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Neurotransmitter Receptors (neurotransmitter + receptor)
Selected AbstractsThe M3/M4 cytoplasmic loop of the ,1 subunit restricts GABAARs lateral mobility: A study using fluorescence recovery after photobleaching,CYTOSKELETON, Issue 12 2006Macarena Perán Abstract A crucial problem in neurobiology is how neurons are able to maintain neurotransmitter receptors at specific membrane domains. The large structural heterogeneity of gamma aminobutyric acid receptors (GABAARs) led to the hypothesis that there could be a link between GABAAR gene diversity and the targeting properties of the receptor complex. Previous studies using Fluorescence Recovery After Photobleaching (FRAP) have shown a restricted mobility in GABAARs containing the ,1 subunit. The M3/M4 cytoplasmic loop is the region of the ,1 subunit with the lowest sequence homology to other subunits. Therefore, we asked whether the M3/M4 loop is involved in cytoskeletal anchoring and GABAAR clustering. A series of ,1 chimeric subunits was constructed: ,1CH (control subunit), ,1CD (Cytoplasmic loop deleted), ,1CD2, and ,1CD3 (,1 with the M3/M4 loop from the ,2 and ,3 subunits, respectively). Our results using FRAP indicate an involvement of the M3/M4 cytoplasmic loop of the ,1 subunit in controlling receptor lateral mobility. On the other hand, inmunocytochemical approaches showed that this domain is not involved in subunit targeting to the cell surface, subunit-subunit assembly, or receptor aggregation. Cell Motil. Cytoskeleton 2006. © 2006 Wiley-Liss, Inc. [source] Neuropathology of Rett syndromeDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2002Dawna Duncan Armstrong Abstract Rett Syndrome is unlike any other pediatric neurologic disease, and its clinical-pathologic correlation can not be defined with standard histology techniques. Based on hypotheses suggested by careful clinical observations, the nervous system of the Rett child has been explored utilizing morphometry, golgi preparations, computerized tomography, magnetic resonance imaging, chemistry, immunocytochemistry, autoradiography, and molecular biologic techniques. From these many perspectives we conclude that Rett syndrome is not a typical degenerative disorder, storage disorder, nor the result of gross malformation, infectious or neoplastic processes. There remain regions of the brain that have not been studied in detail but the available data suggest that the neuropathology of Rett syndrome can be summarized as follows: the Rett brain is small for the age and the height of the patient; it does not become progressively smaller over three to four decades; it has small dendritic trees in pyramidal neurons of layers III and V in selected lobes (frontal, motor, and temporal); it has small neurons with an increased neuronal packing density; it has an immature expression of microtubular protein-2 and cyclooxygenase; it exhibits a changing pattern of neurotransmitter receptors with an apparent reduction in many neurotransmitters, possibly contributing to some symptomatology. A mutation in Mecp2 causes this unique disorder of brain development. Neuronal mosaicism for normal and mutated Mecp2 produces a consistent phenotype in the classic female patient and a small brain with some preserved islands of function, but with an inability to support hand use and speech. This paper summarizes our current observations about neuropathology of Rett syndrome. MRDD Research Reviews 2002;8:72,76. © 2002 Wiley-Liss, Inc. [source] Molecular Neuropathology of Temporal Lobe Epilepsy: Complementary Approaches in Animal Models and Human Disease TissueEPILEPSIA, Issue 2007Michael Majores Summary:, Patients with temporal lobe epilepsies (TLE) frequently develop pharmacoresistance to antiepileptic treatment. In individuals with drug-refractory TLE, neurosurgical removal of the epileptogenic focus provides a therapy option with high potential for seizure control. Biopsy specimens from TLE patients constitute unique tissue resources to gain insights in neuropathological and molecular alterations involved in human TLE. Compared to human tissue specimens in most neurological diseases, where only autopsy material is available, the bioptic tissue samples from pharmacoresistant TLE patients open rather exceptional preconditions for molecular biological, electrophysiological as well as biochemical experimental approaches in human brain tissue, which cannot be carried out in postmortem material. Pathological changes in human TLE tissue are multiple and relate to structural and cellular reorganization of the hippocampal formation, selective neurodegeneration, and acquired changes of expression and distribution of neurotransmitter receptors and ion channels, underlying modified neuronal