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Labeling of neuronal receptors and transporters with quantum dots.
Chang JC, Kovtun O, Blakely RD, Rosenthal SJ
(2012) Wiley Interdiscip Rev Nanomed Nanobiotechnol 4: 605-19
MeSH Terms: Animals, Fluorescent Dyes, Humans, Molecular Imaging, Molecular Probes, Neurons, Neurotransmitter Transport Proteins, Protein Transport, Quantum Dots, Receptors, Neurotransmitter
Show Abstract · Added July 10, 2013
The ability to efficiently visualize protein targets in cells is a fundamental goal in biological research. Recently, quantum dots (QDots) have emerged as a powerful class of fluorescent probes for labeling membrane proteins in living cells because of breakthrough advances in QDot surface chemistry and biofunctionalization strategies. This review discusses the increasing use of QDots for fluorescence imaging of neuronal receptors and transporters. The readers are briefly introduced to QDot structure, photophysical properties, and common synthetic routes toward the generation of water-soluble QDots. The following section highlights several reports of QDot application that seek to unravel molecular aspects of neuronal receptor and transporter regulation and trafficking. This article is closed with a prospectus of the future of derivatized QDots in neurobiological and pharmacological research.
Copyright © 2012 Wiley Periodicals, Inc.
0 Communities
3 Members
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10 MeSH Terms
Editing of neurotransmitter receptor and ion channel RNAs in the nervous system.
Hood JL, Emeson RB
(2012) Curr Top Microbiol Immunol 353: 61-90
MeSH Terms: Adenosine Deaminase, Amino Acid Sequence, Ion Channels, Molecular Sequence Data, Nervous System, RNA Editing, RNA-Binding Proteins, Receptor, Serotonin, 5-HT2C, Receptors, AMPA, Receptors, GABA-A, Receptors, Kainic Acid, Receptors, Neurotransmitter
Show Abstract · Added May 28, 2014
The central dogma of molecular biology defines the major route for the transfer of genetic information from genomic DNA to messenger RNA to three-dimensional proteins that affect structure and function. Like alternative splicing, the post-transcriptional conversion of adenosine to inosine (A-to-I) by RNA editing can dramatically expand the diversity of the transcriptome to generate multiple, functionally distinct protein isoforms from a single genomic locus. While RNA editing has been identified in virtually all tissues, such post-transcriptional modifications have been best characterized in RNAs encoding both ligand- and voltage-gated ion channels and neurotransmitter receptors. These RNA processing events have been shown to play an important role in the function of the encoded protein products and, in several cases, have been shown to be critical for the normal development and function of the nervous system.
0 Communities
1 Members
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12 MeSH Terms
Sigma receptors: potential targets for a new class of antidepressant drug.
Fishback JA, Robson MJ, Xu YT, Matsumoto RR
(2010) Pharmacol Ther 127: 271-82
MeSH Terms: Animals, Antidepressive Agents, Depression, Drug Design, Humans, Receptors, Neurotransmitter, Receptors, sigma, Signal Transduction
Show Abstract · Added July 10, 2013
Despite the widespread and devastating impact of depression on society, our current understanding of its pathogenesis is limited. Likewise, existing treatments are inadequate, providing relief to only a subset of people suffering from depression. The search for more effective antidepressant drugs includes the investigation of new molecular targets. Among them, current data suggests that sigma receptors are involved in multiple processes effecting antidepressant-like actions in vivo and in vitro. This review summarizes accumulated evidence supporting a role for sigma receptors in antidepressant effects and provides a conceptual framework for delineating their potential roles over the course of antidepressant treatment.
2010 Elsevier Inc. All rights reserved.
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1 Members
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8 MeSH Terms
Microarray analysis reveals distinctive signaling between the bed nucleus of the stria terminalis, nucleus accumbens, and dorsal striatum.
