The messenger RNAs for the N-methyl- d-aspartate receptor subunits show region-specific expression of different subunit composition in the human brain
| Autor: | Paul J. Whiting, Smith David W, Dalip J. S. Sirinathsinghji, Raymond G. Hill, S. Kelly, J.H. Xuereb, A. J. Butler, R. Hills, R. Hammans, B. Le Bourdelles, Michael Rigby, Robert P. Heavens |
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| Rok vydání: | 1996 |
| Předmět: |
Male
medicine.medical_specialty Cerebellum endocrine system diseases Macromolecular Substances Protein subunit Biology Sulfur Radioisotopes Hippocampus Receptors N-Methyl-D-Aspartate Basal Ganglia Internal medicine Gene expression medicine Humans RNA Messenger In Situ Hybridization Aged Aged 80 and over Neurons Temporal cortex Messenger RNA Pyramidal Cells General Neuroscience Subiculum Brain nutritional and metabolic diseases Human brain Middle Aged Entorhinal cortex Temporal Lobe Cell biology medicine.anatomical_structure Endocrinology Organ Specificity Autoradiography Oligonucleotide Probes hormones hormone substitutes and hormone antagonists Brain Stem |
| Zdroj: | Neuroscience. 73:429-447 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/0306-4522(96)00089-9 |
| Popis: | The expression of the messenger RNAs encoding N-methyl- d-aspartate receptor subunits in neurologically normal post-mortem human brain was studied by in situ hybridization. In the caudate, putamen and nucleus accumbens strong hybridization signals were observed for N-methyl- d-aspartate R1−1 messenger RNA but much weaker signals for N-methyl- d-aspartate R1–3 and N-methyl- d-aspartate R1–4. N-Methyl- d-aspartate R1–2 was not detectable. N-methyl- d-aspartate R2B was the only N-methyl- d-aspartate R2 subunit detected in these nuclei. In the hippocampus the messenger RNAs for both N-methyl- d-aspartate R1–1 and N-methyl- d-aspartate R1–4 were strongly expressed in the dentate gyrus, CA3-CA1 pyramidal cells, subiculum, entorhinal cortex and perirhinal cortex. Much lower expression was seen for N-methyl- d-aspartate R1–2 and N-methyl- d-aspartate R1–3. The messenger RNAs for both N-methyl- d-aspartate R2A and N-methyl- d-aspartate R2B, but not N-methyl- d-aspartate R2C, subunits were expressed in the hippocampus. In the temporal cortex all N-methyl- d-aspartate R1 isoforms were expressed (N-methyl- d-aspartate R1–1 and N-methyl- d-aspartate R1–4 being the most abundant) and N-methyl- d-aspartate R2A and N-methyl- d-aspartate R2B but not N-methyl- d-aspartate R2C were also moderately expressed. In the brain stem N-methyl- d-aspartate R1–4 was strongly expressed in various nuclei including the locus coeruleus, nucleus centralis superior and deep pontine nuclei. Only weak expression was seen for N-methyl- d-aspartate R1–1 and N-methyl- d-aspartate R1–3 but not N-methyl- d-aspartate R1–2; of the N-methyl- d-aspartate R2 subunits only N-methyl- d-aspartate R2C was found to be expressed in these nuclei. In the cerebellum all the N-methyl- d-aspartate 1 isoforms were expressed (mostly N-methyl- d-aspartate R1–4) in the Purkinje layer which also expressed N-methyl- d-aspartate R2A and N-methyl- d-aspartate R2C. In the molecular layer cells were found expressing N-methyl- d-aspartate R1–4 and N-methyl- d-aspartate R2B and cells in the granule layer were found to express N-methyl- d-aspartate R1−1, N-methyl- d-aspartate R1–3 and N-methyl- d-aspartate R1–4 and N-methyl- d-aspartate R2C only. Preliminary studies indicated that the messenger RNA for the N-methyl- d-aspartate R2D subunit was not expressed in the above areas of brain. These results give the first demonstration of the distribution of N-methyl- d-aspartate receptor subunit messenger RNAs in the human brain. The region-specific expression of subunit combinations suggests a heterogeneity of N-methyl- d-aspartate receptors with diverse physiological/pathophysiological roles and provides a rationale for the development of discriminatory N-methyl- d-aspartate receptor antagonists to target selective neuronal populations. |
| Databáze: | OpenAIRE |
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