excitability. Nevertheless, human TLE tissue specimens have some limitations. For obvious reasons, human TLE tissue samples are only available from advanced, drug-resistant stages of the disease. However, in many patients, a transient episode of status epilepticus (SE) or febrile seizures in childhood can induce multiple structural and functional alterations that after a latency period result in a chronic epileptic condition. This latency period, also referred to as epileptogenesis, cannot be studied in human TLE specimens. TLE animal models may be particularly helpful in order to shed characterize new molecular pathomechanisms related to epileptogenesis and open novel therapeutic strategies for TLE. Here, we will discuss experimental approaches to unravel molecular,neuropathological aspects of TLE and highlight characteristics and potential of molecular studies in human and/or experimental TLE. [source] Distribution of glycine receptor subunits on primate retinal ganglion cells: a quantitative analysisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2000Bin Lin Abstract This study investigates the distribution of inhibitory neurotransmitter receptors on sensory neurons. Ganglion cells in the retina of a New World monkey, the common marmoset Callithrix jacchus, were injected with Lucifer yellow and Neurobiotin and subsequently processed with antibodies against one (,1), or against all subunits, of the glycine receptor, or against the anchoring protein gephyrin. Immunoreactive (IR) puncta representing glycine receptor or gephyrin clusters were found on the proximal and the distal dendrites of all ganglion cell types investigated. For both parasol and midget cells, the density of receptor clusters was greater on distal than proximal dendrites for all antibodies tested. In parasol cells the average density for the ,1 subunit of the glycine receptor was 0.087 IR puncta/µm of dendrite, and for all subunits it was 0.119 IR puncta/µm of dendrite. Thus, the majority of glycine receptors on parasol cells contain the ,1 subunit. For parasol cells, we estimated an average of 1.5 glycinergic synapses/100 µm2 dendritic membrane on proximal dendrites and about 9.4 glycinergic synapses/100 µm2 on distal dendrites. The segregation of receptors to the distal dendrites appears to be a common feature of inhibitory neurotransmitter input to parasol and midget cells, and might be associated with the receptive field surround mechanism. [source] Calcium signaling in invertebrate glial cellsGLIA, Issue 7 2006Christian Lohr Abstract Calcium signaling studies in invertebrate glial cells have been performed mainly in the nervous systems of the medicinal leech (Hirudo medicinalis) and the sphinx moth Manduca sexta. The main advantages of studing glial cells in invertebrate nervous systems are the large size of invertebrate glial cells and their easy accessibility for optical and electrophysiological recordings. Glial cells in both insects and annelids express voltage-gated calcium channels and, in the case of leech glial cells, calcium-permeable neurotransmitter receptors, which allow calcium influx as one major source for cytosolic calcium transients. Calcium release from intracellular stores can be induced by metabotropic receptor activation in leech glial cells, but appears to play a minor role in calcium signaling. In glial cells of the antennal lobe of Manduca, voltage-gated calcium signaling changes during postembryonic development and is essential for the migration of the glial cells, a key step in axon guidance and in stabilization of the glomerular structures that are characteristic of primary olfactory centers. © 2006 Wiley-Liss, Inc. [source] VSD: A database for schizophrenia candidate genes focusing on variations,HUMAN MUTATION, Issue 1 2004Min Zhou Abstract Schizophrenia is a common mental disease characterized by delusions, hallucinations, and formal thought disorder. It has been demonstrated with genetic evidence that the disease is a polygenic disorder. Pharmacological, neurochemical, and clinical studies have suggested a number of schizophrenia susceptibility loci. In order to systematically search for genes with small effect in the development of schizophrenia, a database called VSD was established to provide variation data for publicly available candidate genes. Most of the genes encode neurotransmitter receptors, neurotransmitter transporters, and the enzymes involved in their metabolism. Other candidate genes extracted from published literature are also included. The variation information has been collected from publicly available mutation and polymorphism databases such as dbSNP, HGVbase, and OMIM, with single nucleotide polymorphism (SNP) being the most abundant form of collected variations. Reference sequences from