Distribution of nicotinic acetylcholine receptor subunits α7 and β2 in the human brainstem and hippocampal formation (original) (raw)
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International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 1998
Postnatal changes of nicotinic acetylcholine receptor (nAChR) alpha 2, alpha 3, alpha 4, alpha 7 and beta 2 subunits mRNAs were investigated in rat brain using ribonuclease protection assay. Multiple developmental patterns were observed: (1) transient expression during the first few postnatal weeks; alpha 2 in the hippocampus and brain stem, alpha 3 in the striatum, cerebellum and cortex, alpha 4 in the hippocampus, striatum and cerebellum, alpha 7 in the cerebellum and beta 2 in the striatum. (2) Constant expression across development; alpha 2 and alpha 3 in the thalamus, alpha 4 in the cortex, thalamus and brain stem, alpha 7 in the thalamus and brain stem and beta 2 in all brain regions except striatum. (3) Non-detection across development; alpha 2 in the cortex, striatum and cerebellum. (4) Increase with age; alpha 7 in the cortex and hippocampus. (5) Bell-shaped development; alpha 7 in the striatum. Postnatal changes of nAChR isoforms in different brain regions of rat were inve...
Regional distribution of nicotinic acetylcholine receptor in rat brain
Brain Research, 1977
Several recent studies have identified nicotinic acetylcholine receptor (nAChR) in the mammalian nervous system utilizing radiolabeled a-bungarotoxin, a specific and irreversible nicotinic antagonist 7,s,a4,1v 19,21,2.5-29. Brain nAChR is similar to the nAChR from muscle and electric fish in that it has comparable toxin binding kinetics, solubility, isoelectric point and hydrodynamic properties 14,17,1s,23,~7. nAChR in brain is recovered primarily in the synaptosomal fraction, and it is assumed to be a postsynaptic receptor for the neurotransmitter acetylcholine 26.
Immunohistochemical localization of a neuronal nicotinic acetylcholine receptor in mammalian brain
Proceedings of the National Academy of Sciences, 1987
A monoclonal antibody generated against purified acetylcholine receptor from Torpedo electric organ was used to immunohistochemically localize a neuronal nicotinic acetylcholine receptor. Regions of the rat brain stained with this antibody paralleled those areas of the brain exhibiting [3H]nicotine binding sites and corresponded to areas in which mRNAs encoding for alpha subunits of the neuronal nicotinic acetylcholine receptor are present. Thus, the anteroventral thalamus, cortex, hippocampus, medial habenula, interpeduncular nucleus, and substantia nigra/ventral tegmental area exhibited significant immunoreactivity. Neurons of the medial habenula and substantia nigra were densely stained, and processes were prominently delineated. Furthermore, in the projection areas of the medial habenula (interpeduncular nucleus and median raphe) axons were strongly immunoreactive and were distributed to distinct subdivisions of the target sites. The present data suggest that there are several d...
Higher expression of α7 nicotinic acetylcholine receptors in human fetal compared to adult brain
Developmental Brain Research, 2003
Neuronal nicotinic acetylcholine receptors are thought to be involved in regulation of several processes during neurogenesis of the brain. In this study the expression of the a7 nicotinic acetylcholine receptor subtype was investigated in human fetal (9-11 weeks of gestation), middle-aged (28-51 years) and aged (68-94 years) medulla oblongata, pons, frontal cortex, and cerebellum. The specific 125 binding of the a7 receptor antagonist [ I]a-bungarotoxin was significantly higher in fetal than in both middle-aged and aged medulla 125 oblongata and aged pons. No significant decrease in [ I]a-bungarotoxin binding sites was observed from fetal to adult cortex and cerebellum. The a7 mRNA expression was significantly higher in all fetal brain regions investigated, except for aged cortex, than in corresponding middle-aged and aged tissue. The high expression of a7 nicotinic acetylcholine receptors in fetal compared to adult brain supports the view that these receptors play an important role during brain development.
