Chronic Prenatal Ethanol Exposure Alters Ionotropic Glutamate Receptor Subunit Protein Levels in the Adult Guinea Pig Cerebral Cortex

Dettmer, Todd; Barnes, Alicia; Iqbal, Umar; Bailey, Craig D. C.; Reynolds, James N.; Brien, James F.; Valenzuela, C. Fernando

doi:10.1097/01.alc.0000060521.32215.e9

Cited by 11 publications

(5 citation statements)

References 19 publications

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“…Long-lasting adaptive changes after chronic ethanol exposure during adolescent development in NMDAR subunit expression in different brain regions may contribute to permanent changes within neural circuitry when chronic ethanol exposure is withdrawn. This has been shown in studies investigating chronic prenatal ethanol exposure where long-lasting decreases in NR2B subunit protein expression have been found in the forebrain and hippocampus of the guinea pig and rat (Hughes et al, 1998; Dettmer et al, 2003; Samudio-Ruiz et al, 2010), and reductions in NR2A and [3H] MK-801 binding density in rat (Honse et al, 2003a,b). Such changes may potentially contribute to fetal ethanol syndrome (FAS) and also to deficits observed following adolescent ethanol exposure.…”

Section: Discussionmentioning

confidence: 60%

N-methyl-d-aspartate receptor subunit expression in adult and adolescent brain following chronic ethanol exposure

Pian¹,

Criado²,

Milner³

et al. 2010

Neuroscience

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Substantial evidence suggests that glutamatergic neurotransmission is a critical mediator of the experience-dependent synaptic plasticity that may underlie alcohol dependence. Substance abuse typically begins in adolescence; therefore, the impact of alcohol on glutamatergic systems during this critical time in brain development is of particular importance. The N-methyl-D-aspartate receptor (NMDAR) is involved in developmental mechanisms underlying neuronal differentiation and synaptogenesis and as such may be a target system for alcohol effects during adolescence. In the present study quantitative biochemical determinations were made of the relative abundance of different protein expressions of NMDAR subunits in adolescents and adults after 2 wks of ethanol vapor exposure, and 24 hrs and 2 wks following withdrawal. After 2 wks of ethanol vapor exposure NR1, NR2A, and NR2B subunit expression was found to be increased in hippocampus of the adults. In contrast, 2 wks of ethanol exposure resulted in no significant changes in NR1 and NR2B subunits and a reduction NR2A subunit expression in hippocampus in adolescents. Twenty-four hours and 2 wks following withdrawal from ethanol vapor NR1 and NR2A subunit expression in hippocampus was decreased in adolescents, whereas in adults it had returned to control levels. In frontal cortex, 2 wks of chronic ethanol exposure produced decreases in NR1 subunit expression in both adults and adolescents but also produced decreases in NR2A and NR2B subunit expression in adults that returned or exceeded control levels by 2 wks following withdrawal from ethanol vapor. These results demonstrate that NMDAR subunit composition can be modulated differentially between adolescents and adults by chronic ethanol exposure and withdrawal. These developmental differences in NMDAR subunits composition may also be associated with the enhanced vulnerability of the adolescent brain to ethanol dependence.

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Section: Discussionmentioning

confidence: 60%

N-methyl-d-aspartate receptor subunit expression in adult and adolescent brain following chronic ethanol exposure

Pian¹,

Criado²,

Milner³

et al. 2010

Neuroscience

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“…Characterization of specific NMDAR subunit expression following PAE has, however, yielded more varied results. Several independent laboratories have reported reduced GluN2B expression in whole brain [ 79 , 80 ], cortex [ 81 – 83 ], and hippocampus [ 82 ], as well as reduced PSD-95 associated GluN2B [ 84 ] or synaptosomal GluN2B [ 85 ] in hippocampus following PAE. In contrast, some studies have failed to detect effects of PAE on GluN2B expression in cortex [ 86 – 88 ] or hippocampus [ 89 , 90 ].…”