Olsen CM, Huang Y, Goodwin S, Ciobanu DC, Lu L, Sutter TR, Winder DG
(2008) Physiol Genomics 32: 283-98
MeSH Terms: Animals, Corpus Striatum, Databases, Factual, Gene Expression Profiling, Gene Regulatory Networks, Genes, Reporter, Green Fluorescent Proteins, Male, Mice, Mice, Inbred C57BL, Nerve Tissue Proteins, Neural Pathways, Neuronal Plasticity, Neurotransmitter Agents, Neurotransmitter Transport Proteins, Nucleus Accumbens, Oligonucleotide Array Sequence Analysis, Receptors, Neurotransmitter, Septal Nuclei, Signal Transduction, Synaptic Transmission, Transcription, Genetic
Show Abstract · Added May 19, 2014
To identify distinct transcriptional patterns between the major subcortical dopamine targets commonly studied in addiction we studied differences in gene expression between the bed nucleus of the stria terminalis (BNST), nucleus accumbens (NAc), and dorsal striatum (dStr) using microarray analysis. We first tested for differences in expression of genes encoding transcripts for common neurotransmitter systems as well as calcium binding proteins routinely used in neuroanatomical delineation of brain regions. This a priori method revealed differential expression of corticotropin releasing hormone (Crh), the GABA transporter (Slc6a1), and prodynorphin (Pdyn) mRNAs as well as several others. Using a gene ontology tool, functional scoring analysis, and Ingenuity Pathway Analysis, we further identified several physiological pathways that were distinct among these brain regions. These two different analyses both identified calcium signaling, G-coupled protein receptor signaling, and adenylate cyclase-related signaling as significantly different among the BNST, NAc, and dStr. These types of signaling pathways play important roles in, amongst other things, synaptic plasticity. Investigation of differential gene expression revealed several instances that may provide insight into reported differences in synaptic plasticity between these brain regions. The results support other studies suggesting that crucial pathways involved in neurotransmission are distinct among the BNST, NAc, and dStr and provide insight into the potential use of pharmacological agents that may target region-specific signaling pathways. Furthermore, these studies provide a framework for future mouse-mouse comparisons of transcriptional profiles after behavioral/pharmacological manipulation.
0 Communities
1 Members
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22 MeSH Terms
Expression of Frizzled genes in developing and postnatal hair follicles.
Reddy ST, Andl T, Lu MM, Morrisey EE, Millar SE
(2004) J Invest Dermatol 123: 275-82
MeSH Terms: Age Factors, Animals, Cell Division, Cytoskeletal Proteins, Female, Frizzled Receptors, Gene Expression Regulation, Developmental, Hair Follicle, Mice, Mice, Inbred BALB C, Pregnancy, Proteins, Proto-Oncogene Proteins, Receptors, Cell Surface, Receptors, G-Protein-Coupled, Receptors, Neurotransmitter, Trans-Activators, Wnt Proteins, beta Catenin
Show Abstract · Added January 30, 2013
Embryonic hair follicle development and postnatal hair growth rely on intercellular communication within the epithelium and between epithelial and mesenchymal cells. Several members of the WNT family of paracrine intercellular signaling molecules are expressed in specific subsets of cells in developing and mature mouse hair follicles, suggesting them as candidates for some of the intercellular signals that operate in these organs. As WNT ligands activate several different signaling pathways, they may play multiple and complex roles in developing and postnatal skin. To begin to investigate these functions, we have used in situ hybridization to identify cells that express Frizzled (Fz) WNT receptor genes, and so are potentially receptive to WNT ligands. We find that several Fz genes are specifically expressed at sites of known activity of the WNT/beta-catenin signaling pathway, allowing us to identify candidate receptors for canonical WNT ligands important in appendage development. The expression of additional Fz genes is specifically elevated at locations and developmental stages other than those that display WNT/beta-catenin pathway activity, suggesting that signaling through alternate WNT pathways may contribute to the development and function of skin and hair.
0 Communities
1 Members
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19 MeSH Terms
Acute amygdalar activation induces an upregulation of multiple monoamine G protein coupled pathways in rat hippocampus.
