Nutrient transport systems in brain: 40 years of progress

Abstract

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.

Glucose promotes resistance in lymphocytes against oxidative stress-induced apoptosis through signaling and metabolic pathways. Implications for Parkinson’s disease

“…60 mM G) to neuron cells (approx. 30 mM G) via the GLUT-3 transporter (48). Recent data suggest that dysregulation of G metabolism might represent an early metabolic biomarker of sporadic PD (6).…”

Morphogens and blood-brain barrier function in health and disease

“…Vice versa, brain endothelial cells have highly efficient and specific transporter systems to provide the brain with its essential nutrients. 2 Various essential metabolitesincluding hexoses, amino acids, monocarboxylic acids, purines, nucleosides, amines, and ions -selectively enter the brain to meet the high demands of the neurons. In particular, glucose transporter -1 (GLUT-1), which actively transports glucose into the brain, is highly expressed at BBB endothelial cells.…”

“…In addition, claudin 3, claudin 5 and possibly claudin 12 also belong to the TJ proteins, as do the junctional adhesion molecules (JAMs). Similar to the AJ proteins, TJ proteins of adjacent endothelial cells connect to each other and interact with several cytoplasmic proteins, including zona occludens (ZO) proteins [1][2][3], that link the junction proteins with the endothelial cytoskeleton, further tightening the barrier (Fig. 1).…”

Antioxidant Vitamins and Their Use in Psychiatry

“…[49] Beyine Taşınması, Kan-Beyin Bariyerini Geçme Mekanizmaları Askorbik asit konsantrasyonu memelilerde plazma, beyin omurilik sıvısı (BOS) ve tüm beyinde sırası ile yaklaşık olarak 0.05, 0.2 ve 1mM'dır. [48] Koroid pleksusta bulunan askorbik asite oldukça özgül olan aktif taşıma sistemi, beyinde askorbik asit için olan homeostatik mekanizmanın bileşenlerin-den biridir. Bu durumda plazmadaki askorbik asit düzeyleri düştüğünde kandan BOS'a göreceli olarak daha fazla askorbik asit pompalanır.…”

“…Fakat damar içine verilebilecek dehidroaskorbik asit ise kan-beyin bariyerindeki GLUT1 aracılığı ile beyne girerek beyin askorbik asit konsantrasyonlarını yükseltebilir. [48] SVCT2, beyinde yoğun olarak eksprese edilen tek askorbik asit taşıyıcısıdır. [40] Askorbik asit, koroid pleksus epitel hücresinin basolateral membranındaki aktif SVCT-2 taşıyıcısı ile kandan hücre içine alınır ve bilinmeyen bir taşıyıcı ile BOS'a salınır.…”