingly involved in pathological aging, thus contributing to cardiovascular and neurodegenerative diseases, Alzheimer’s in particular [1].
Several animal and human studies have reported the beneficial role of omega-3 polyunsaturated fatty acids (PUFAs) on brain function and on the prevention of age-related cognitive decline [2]. Our work and those of others have demonstrated that in the aged mouse, the neuronal membrane has undergone significant remodeling that contributes to increased susceptibility and vulnerability to neurodegenerative processes [3]. More recently, focusing on the receptor of CNTF (ciliary neurotrophic factor) as a model, we observed that such a reorganization of neuronal membranes is associated with an impaired function of this receptor in the aged mouse. These membrane rearrangements are also observed as a consequence of a saturated fatty acid-rich diet, while dietary supply of the omega-3 PUFA docosahexaenoic acid (DHA, C22:6 n-3) prevents these changes in maintaining optimal lipid environment to the membrane-associated proteins [4]. Using cell and animal models developed in our laboratory [5-7], we now seek to determine the impact of age- and/or dietary lipid-dependent neuronal membrane remodeling on other types of membrane-associated proteins such as receptors or proteins involved in neurotransmission that play important roles in neuronal functions. With this goal, we will be able (i) to determine the neuronal functions impaired by these remodeling mechanisms, (ii) to evaluate the consequences of the major Alzheimer’s disease risk factors such as age or high-fat diet on the functions of neuronal membrane proteins, and (iii) to develop preventive nutritional approaches designed to preserve neuronal membrane protein functionality despite these risk factors.
The results obtained from this PhD thesis project should provide important information on the mechanisms to explain the link between aging and susceptibility to neurodegeneration, and in doing so, allow us to define the conditions required to preserve therapeutic target functions and pathways in aged individuals. The results obtained here could then lead to the design of new innovative and more efficient approaches to treat and/or prevent Alzheimer’s disease.

For more information : http://rp2e.univ-lorraine.fr/index.php?id=5