Regional and subunit specific changes in NMDA receptor mRNA and immunoreactivity in mouse brain following chronic ethanol ingestion

Snell, Lawrence D.; Nunley, Karin; Lickteig, Ronald; Browning, Michael; Tabakoff, Boris; Hoffman, Paula L.

doi:10.1016/0169-328x(96)00038-1

Cited by 165 publications

(70 citation statements)

References 32 publications

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“…Immunoprecipitation under these conditions was previously shown to isolate 90 Ϯ 1% of NR2A and 93 Ϯ 1% NR2B subunits as determined by Western blotting of pellets and final supernatants (33). Previous studies also demonstrated that the antibodies to NR2A and NR2B do not cross-react in immunoprecipitation or Western blotting experiments (32,33). Control experiments were conducted in which the fusion protein used to generate the NR2A and NR2B antibodies was absorbed with the respective antibody for 1 h prior to immunoprecipitation.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Tyrosine Dephosphorylation and Ethanol Inhibition of N-Methyl-d-aspartate Receptor Function

Alvestad¹,

Grosshans²,

Coultrap³

et al. 2003

Journal of Biological Chemistry

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NMDA1 receptors are ionotropic glutamate receptors that mediate calcium and sodium entry into neurons. In the CA1 region of the hippocampus, activation of these receptors is known to be required for induction of long term potentiation (LTP), a cellular process proposed by many as a possible mechanism of memory formation. Aberrant NMDA receptor function can result in cell death and may have implications in pathophysiologic disorders such as Parkinson's disease and epilepsy as well as age-related dementias like Alzheimer's disease (7-11). NMDA receptors are heteromeric assemblies of NR1 and NR2 subunits. The NR1 family is composed of a single gene, which can be alternatively spliced to generate eight theoretical splice variants (12). The NR2 family includes four genes, each encoding a unique subunit: NR2A, NR2B, NR2C, and NR2D (13). A third gene family, NR3, has been discovered, but the function of these subunits is not well understood. Whereas the NR1 subunit is required for a functional channel, differential incorporation of NR2 subunits regulates receptor function. The NR2 subunits, particularly NR2A and NR2B, have been shown to influence the sensitivity of NMDA receptors to ethanol block in cultured neurons as wells as transfected HEK293 cells and oocytes (14 -17). More recent studies have indicated that NR1 subunits may also play a key role in mediating the effects of ethanol on channel activity (18 -20).Ethanol is known to have widespread effects on the central nervous system. Ethanol inhibits transmission at the NMDAR subtype of glutamatergic excitatory synapses and enhances inhibitory GABAergic synaptic transmission. In addition, we and others have demonstrated that ethanol blocks LTP in the hippocampus (6,(21)(22)(23). Given that NMDA receptors are both required for induction of LTP and inhibited by ethanol, it is likely that inhibition of LTP by ethanol in the hippocampus is due, at least in part, to inhibition of NMDA receptors. The molecular mechanisms of this inhibition however, remain unknown.One hypothesis that we favor is that ethanol may inhibit the NMDAR by reducing its phosphorylation. Indeed, ethanol has been shown to enhance protein-tyrosine phosphatase activity and also inhibit receptor tyrosine kinase activity (24, 25). Moreover, previous studies suggest that Fyn, a member of the Src family of tyrosine kinases, may be a key player in regulating the sensitivity of NMDARs to ethanol in the hippocampus (26 -28

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Section: Methodsmentioning

confidence: 99%

“…Materials-Rabbit polyclonal antibodies to NR2A and NR2B subunits and to phospho-Tyr-1472 of NR2B have been characterized previously (32)(33)(34). Monoclonal anti-phosphotyrosine clone 4G10 was purchased from Upstate Biotechnology, Inc. (Lake Placid, NY).…”

Section: Methodsmentioning

confidence: 99%

Tyrosine Dephosphorylation and Ethanol Inhibition of N-Methyl-d-aspartate Receptor Function

Alvestad¹,

Grosshans²,

Coultrap³

et al. 2003

Journal of Biological Chemistry

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“…While some investigators have reported increases in NR2B mRNA expression following chronic alcohol exposure in vitro (Hu et al 1996; Snell et al 1996), and in vivo (Follesa and Ticku 1995; Kash et al 2009; Roberto et al 2006) such increases have not been observed in every brain region (Cebere et al 1999; Floyd et al 2003; Läck et al 2005). Increases in NR2B, and to a lesser extent NR2A, protein expression have also been observed using immunologic techniques after both in vitro and in vivo EtOH exposure (Kash et al 2005; Obara et al 2009; Snell et al 1996). However, other investigators did not observe increased expression of this protein.…”

Section: Chronic Ethanol Actionsmentioning

confidence: 97%

Synaptic Effects Induced by Alcohol

Lovinger

Roberto

2010

Current Topics in Behavioral Neurosciences

125

152

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Ethanol (EtOH) has effects on numerous cellular molecular targets, and alterations in synaptic function are prominent among these effects. Acute exposure to EtOH activates or inhibits the function of proteins involved in synaptic transmission, while chronic exposure often produces opposing and/or compensatory/homeostatic effects on the expression, localization, and function of these proteins. Interactions between different neurotransmitters (e.g., neuropeptide effects on release of small molecule transmitters) can also influence both acute and chronic EtOH actions. Studies in intact animals indicate that the proteins affected by EtOH also play roles in the neural actions of the drug, including acute intoxication, tolerance, dependence, and the seeking and drinking of EtOH. This chapter reviews the literature describing these acute and chronic synaptic effects of EtOH and their relevance for synaptic transmission, plasticity, and behavior.

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“…One of the selective effects of alcohol has been determined to be the inhibition of glutamatergic neurotransmission by antagonizing N-methyl-D-aspartate (NMDA) receptors (Grant et al, 1990; Chen et al, 1997). Furthermore, one of the effects of chronic alcohol exposure is the upregulation of NMDA receptors that results from chronic inhibition of glutamate transmission as a compensatory mechanism (Grant et al, 1990; Sanna et al, 1993; Snell et al, 1996; Chen et al, 1997). In addition, the effects of alcohol withdrawal have been found to be associated with increased extracellular glutamate levels in the striatum (Rossetti and Carboni, 1995), and enhanced NMDA sensitivity in the nucleus accumbens (NAc) of alcohol dependent rats (Siggins et al, 2003).…”

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confidence: 99%

Role of glutamate transporter 1 in the attenuation of alcohol intake

Sari

2014

Front. Neurosci.

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Regional and subunit specific changes in NMDA receptor mRNA and immunoreactivity in mouse brain following chronic ethanol ingestion

Cited by 165 publications

References 32 publications

Tyrosine Dephosphorylation and Ethanol Inhibition of N-Methyl-d-aspartate Receptor Function

Tyrosine Dephosphorylation and Ethanol Inhibition of N-Methyl-d-aspartate Receptor Function

Synaptic Effects Induced by Alcohol

Role of glutamate transporter 1 in the attenuation of alcohol intake

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