The messenger RNAs for the N-methyl- d-aspartate receptor subunits show region-specific expression of different subunit composition in the human brain

Rigby, Michael; Bourdellès, B. Le; Heavens, R.P.; Kelly, Steven L.; Smith, David W.; Butler, Amy K.; Hammans, R.; Hills, R. E.; Xuereb, John H.; Hill, Ray; Whiting, Paul J.; Sirinathsinghji, D.J.S.

doi:10.1016/0306-4522(96)00089-9

Cited by 87 publications

(63 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The overall patterns of NR1 expression in the hippocampal and cortical regions of control animals are in close agreement with those of previous studies (Rigby et al, 1996;Rudolf et al, 1996). The marked alteration in cytoarchitectural boundaries within the pyramidal cell layer of CA1 and within the cortex is also compatible with the significant reductions in maze performance exhibited by EHYP-treated rats (Morris, 1989).…”

Section: Nmda-c-fos Immunoreactivitysupporting

confidence: 90%

Behavioral and Anatomical Correlates of Chronic Episodic Hypoxia during Sleep in the Rat

2001

View full text Add to dashboard Cite

The role played by chronic episodic hypoxia (EHYP) in the neurocognitive morbidity of obstructive sleep apnea (OSA) is unknown. Sleep recordings, Morris water maze experiments, and immunohistochemistry for NMDA NR1 glutamate receptor, c-fos protein, and apoptosis [nuclear immunoreactivity for single-stranded DNA and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling assay] were conducted in EHYP-exposed Sprague Dawley male rats. Exposures consisted of up to14 d in an environmental chamber in which O 2 concentrations were cycled between 10 and 21% every 90 sec or 30 min during 12 hr of daylight. For the remaining 12 hr, EHYP rats breathed room air, while controls spent 14 d in room air. Although EHYP induced significant disruption of sleep architecture during the initial day of exposure, sleep patterns normalized thereafter. Marked increases in apoptosis occurred in the CA1 hippocampal region (sevenfold) and cortex (Cx; eightfold) after 1-2 d of EHYP but not in CA3 and were followed by decreases toward normoxic levels by 14 d. Double labeling for NMDA NR1 and c-fos revealed marked architectural disorganization in CA1 and Cx with increases in c-fos over time. Rats exposed to EHYP displayed significantly longer escape latencies and swim path lengths to escape a hidden platform during 12 training trials given over 2 d. Differences in the performances of EHYP and control rats, although reduced, persisted after 14 d of recovery. We conclude that EHYP is associated with marked cellular changes over time within neural regions associated with cognitive functions. Furthermore, EHYP impaired performance during acquisition of a cognitive spatial task without affecting sensorimotor function. Such changes may underlie components of the learning and memory impairments found in OSA.

show abstract

Section: Nmda-c-fos Immunoreactivitysupporting

confidence: 90%

Behavioral and Anatomical Correlates of Chronic Episodic Hypoxia during Sleep in the Rat

2001

View full text Add to dashboard Cite

show abstract

“…These findings are consistent with in situ hybridization studies showing expression of the mRNA encoding NR1 subunit in human brain stem nuclei. Of the NR2 family, only NR2C was found to be expressed in these nuclei, including the LC (Rigby et al, 1996). Additionally, Allgaier et al (2001) demonstrated expression of NR2C mRNA by the majority of rat LC cells examined by single-cell RT-PCR analysis.…”

Section: Nmdar Subunit Composition In the Human Lcmentioning

confidence: 92%

Elevated Levels of the NR2C Subunit of the NMDA Receptor in the Locus Coeruleus in Depression

Karolewicz

Stockmeier

Ordway

2005

Neuropsychopharmacol

View full text Add to dashboard Cite

Low levels of the intracellular mediator of glutamate receptor activation, neuronal nitric oxide synthase (nNOS) were previously observed in locus coeruleus (LC) from subjects diagnosed with major depression. This finding implicates abnormalities in glutamate signaling in depression. Receptors responding to glutamate in the LC include ionotropic N-methyl-D-aspartate receptors (NMDARs). The functional NMDAR is a hetero-oligomeric structure composed of NR1 and NR2 (A-D) subunits. Tissue containing the LC and a nonlimbic LC projection area (cerebellum) was obtained from 13 and 9 matched pairs, respectively, of depressed subjects and control subjects lacking major psychiatric diagnoses. NMDAR subunit composition in the LC was evaluated in a psychiatrically normal subject. NR1 and NR2C subunit immunoreactivities in LC homogenates showed prominent bands at 120 and 135 kDa, respectively. In contrast to NR1 and NR2C, very weak immunoreactivity of NR2A and NR2B subunits was observed in the LC. Possible changes in concentrations of NR1 and NR2C that might occur in depression were assessed in the LC and cerebellum. The overall amount of NR1 immunoreactivity was normal in the LC and cerebellum in depressed subjects. Amounts of NR2C protein were significantly higher ( þ 61%, p ¼ 0.003) in the LC and modestly, but not significantly, elevated in the cerebellum ( þ 35%) of depressives as compared to matched controls. Higher levels of NR2C subunit implicate altered glutamatergic input to the LC in depressive disorders.