Benes FM, Burke RE, Walsh J, Berretta S, Matzilevich D, Minns M, Konradi C
(2004) Mol Psychiatry 9: 932-45, 895
MeSH Terms: Amygdala, Animals, Biogenic Monoamines, Disease Models, Animal, Fluorescence Resonance Energy Transfer, GTP-Binding Proteins, Gene Expression Profiling, Gene Expression Regulation, Hippocampus, Injections, Male, Oligonucleotide Array Sequence Analysis, Picrotoxin, RNA, Messenger, Rats, Rats, Sprague-Dawley, Receptors, G-Protein-Coupled, Receptors, Neurotransmitter, Reverse Transcriptase Polymerase Chain Reaction, Schizophrenia
Show Abstract · Added May 27, 2014
A "partial" rodent model for schizophrenia has been used to characterize the regulation of hippocampal genes in response to amygdalar activation. At 96 h after the administration of picrotoxin into the basolateral nucleus, we have observed an increase in the expression of genes associated with 18 different monoamine (ie adrenergic alpha 1, alpha 2 and beta 2, serotonergic 5HT5b and 5HT6, dopamine D4 and muscarinic m1, m2 and m3) and peptide (CCK A and B, angiotensin 1A, mu and kappa opiate, FSH, TSH, LH, GNRH, and neuropeptide Y) G-protein coupled receptors (GPCRs). These latter receptors are associated with three different G protein signaling pathways (Gq, Gs, and Gi) in which significant changes in gene expression were also noted for adenylate cyclase (AC4), phosphodiesterase (PDE4D), protein kinase A (PKA), and protein kinase C (PKC). Quantitative RT-PCR was used to validate the results and demonstrated that there were predictable increases of three GPCRs selected for this analysis, including the dopamine D4, alpha 1b, and CCK-B receptors. Eight out of the nine monoamine receptors showing these changes have moderate to high affinity for the atypical antipsychotic, clozapine. Taken together, these results suggest that amygdalar activation may play a role in the pathophysiology and treatment of psychosis by regulating the activity of multiple GPCR and metabolic pathways in hippocampal cells.
0 Communities
1 Members
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20 MeSH Terms
Differential effects of typical and atypical antipsychotic drugs on striosome and matrix compartments of the striatum.
Bubser M, Deutch AY
(2002) Eur J Neurosci 15: 713-20
MeSH Terms: Animals, Antipsychotic Agents, Clozapine, Dyskinesia, Drug-Induced, Excitatory Amino Acid Antagonists, Haloperidol, Male, Muscarinic Antagonists, Neostriatum, Neurons, Neuropil, Proto-Oncogene Proteins c-fos, Raclopride, Rats, Rats, Sprague-Dawley, Receptors, Neurotransmitter, Serotonin Antagonists
Show Abstract · Added May 27, 2014
Administration of typical antipsychotic drugs (APDs) is often accompanied by extrapyramidal side-effects (EPS). Treatment with atypical APDs has a lower incidence of motor side-effects and atypical APDs are superior to typical APDs in treating the negative symptoms of schizophrenia. Although typical APDs strongly induce the immediate-early gene c-fos in the striatum while atypical APDs do so only weakly, it is possible that the effects of atypical APDs are more pronounced within certain regions of the striatum. The striatum contains two histochemically defined compartments, the striosome (patch) and the matrix. These compartments have been well characterized anatomically but their functional attributes are unclear. We therefore examined the effects of typical and atypical APDs on Fos expression in the striosome and matrix of the rat. Typical and atypical APDs were distinguished by the pattern of striatal compartmental activation they induced: the striosome : matrix ratio of Fos-li neurons was greater in rats treated with atypical APDs. Pretreating animals with selective antagonists of receptors that atypical APDs target with high affinity did not increase the striosome : matrix Fos ratio of typical APD-treated rats and thus did not mimic the ratio seen in response to atypical APDs. However, pretreatment with the atypical APD clozapine did recapitulate the characteristic compartmental Fos pattern seen in response to typical APDs. These data suggest that some characteristics of atypical APDs, such as the lower EPS liability and greater reduction of negative symptoms, may be linked to the coordinate regulation of the striatal striosome and matrix.