NCBI's RefSeq database are used as references when positioning variation at transcript and protein levels. The nonsynonymous SNPs (nsSNPs) that lead to amino acid changes in the functional sites or domains of proteins are distinguished since they are more likely to affect protein function and would be target SNPs for association studies. In addition to variation data, gene descriptions, enzyme information, and other biological information for each gene locus are also included. The latest version of VSD contains 23,648 variations assigned to a total of 186 genes. Five-hundred eighty-eight domains and sites annotated in the SWISS-PROT and InterPro databases are found to contain nsSNPs. VSD may be accessed via the World Wide Web (www.chgb.org.cn/vsd.htm) and will be developed as an up-to-date and comprehensive locus-specific resource for identifying susceptibility genes for schizophrenia. Hum Mutat 23:1,7, 2004. © 2003 Wiley-Liss, Inc. [source] Selectivity of lynx proteins on insect nicotinic acetylcholine receptors in the brown planthopper, Nilaparvata lugensINSECT MOLECULAR BIOLOGY, Issue 3 2010B. Yang Abstract Neuronal nicotinic acetylcholine receptors (nAChRs) are major excitatory neurotransmitter receptors in both vertebrates and invertebrates. Two lynx proteins (Nl-lynx1 and Nl-lynx2) have been identified in the brown planthopper, Nilaparvata lugens, which act as modulators on insect nAChRs. In the present study, two lynx proteins were found to act on the triplet receptor Nl,1/Nl,2/,2 expressed in Xenopus oocytes, increasing agonist-evoked macroscopic currents, but not changing agonist sensitivity and desensitization properties. Nl-lynx1 and Nl-lynx2 increased Imax (maximum responses) of acetylcholine to 4.85-fold and 2.40-fold of that of Nl,1/Nl,2/,2 alone, and they also increased Imax of imidacloprid to 2.57-fold and 1.25-fold. Although, on another triplet nAChRs Nl,3/Nl,8/,2, Nl-lynx2 increased Imax of acetylcholine and imidacloprid to 3.63-fold and 2.16-fold, Nl-lynx1 had no effects on Imax of either acetylcholine or imidacloprid. The results demonstrate the selectivity of lynx proteins for different insect nAChR subtypes. This selectivity was also identified in native N. Lugens. Co-immunoprecipitation was found between Nl,1/Nl,2-containing receptors and both Nl-lynx1 and Nl-lynx2, but was only found between Nl,3/Nl,8-containing receptors and Nl-lynx2. When the previously identified Nl,1Y151S and Nl,3Y151S mutations were included (Nl,1Y151S/Nl,2/,2 and Nl,3Y151S/Nl,8/,2), the increase in Imax of imidacloprid, but not acetylcholine, caused by co-expression of Nl-lynx1 and Nl-lynx2 was more noticeable than that of their wildtype counterparts. Taken together, these data suggest that two modulators, Nl-lynx1 and Nl-lynx2, might serve as an influencing factor in target site insensitivity in N. lugens, such as Y151S mutation. [source] G-protein coupled receptors: SAR analyses of neurotransmitters and antagonistsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2004C. L. Kuo MS Summary Background:, From the deductive point of view, neurotransmitter receptors can be divided into categories such as cholinergic (muscarinic, nicotinic), adrenergic (, - and , -), dopaminergic, serotoninergic (5-HT1,5-HT5), and histaminergic (H1 and H2). Selective agonists and antagonists of each receptor subtype can have specific useful therapeutic applications. For understanding the molecular mechanisms of action, an inductive method of analysis is useful. Objective:, The aim of the present study is to examine the structure,activity relationships of agents acting on G-protein coupled receptors. Method:, Representative sets of G-PCR agonists and antagonists were identified from the literature and Medline [P.M. Walsh (2003) Physicians' desk reference; M.J. O'Neil (2001) The Merck index]. The molecular weight (MW), calculated logarithm of octanol/water partition coefficient (C log P) and molar refraction (CMR), dipole moment (DM), Elumo (the energy of the lowest unoccupied molecular orbital, a measure of the electron affinity of a molecule and its reactivity as an electrophile), Ehomo (the energy of the highest occupied molecular orbital, related to the ionization potential of a molecule, and its reactivity as a nucleophile), and the total number of hydrogen bonds (Hb) (donors and receptors), were chosen as molecular descriptors for SAR analyses. Results:, The data suggest that not only do neurotransmitters share common structural features but their receptors belong to the same ensemble of G-protein coupled receptor with seven to eight transmembrane domains with their resultant dipoles in an antiparallel configuration. Moreover, the analysis indicates that the receptor exists in a dynamic equilibrium between the closed state and the open