Importantly, these alterations are not uniform across the brain. Because higher cognitive functions require large—scale interactions across prefrontal cortical and hippocampal networks, selectively targeting an alteration within one region may not broadly restore function to improve cognition. One mechanism for decline that the PFC and HPC share, however, is a reduced ability to utilize glucose for energy metabolism. Thus, the current study used a ketogenic diet KD as a global metabolic strategy for improving brain function in young and aged rats. After 12 weeks, rats were trained to perform a spatial alternation task through an asymmetrical maze, in which one arm was closed and the other was open. Both young and aged KD-fed rats showed resilience against the anxiogenic open arm, training to alternation criterion performance faster than control animals. At the completion of behavioral testing, tissue punches were collected from the PFC for biochemical analysis. These data suggest that KDs could be optimal for enhancing large-scale network function that is critical for higher cognition. Advanced agemultiple is associated with declines across cognitive domains, including episodic memory Grady et al.
The ketogenic diet has been in clinical use for over 80 years, primarily for the symptomatic treatment of epilepsy. A recent clinical study has raised the possibility that exposure to the ketogenic diet may confer long-lasting therapeutic benefits for patients with epilepsy. As the underlying mechanisms become better understood, it will be possible to develop alternative strategies that produce similar or even improved therapeutic effects without the need for exposure to an unpalatable and unhealthy, high-fat diet. The ketogenic diet is a high-fat content diet in which carbohydrates are nearly eliminated so that the body has minimal dietary sources of glucose. Fatty acids are thus an obligatory source of cellular energy production by peripheral tissues and also the brain. During high rates of fatty acid oxidation, large amounts of acetyl-CoA are generated. These exceed the capacity of the tricarboxylic acid cycle and lead to the synthesis of the three ketone bodies within liver mitochondria.
Future perspectives At the present time our understanding of the effect of ketosis on behavior and cognition is still rudimentary, despite the clear reproducibility of its therapeutic efficacy. These studies illustrate that careful attention should be paid to the intricacies of the diet such as measuring ketones and calculating macronutrient ratios to fully examine its efficacy in bipolar disorder, as well as the need for larger well-designed placebo-controlled studies in this area. Chang et al. This is a subjective assessment but based on explicit criteria defined a priori given in the paper. Long-term glucose consumption, however, can exacerbate insulin resistance and metabolic syndrome. Depression in epilepsy. Schizophrenia hallucinations and paranoia started at age 14; diagnosed at age The choice platforms each contained two food wells 2. Future research should include long-term, prospective, randomized, placebo-controlled crossover dietary trials to examine the effect of KD in various mental disorders. Ketone bodies are, however, a principal source of energy during early postnatal development Nehlig,