Nutrient transport systems in brain: 40 years of progress

In the last 40 years, especially with the application of new neurochemical and molecular biologic techniques, there has been an explosive progress in understanding how nutrients are transported across the blood-brain barrier and choroid plexus into brain and CSF, and how nutrient homeostasis in brain is achieved. In most cases, there are separate transporters, or in a few cases, systems that transport related substances (e.g., biotin, lipoic, and pantothenic acids). This review focuses on three crucial nutrients (glucose, ascorbic acid, and folates) for which there is substantial new information including 'knock down' and 'knockout' models in mice and/or humans. The overall objective is to show that this new knowledge leads not just to a more thorough understanding (e.g., of 'why' questions like: why do neurons require up to 10 mM ascorbic acid intracellulary?); but in some cases leads to clinically important predictions that allow treatment of heretofore devastating neurologic disorders.