state. The energy needed to open the closed state is provided by the hydrolysis of GTP. A composite 3-D parameter frame setting of all the neurotransmitter agonists and antagonists are presented using MW, Hb and , as independent variables. Conclusion:, It appears that all neurotransmitters examined in this study operate by a similar mechanism with the G-protein coupled receptors. [source] Band 4.1 proteins are expressed in the retina and interact with both isoforms of the metabotropic glutamate receptor type 8JOURNAL OF NEUROCHEMISTRY, Issue 6 2008Melanie Rose Abstract The function of the CNS depends on the correct regulation of neurotransmitter receptors by interacting proteins. Here, we screened a retinal cDNA library for proteins interacting with the intracellular C-terminus of the metabotropic glutamate receptor isoform 8a (mGluR8a). The band 4.1B protein binds to the C-termini of mGluR8a and mGluR8b, co-localizes with these glutamate receptors in transfected mammalian cells, facilitates their cell surface expression and inhibits the mGluR8 mediated reduction of intracellular cAMP concentrations. In contrast, no interaction with 4.1B was observed for other mGluRs tested. Amino acids encoded by exons 19 and 20 of 4.1B and a stretch of four basic amino acids present in the mGluR8 C-termini mediate the protein interaction. Besides binding to 4.1B, mGluR8 isoforms interact with 4.1G, 4.1N, and 4.1R. Because band 4.1 transcripts undergo extensive alternative splicing, we analyzed the splicing pattern of interacting regions and detected a 4.1B isoform expressed specifically in the retina. Within this tissue, mGluR8 and 4.1B, 4.1G, 4.1N, and 4.1R show a comparable distribution, being expressed in both synaptic layers and in somata of the ganglion cell layer. In summary, our studies identified band 4.1 proteins as new players for the mGluR8 mediated signal transduction. [source] Protein aggregation in postsynaptic density after transient brain ischemiaJOURNAL OF NEUROCHEMISTRY, Issue 2003M. Ber, sewicz Brief cerebral ischemia causes changes in synaptic transmission and in consequence in neuronal function manifested in delayed cell death of CA1 hippocampal region. Postsynaptic density (PSD) is composed by a network of interacting proteins, including scaffolding proteins, neurotransmitter receptors, cytoskeletal proteins and protein kinases. PSD dynamically modulates signal transduction what influence the cell fate. We investigated the composition of the PSD network and effect of ischemia on its complexity. Two experimental procedures were applied. The interaction between PSD-95 and Src, Fyn, Raf-1, paxilin or NMDA receptor subunits were explored using coimmunoprecipitation method. In addition, the effect of ischemia-reperfusion on the density of PSD were evaluated by measurement of is solubility. We find out the decrease in solubility of the PSD-95, NR2A, NR2B and Raf-1. Of interest, the latter was restricted to surviving regions of hippocampus. Acknowledgement:, Financed by PBZ-KBN-002/CD/P05/2000. [source] GeneChip® analysis after acute spinal cord injury in ratJOURNAL OF NEUROCHEMISTRY, Issue 4 2001Guoqing Song Spinal cord injury (SCI) leads to induction and/or suppression of several genes, the interplay of which governs the neuronal death and subsequent loss of motor function. Using GeneChip®, the present study analyzed changes in the mRNA abundance at 3 and 24 h after SCI in adult rats. SCI was induced at T9 level by the New York University impactor by dropping a 10-g weight from a height of 25 mm. Several transcription factors, immediate early genes, heat-shock proteins, pro-inflammatory genes were up-regulated by 3 h, and persisted at 24 h, after SCI. On the other hand, some neurotransmitter receptors and transporters, ion channels, kinases and structural proteins were down-regulated by 3 h, and persisted at 24 h, after SCI. Several genes that play a role in growth/differentiation, survival and neuroprotection were up-regulated at 24 h after SCI. Using real-time quantitative PCR, the changes observed by GeneChip® were confirmed for seven up-regulated (interleukin-6, heat-shock protein-70, heme oxygenase-1, suppressor of cytokine signaling 2, suppressor of cytokine signaling 3, interferon regulatory factor-1, neuropeptide Y), two down-regulated (vesicular GABA transporter and cholecystokinin precursor) and two unchanged (Cu/Zn-superoxide dismutase and phosphatidyl inositol-3-kinase) genes. The present study shows that inflammation, neurotransmitter dysfunction, increased transcription, ionic imbalance and cytoskeletal damage starts as early as 3 h after SCI. In addition to these effects, 24 h after SCI the repair and regeneration process begins in an attempt to stabilize the injured spinal cord. [source] | |||||||||||||