Glutamate Export at the Choroid Plexus in Health, Thiamin Deficiency, and Ethanol Intoxication: Review and Hypothesis

• Published in: Alcoholism, clinical and experimental research Vol. 32; no. 8; pp. 1339 - 1349
• Main Author: Nixon, Peter F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2008; Lippincott Williams & Wilkins
• Subjects: Alcoholic Intoxication - metabolism; Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Choroid Plexus; Choroid Plexus - metabolism; Disease Models, Animal; Ethanol - metabolism; Ethanol Intoxication; Eye; Glucose - metabolism; Glutamate Receptors; Glutamate Transport; Glutamates - blood; Glutamates - cerebrospinal fluid; Glutamates - metabolism; Humans; Medical sciences; Peripheral Nerves; Rats; Review and Hypothesis; Testis; Thiamin Deficiency; Thiamine Deficiency - metabolism; Toxicology; Choroid plexus; Testis; Peripheral nerve; Peripheral Nerves; Central nervous system; B-Vitamins; Glutamate receptor; Review; Testicle; Hypothesis; Eye; Visual system; Alcoholic beverage; Glutamate Receptors; Thiamin Deficiency; Thiamine; Ependymal organ; Ethanol; Health; Deficiency; Glutamate; Male genital system; Ethanol Intoxication; Glutamate Transport; Review and Hypothesis; Excitatory aminoacid; Neurotransmitter; Poisoning; Transport; Bibliographic review
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/j.1530-0277.2008.00727.x

Introduction:  The earliest observed effect in the pathogenesis of experimental Wernicke’s encephalopathy and of ethanol intoxication in rats is impairment of the blood cerebrospinal fluid (CSF) barrier at the choroid plexus (CP). For an explanation, these observations direct attention to the role of the CP in maintaining glutamate homeostasis in the CSF. Methods:  Characteristics of the CP epithelium (CPE) are reviewed, focusing on its role in removal of glutamate from the CSF and its potential for impairment by ethanol oxidation or by thiamin‐deficient glucose oxidation. Results:  The export of glutamate from CSF to blood at the CP is energy dependent, saturable, and stereospecific. However, the incapacity of the CP to convert glutamate to other metabolites makes it vulnerable to glutamate accumulation should α‐ketoglutarate dehydrogenase activity be decreased. Elsewhere ethanol metabolism and thiamin‐deficiency independently decrease the activity of this mitochondrial enzyme. We argue that they have the same effect within the mitochondria‐rich CPE, thereby decreasing energy production necessary for export of glutamate from CSF to blood; diverting its energy metabolism to further glutamate production; and impairing its blood CSF barrier function. This impairment appears to be mediated by glutamate and is attenuated by MK801 but whether it involves one of the CPE glutamate receptors is yet uncertain. This impairment exposes the CSF and hence the paraventricular brain extracellular fluid to neuroactive substances from the blood, including further glutamate, explaining the paraventricular location of neuropathology in Wernicke’s encephalopathy. Other organs normally protected from blood by a barrier are affected also by ethanol abuse and by thiamin deficiency, namely the eye, peripheral nerves, and the testis. Much less is known regarding the function of these barriers. Conclusions:  Impairment of the CP by ethanol intoxication and by thiamin‐deficient carbohydrate metabolism has a common, rational explanation that can guide future research.