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

Nixon, P.G.F.

doi:10.1111/j.1530-0277.2008.00727.x

Cited by 13 publications

(18 citation statements)

References 111 publications

(129 reference statements)

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“…Finally, the lingula lies in close proximity to the choroids plexus in the fourth ventricle. Alcohol appears to rapidly affect the choroids plexus and disrupt the blood-CSF-brain barrier, resulting in enhanced exposure to neuroactive substances (81). Hence, the vermis may be a component of a neural circuit modulating risk for substance abuse.…”

Section: Discussionmentioning

confidence: 99%

Cerebellar Lingula Size and Experiential Risk Factors Associated with High Levels of Alcohol and Drug Use in Young Adults

Anderson¹,

Rabi²,

Lukas³

et al. 2009

Cerebellum

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Previous studies have reported cerebellar abnormalities or static ataxia associated with risk for chronic use of alcohol and drugs. Adverse childhood experience (ACE) is another strong risk factor for later substance abuse. We therefore, sought to ascertain the relationship between morphological phenotypes of the lingula (Lobule I) of the anterior cerebellar vermis (ACV), and exposure to emotional (EM) versus physical (PM) maltreatment,on the degree of ongoing alcohol or drug use. The study design consisted of a cross-sectional in vivo neuroimaging study, utilizing retrospective assessment of maltreatment history and self-reports of alcohol and substance use. Study participants were 153 subjects (54M/99F, 21.9±2.2 years) selected for imaging from a database of 1,402 community participants 18–25 years of age, who completed a detailed online screening instrument, and met rigorous inclusion/exclusion criteria. Subjects were exposed to only physical abuse or harsh corporal punishment (PM group, n=37); parental verbal abuse and/or witnessing domestic violence (EM group, n= 58); or had no history of maltreatment or Axis I disorders (n=58). The main outcomes measures consisted of the grey matter volume of Lobule I as measured by manual tracing, number and type of alcoholic beverages consumed during a drinking session, number of sessions per month, and monthly drug use, along with family history of drug and alcohol abuse. Lingula thickness was not attenuated by alcohol use or maltreatment history. However, increased lingula thickness was associated with greater consumption of drugs and hard liquor, particularly in physically maltreated subjects who consumed 2.5- and 2.7-fold more alcohol, and used drugs 6.1- and 7.8-fold more frequently than controls or EM subjects, respectively. In conclusion, physical maltreatment was observed to interact with cerebellar morphology resulting in a strong association with alcohol and substance use. Lingula thickness may represent a novel, experientially-sensitive, phenotypic risk factor for enhanced alcohol and drug use, that perhaps modulates sensitivity to these agents.

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Section: Discussionmentioning

confidence: 99%

Cerebellar Lingula Size and Experiential Risk Factors Associated with High Levels of Alcohol and Drug Use in Young Adults

Anderson¹,

Rabi²,

Lukas³

et al. 2009

Cerebellum

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“…There is evidence for EtOH effects on CSF (Nixon, 2008) and vasculature (Altura and Altura, 1984), but we propose compensatory (ie, for shifts of fluid between various brain compartments within a closed space) ventriculomegaly is due to changes in brain tissue properties. Specifically, we posit that EtOH causes widespread intracellular water extravasation leading to shrinkage of brain cells and their process.…”

Section: Discussionmentioning

confidence: 99%

A Mechanism of Rapidly Reversible Cerebral Ventricular Enlargement Independent of Tissue Atrophy

Zahr

Mayer

Rohlfing

et al. 2013

Neuropsychopharmacol

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Ventricular enlargement, a common in vivo marker of aging, disease, and insult, is presumed to reflect atrophy of surrounding brain regions. Pathological mechanisms underlying ventricular enlargement, however, are likely specific to the condition under investigation. Here, multimodal imaging, incorporating structural magnetic resonance imaging (MRI), MR spectroscopy (MRS), and diffusion weighted imaging (DWI), was used in rats exposed to binge ethanol (EtOH) to provide insight into a mechanism of reversible ventricular enlargement. During intoxication, MRI revealed expansion of ventricles, but volume changes in dorsal or ventral hippocampi, caudateputamen, or thalamus were not detectible. MRS of whole-brain parenchyma showed decreases in N-acetylasparate (NAA) and tissue water T2, and increases in choline-containing compounds (Cho). DWI showed decreased diffusivity selective to the thalamus. All MR parameters returned to baseline with 7 days of recovery. Rapid recovery of ventricular volume and the absence of detectable tissue volume reductions in brain regions adjacent to ventricles argue against atrophy as a mechanism of ventricular expansion. Decreased tissue water T2 and decreased thalamic diffusivity suggest lower tissue water content and a role for both NAA and Cho, as osmolytes is proposed. Together, these data support a model of fluid redistribution during acute EtOH intoxication and recovery to account for rapid ventricular volume changes.

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“…Functional uptake assays indicate a generalized tendency for the removal of glutamate from the CSF (Kim et al, 1996; Nixon, 2008). These data indicate the presence of transporters on the apical surface of the choroid plexus.…”

Section: Introductionmentioning

confidence: 99%

Localisation of novel forms of glutamate transporters and the cystine-glutamate antiporter in the choroid plexus: Implications for CSF glutamate homeostasis

Lee

Anderson

Rayfield

et al. 2012

Journal of Chemical Neuroanatomy

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The choroid plexus is a structure within each ventricle of the brain that is composed of fenestrated vessels surrounded by secretory epithelial cells. The epithelial cells are linked by tight junctions to create a permeability barrier. The epithelial cells are derived from neuroectoderm, and are thus defined by some authors as a subtype of macroglia. Glutamate is a tightly regulated substance in the CSF, as it is in the rest of the brain. In the brain macroglia express multiple sodium dependent and independent glutamate transporters and are the main regulators of extracellular glutamate. However, the identities of the transporters in the choroid plexus and their localisations have remained poorly defined. In this study we examined the expression and distribution of multiple splice variants of classical sodium-dependent glutamate transporters, as well as the cystine-glutamate antiporter, and the PDZ protein NHERF1, (which acts as a molecular anchor for proteins such as the glutamate transporter GLAST). We identified three forms of sodium-dependent transporters (GLAST1a, GLAST1c and GLT1b) that are expressed at the apical surface of the epithelial cells, a location that matches the distribution of NHERF1 and the cystine-glutamate antiporter. We propose that this coincident localisation of GLAST1a/GLAST1c/GLT1b and the cystine-glutamate antiporter would permit the cyclical trafficking of glutamate and thus optimise the accumulation of cystine for the formation of glutathione in the choroid plexus.

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

Abstract: Impairment of the CP by ethanol intoxication and by thiamin-deficient carbohydrate metabolism has a common, rational explanation that can guide future research.

Cited by 13 publications

References 111 publications

Cerebellar Lingula Size and Experiential Risk Factors Associated with High Levels of Alcohol and Drug Use in Young Adults

Cerebellar Lingula Size and Experiential Risk Factors Associated with High Levels of Alcohol and Drug Use in Young Adults

A Mechanism of Rapidly Reversible Cerebral Ventricular Enlargement Independent of Tissue Atrophy

Localisation of novel forms of glutamate transporters and the cystine-glutamate antiporter in the choroid plexus: Implications for CSF glutamate homeostasis

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