show abstract

“…The NR 1 subunit is often considered obligatory for functional NMDA receptor assemblies, but the remaining subunits can vary. Additional heterogeneity is conferred by eight alternative splice variants of the NR 1 subunit that have different expression patterns within the human brain (55). The pattern of subunits assembled to form specific glutamate receptors varies from brain region to brain region (55).…”

mentioning

confidence: 99%

“…Additional heterogeneity is conferred by eight alternative splice variants of the NR 1 subunit that have different expression patterns within the human brain (55). The pattern of subunits assembled to form specific glutamate receptors varies from brain region to brain region (55). In the cerebral cortex and the hippocampus, NMDA receptors are assembled from NR 1 , NR 2A , and NR 2B subunits, and the NR 2C and NR 2D subunits are generally thought not to be expressed at appreciable levels (54, 56) (but see reference 38).…”

mentioning

confidence: 99%

N-Methyl-d-Aspartic Acid Receptor Expression in the Dorsolateral Prefrontal Cortex of Elderly Patients With Schizophrenia

Dracheva

Marras²,

Elhakem³

et al. 2001

AJP

181

103

View full text Add to dashboard Cite

Objective:The N-methyl-D-aspartic acid (NMDA) class of glutamate receptors has received attention in the pathophysiology of schizophrenia because of the similarity between some schizophrenic symptoms and symptoms caused by NMDA antagonists. To determine if NMDA receptor abnormalities were present at the mRNA level, expression of NMDA receptor (NR) subunits NR 1 , NR 2A , and NR 2B was measured in specimens from the dorsolateral prefrontal cortex and the occipital cortex of elderly patients with schizophrenia and normal elderly subjects.Method: Postmortem specimens from antemortem assessed and diagnosed elderly patients with schizophrenia (N=26) were compared with those from a neuropathologically and neuropsychiatrically normal elderly comparison group (N=13) and from patients with Alzheimer's disease (N=10). The mRNA expression of the NR 1 , NR 2A , and NR 2B subunits and of postsynaptic density 95 (PSD-95), a protein associated with postsynaptic NMDA receptors, was studied with quantitative real-time reverse transcriptase polymerase chain reaction.Results: Expression of NR 1 and NR 2A but not NR 2B subunits was higher in the dorsolateral prefrontal cortex and the occipital cortex of patients with schizophrenia than in the normal and Alzheimer's disease groups. In contrast, NR 1 expression was significantly lower in the Alzheimer's disease group. Occipital cortex expression of PSD-95 was higher in the schizophrenic subjects and correlated strongly with the expression of NR 2A and NR 2B in both cortical regions and with expression of NR 1 in the occipital cortex. These results were not influenced by neuroleptic exposure history, postmortem interval, or age of the subject.Conclusions: NMDA receptor subunits are abnormally expressed in elderly patients with schizophrenia. The disproportionate expression of the NR 1 and NR 2A subunits relative to NR 2B expression may have implications for the pathophysiology of schizophrenia and the sensitivity of schizophrenic patients to glutamate and glutamatergic drugs. Several neurochemical hypotheses have been proposed to explain the origin of schizophrenia, including abnormal dopamine, serotonin (5-HT), γ-aminobutyric acid (GABA), and/or glutamate neurotransmission in different regions of the brain (1-8). Abnormalities in the dorsolateral prefrontal cortex have figured prominently in many of these hypotheses, in part due to results of in vivo imaging and neuroanatomical studies (9-11), although there is evidence for structural, metabolic, and neurochemical abnormalities in many other brain regions, including the thalamus, the hippocampus, and the cingulate and entorhinal cortices (1,(12)(13)(14)(15)(16)(17)(18)(19).Strong evidence supporting an association between glutamatergic hypofunction and schizophrenia has come from pharmacological studies showing that N-methyl-Daspartic acid (NMDA) receptor antagonists such as phencyclidine and ketamine can induce many of the psychotic signs and symptoms of schizophrenia in normal subjects, as well as exacerbate these signs and symptom...

show abstract

The messenger RNAs for the N-methyl- d-aspartate receptor subunits show region-specific expression of different subunit composition in the human brain

Cited by 87 publications

References 102 publications

Behavioral and Anatomical Correlates of Chronic Episodic Hypoxia during Sleep in the Rat

Behavioral and Anatomical Correlates of Chronic Episodic Hypoxia during Sleep in the Rat

Elevated Levels of the NR2C Subunit of the NMDA Receptor in the Locus Coeruleus in Depression

N-Methyl-d-Aspartic Acid Receptor Expression in the Dorsolateral Prefrontal Cortex of Elderly Patients With Schizophrenia

Contact Info

Product

Resources

About