Glutamate export at the choroid plexus in health, thiamin deficiency, and ethanol intoxication: Review and hypothesis

Nixon, P.F. (2008) Glutamate export at the choroid plexus in health, thiamin deficiency, and ethanol intoxication: Review and hypothesis. Alcoholism Clinical and Experimental Research, 32 8: 1339-1349. doi:10.1111/j.1530-0277.2008.00727.x


Author Nixon, P.F.
Title Glutamate export at the choroid plexus in health, thiamin deficiency, and ethanol intoxication: Review and hypothesis
Journal name Alcoholism Clinical and Experimental Research   Check publisher's open access policy
ISSN 0145-6008
Publication date 2008-01-01
Year available 2008
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1111/j.1530-0277.2008.00727.x
Open Access Status DOI
Volume 32
Issue 8
Start page 1339
End page 1349
Total pages 11
Place of publication United States
Publisher Wiley-Blackwell
Language eng
Subject C1
110199 Medical Biochemistry and Metabolomics not elsewhere classified
970106 Expanding Knowledge in the Biological Sciences
Abstract 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.

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.

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 alpha-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.

Impairment of the CP by ethanol intoxication and by thiamin-deficient carbohydrate metabolism has a common, rational explanation that can guide future research.
Keyword choroid plexus
glutamate transport
glutamate receptors
ethanol intoxication
thiamin deficiency
eye
peripheral nerves
testis
review and hypothesis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: 2009 Higher Education Research Data Collection
School of Chemistry and Molecular Biosciences
 
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Created: Sat, 21 Feb 2009, 01:00:23 EST by Jennifer Falknau on behalf of School of Chemistry & Molecular Biosciences