Developmental Brain Research, 1998
Ž . The regional expression of mRNA for the nicotinic acetylcholine receptor nAChR subunits a 3, a4 and a7 was examined in Ž . postmortem brain tissues from controls and patients with Alzheimer's disease AD by using quantitative RT-PCR. In parallel, the numbers of nAChRs were measured by receptor binding. Relative quantification of the nAChR gene transcripts in control brains showed that expression of a 3 was highest in the parietal cortex, frontal cortex and hippocampus, and lower in the temporal cortex and cerebellum. The highest level of a4 mRNA was found in the temporal cortex and cerebellum, while a7 mRNA was equally distributed in all brain regions except for hippocampus where it was less abundant. In comparison with AD brains, no differences in the expression of a 3 and a4 in the temporal cortex, hippocampus and cerebellum were found. The level of a7 mRNA was significantly higher in the w 3 x w 3 x w 125 x hippocampus of AD brains compared to controls. The binding sites for H epibatidine and H nicotine in the temporal cortex and I w 3 x a-bungarotoxin in hippocampus were significantly decreased in AD patients compared to controls. Saturation analysis of H epibatidine binding revealed two classes of binding sites, with a significant reduction of the higher affinity epibatidine binding sites in the temporal cortex of AD brain. The results show that there is a regional distribution of the expression of the different nAChRs subunits in human brain. The findings that the a 3 and a4 mRNA levels were not changed in AD brains suggest that the loss of higher affinity epibatidine binding sites observed in AD patients cannot be attributed to alternations at the transcriptional level of the a 3 and a4 genes and that causes have to be searched for at the translational andror posttranslational level. The increased mRNA level of a7 previously found in lymphocytes, and now also in the hippocampus of AD patients, indicate that subunit specific changes in gene expression of nAChRs is associated with AD. q
Journal of Neurochemistry, 2001
A synthetic peptide corresponding to the C-terminus of the a3 subunit of the rat neuronal nicotinic acetylcholine receptor (nAChR) was used to generate a rabbit polyclonal a3 antibody. The speci®city of this antibody was characterized by immunoblotting, immunohistochemical and immunoprecipitation techniques. Using this antibody, the relative densities of the a3 subunit were quantitatively determined in different brain regions and in superior cervical ganglion (SCG). Among these regions, SCG, interpeduncular nucleus (IPN) and pineal gland showed the highest levels of a3 protein expression. Habenula and superior colliculi had intermediate levels of expression. Low levels were found in cerebral cortex, hippocampus and cerebellum. The ontogenic pro®le of the a3 subunit in the SCG was also determined. The a3 protein level is low at postnatal day (P 1), but increases rapidly during the ®rst seven postnatal days. This level then plateaus and remains stable through postnatal day 35. These ®ndings suggest that neuronal nAChRs containing the a3 subunit participate in important roles in speci®c regions of the rat brain and the SCG.
Molecular Brain Research, 1998
. Ž . Neuronal nicotinic acetylcholine receptors nAChRs present in the central nervous system CNS , are multimeric proteins constituted of two different subunits, a and b, with different subtype arrangements and different pharmacological and functional properties. By in situ hybridization, we studied the distribution of the mRNA for the a 4 subunit of nAChRs in brains of human 25-week old normal and fragile X fetuses. A strong hybridization signal was detected throughout the thalamus, cortex, pyramidal layer of the Ammon's horn, and the granular layer of the dentate gyrus. Several other areas including the claustrum, caudate nucleus, putamen, globus pallidus, subthalamic nucleus, subiculum, entorhinal cortex, and Purkinje cell layer displayed a low to moderate radiosignal. With few exceptions, our data in the human brain agree those previously reported in the rat. Also, our data indicate that the a 4 subunit mRNA is produced early in the development, in the more differentiated cells, and in a site-specific manner. Additionally, the a 4 mRNA is produced in the brain of fragile X fetuses with the same pattern and same intensity than in the normal fetal brain suggesting that a 4 subunit mRNA production is not altered in the fragile X syndrome. High levels of a 4 subunit mRNA in human fetal brain support the hypothesis of a morphogenic role of nAChRs during the early CNS development. q