0 Communities
1 Members
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17 MeSH Terms
Anatomic and molecular principles of psychopharmacology. A primer for psychiatrists.
Heckers S, Konradi C
(2000) Child Adolesc Psychiatr Clin N Am 9: 1-22
MeSH Terms: Adolescent, Animals, Brain, Child, Humans, Mental Disorders, Neurons, Neurotransmitter Agents, Psychotropic Drugs, Receptors, Neurotransmitter, Synaptic Transmission
Show Abstract · Added May 27, 2014
Psychopharmacology uses chemicals to modulate human brain function. Three basic principles of neurotransmission may help to understand the current practice of clinical psychopharmacology. First, the anatomic organization of neurotransmitter systems determines their behavioral affiliation. Second, neurotransmitter receptors modulate the electrical properties (via ion channels) or the biochemical properties (via second-messenger systems) of neurons. Third, the intracellular integration of receptor-mediated responses leads to immediate or delayed effects on neuronal function.
0 Communities
1 Members
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11 MeSH Terms
Acidic peptides in brain: do they act at putative glutamatergic synapses?
Coyle JT, Blakely R, Zaczek R, Koller KJ, Abreu M, Ory-Lavollée L, Fisher R, ffrench-Mullen JM, Carpenter DO
(1986) Adv Exp Med Biol 203: 375-84
MeSH Terms: Animals, Aspartic Acid, Biological Transport, Brain, Brain Chemistry, Brain Mapping, Chlorides, Convulsants, Dipeptides, Glutamates, Hippocampus, Neurotransmitter Agents, Receptors, Glutamate, Receptors, Neurotransmitter, Synaptosomes
Added September 28, 2015
0 Communities
1 Members
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15 MeSH Terms
A re-examination of the interaction of N-acetyl-L-aspartyl-L-glutamate with a subpopulation of rat brain membrane L-[3H]glutamate binding sites.
Blakely RD, Robinson MB, Guarda AS, Coyle JT
(1988) Eur J Pharmacol 151: 419-26
MeSH Terms: Animals, Dipeptides, Kinetics, Male, Membranes, Rats, Receptors, Glutamate, Receptors, Neurotransmitter
Show Abstract · Added July 10, 2013
The neuropeptide, N-acetyl-L-aspartyl-L-glutamate (NAAG) has been reported to act at a subpopulation of putative quisqualate receptors on the basis of its competitive inhibition of specific binding of L-[3H]glutamate and on the basis of quisqualate-sensitive binding of [3H]NAAG radiolabeled on the glutamate moiety. Recently, a membrane-bound metallopeptidase, N-acetylated alpha-linked acidic dipeptidase (NAALADase), which cleaves NAAG to N-acetyl-aspartate (NAA) and glutamate, has been characterized and has been shown to exhibit optimal activity under incubation conditions used to measure NAAG binding sites. Accordingly, we have examined whether NAALADase mediated release of glutamate from NAAG might account for the receptor binding results. Insertion of empirically derived kinetic constants for NAALADase hydrolysis of NAAG into a theoretical model for peptide-derived glutamate inhibition of [3H]glutamate binding reveals that NAAG can appear to displace, with high affinity, a subpopulation of [3H]glutamate labeled sites, and yet have little or no intrinsic activity for these sites. Furthermore, empirical data relating time and protein concentration to NAAG displacement of [3H]glutamate binding are more consistent with a proteolytic mechanism rather than an equilibrium interaction of the peptide with membrane receptors. Coupled with recent findings attributing the Cl- -dependent glutamate binding to a sequestration phenomenon, these results demonstrate that the inferred action of NAAG at glutamate synaptic receptors through previous radioligand binding studies is probably incorrect. Furthermore, these studies offer a general caution regarding the conclusions about subpopulations of receptors drawn from receptor binding assays conducted with ligands, which may be structurally modified by enzymatic processes.
1 Communities
1 Members
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8 MeSH Terms