The study of brain metabolism during aging in rats: the effect of the ketogenic diet and calorie restriction
Year: 2014
Type: dissertation
Abstract: Alzheimer’s disease is associated with a reduction of brain glucose uptake, which may be involved in the development of the cognitive problems associated with the disease. It is however unclear whether brain glucose uptake is decreased in the cognitively healthy elderly. Under conditions of glucose deficit, ketones are the alternative brain energy substrate. A mild ketosis, induced by the ketogenic diet, improves cognitive functions in animal models and humans. Our first objective was to evaluate the effect of healthy aging and of a ketogenic diet on brain glucose and ketone uptake in the rat. Brain uptake of radiotracers analogous to glucose and ketones was measured by positron emission tomography. Our results show that the uptake of the brains two main energy substrates is generally similar in healthy young and aged rats, but is higher under the ketogenic diet. The induction of a mild ketosis may compensate the reduction of brain glucose uptake occurring in Alzheimer’s disease. The second objective was to assess the effect of a ketogenic diet on brain glucose and ketone metabolism in the rat. Metabolic pathway intermediates of glucose and ketones were measured by nuclear magnetic resonance spectroscopy. Results show that glucose and ketone metabolism in brain cells is higher under the ketogenic diet. Content of [gamma]-aminobutyric acid, the main inhibitory neurotransmitter, is also higher under the ketogenic diet, which could contribute to the antiepileptic effect of the ketogenic diet. The third objective was to evaluate the effect of a long-term calorie restriction, which may induce a mild ketosis, on brain metabolism in healthy aged rats. Our results show that, in conjunction with a diet enriched in sucrose and low in omega-3 fatty acids, long-term calorie restriction in aged rats does not change brain metabolite and fatty acid profiles. Omega-3 fatty acid deficiency and an overload of sucrose may prevent the beneficial effects associated with calorie restriction in the brain.
Author: Roy, Maggie
Language: French
Topic: Diet and metabolism studies
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Université de Sherbrooke, Réseau québécois de recherche sur le vieillissement, Agence Nationale de la Recherche, Canada Research Chairs, Fonds Québécois de la Recherche sur la Nature et les Technologies, Canadian Institutes of Health Research, Fonds de Recherche du Québec - Santé, Faculty of Medicine and Health, University of Sydney
OpenAlex ID: W7198571173