Section: Discussionmentioning

confidence: 99%

Moderate Prenatal Alcohol Exposure Enhances GluN2B Containing NMDA Receptor Binding and Ifenprodil Sensitivity in Rat Agranular Insular Cortex

et al. 2015

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Prenatal exposure to alcohol affects the expression and function of glutamatergic neurotransmitter receptors in diverse brain regions. The present study was undertaken to fill a current gap in knowledge regarding the regional specificity of ethanol-related alterations in glutamatergic receptors in the frontal cortex. We quantified subregional expression and function of glutamatergic neurotransmitter receptors (AMPARs, NMDARs, GluN2B-containing NMDARs, mGluR1s, and mGluR5s) by radioligand binding in the agranular insular cortex (AID), lateral orbital area (LO), prelimbic cortex (PrL) and primary motor cortex (M1) of adult rats exposed to moderate levels of ethanol during prenatal development. Increased expression of GluN2B-containing NMDARs was observed in AID of ethanol-exposed rats compared to modest reductions in other regions. We subsequently performed slice electrophysiology measurements in a whole-cell patch-clamp preparation to quantify the sensitivity of evoked NMDAR-mediated excitatory postsynaptic currents (EPSCs) in layer II/III pyramidal neurons of AID to the GluN2B negative allosteric modulator ifenprodil. Consistent with increased GluN2B expression, ifenprodil caused a greater reduction in NMDAR-mediated EPSCs from prenatal alcohol-exposed rats than saccharin-exposed control animals. No alterations in AMPAR-mediated EPSCs or the ratio of AMPARs/NMDARs were observed. Together, these data indicate that moderate prenatal alcohol exposure has a significant and lasting impact on GluN2B-containing receptors in AID, which could help to explain ethanol-related alterations in learning and behaviors that depend on this region.

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“…Alternatively, Dettmer and colleagues found a significant decrease in NR2B expression in the cerebral cortex of adult guinea pigs whose mothers had a relatively high maternal blood ethanol concentration of 71 mM (~327 mg/dl) throughout gestation (Dettmer et al, 2003). However, we attribute these apparent discrepancies to differences in blood ethanol concentrations, tissue used and species of animals used in our respective studies.…”

Section: Discussionmentioning

confidence: 99%

Hippocampal N‐Methyl‐d‐Aspartate Receptor Subunit Expression Profiles in a Mouse Model of Prenatal Alcohol Exposure

Samudio-Ruiz

Allan

Sheema

2010

Alcoholism Clin & Exp Res

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Background Although several reports have been published showing prenatal ethanol exposure is associated with alterations in N-methyl-D-aspartate (NMDA) receptor subunit levels and, in a few cases, subcellular distribution, results of these studies are conflicting. Methods We used semi-quantitative immunoblotting techniques to analyze NMDA receptor NR1, NR2A, and NR2B subunit levels in the adult mouse hippocampal formation isolated from offspring of dams who consumed moderate amounts of ethanol throughout pregnancy. We employed subcellular fractionation and immunoprecipitation techniques to isolate synaptosomal membrane- and postsynaptic density protein-95 (PSD-95)-associated pools of receptor subunits. Results We found that, compared to control animals, fetal alcohol-exposed (FAE) adult mice had: (i) increased synaptosomal membrane NR1 levels with no change in association of this subunit with PSD-95 and no difference in total NR1 expression in tissue homogenates; (ii) decreased NR2A subunit levels in hippocampal homogenates, but no alterations in synaptosomal membrane NR2A levels and no change in NR2A-PSD-95 association; and (iii) no change in tissue homogenate or synaptosomal membrane NR2B levels but a reduction in PSD-95-associated NR2B subunits. No alterations were found in mRNA levels of NMDA receptor subunits suggesting that prenatal alcohol-associated differences in subunit protein levels are the result of differences in post-transcriptional regulation of subunit localization. Conclusions Our results demonstrate that prenatal alcohol exposure induces selective changes in NMDA receptor subunit levels in specific subcellular locations in the adult mouse hippocampal formation. Of particular interest is the finding of decreased PSD-95-associated NR2B levels, suggesting that synaptic NR2B-containing NMDA receptor concentrations are reduced in FAE animals. This result is consistent with various biochemical, physiological, and behavioral findings that have been linked with prenatal alcohol exposure.

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Chronic Prenatal Ethanol Exposure Alters Ionotropic Glutamate Receptor Subunit Protein Levels in the Adult Guinea Pig Cerebral Cortex

Abstract: These results demonstrate that chronic prenatal ethanol exposure produces long-lasting effects on the subunit composition of NMDA and AMPA receptors in the cerebral cortex of the adult guinea pig.

Cited by 11 publications

References 19 publications

N-methyl-d-aspartate receptor subunit expression in adult and adolescent brain following chronic ethanol exposure

N-methyl-d-aspartate receptor subunit expression in adult and adolescent brain following chronic ethanol exposure

Moderate Prenatal Alcohol Exposure Enhances GluN2B Containing NMDA Receptor Binding and Ifenprodil Sensitivity in Rat Agranular Insular Cortex

Hippocampal N‐Methyl‐d‐Aspartate Receptor Subunit Expression Profiles in a Mouse Model of Prenatal Alcohol Exposure

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