Developmental changes of RNA editing of glutamate receptor subunits GluR5 and GluR6: in vivo versus in vitro

Paschen, Wulf; Schmitt, Justina; Gissel, Cornelia; Dux, E.

doi:10.1016/s0165-3806(96)00193-9

Cited by 47 publications

(27 citation statements)

References 41 publications

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“…53 The extent of GluK2 editing of the Q/R site that we observed in the cerebral tissue of control animals (84%) was consistent with previously reported values of 80%-90% in rodent brains. 51,[55][56][57] The tendency toward slightly greater editing at the Q/R site than at the 2 other sites confirms the previous results of Barbon and colleagues. 51 The editing in the cultured astrocytes was much more extensive than previously reported, [57][58][59] perhaps reflecting the differentiation induced by dBcAMP.…”

Section: Discussionsupporting

confidence: 81%

Fluoxetine affects GluK2 editing, glutamate-evoked Ca²⁺ influx and extracellular signal-regulated kinase phosphorylation in mouse astrocytes

Zhang

et al. 2011

jpn

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. Background:We sought to study the effects of chronic exposure to fluoxetine -a selective serotonin reuptake inhibitor (SSRI) and specific 5-HT 2B receptor agonist in astrocytes -on the expression of kainate receptors (GluK1-5) in cultured astrocytes and in intact brains in mice and on GluK2 editing by adenosine deaminase acting on RNA (ADAR), as well as the ensuing effects of fluoxetine on glutamate-mediated Ca 2+ influx and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in astrocytes. Methods: We performed reverse transcription-polymerase chain reaction (PCR) to assess mRNA expression. We analyzed RNA editing with amplification refractory mutation system PCR and complementary DNA sequencing. Protein expression and ERK phosphorylation were assessed using Western blots. We studied gene silencing with specific small interfering RNAs (siRNA), and we studied intracellular Ca 2+ using fluorometry. Results: All GluK subunits were present in the brain in vivo, and GluK2-5 subunits were present in cultured astrocytes. Fluoxetine upregulated GluK2 and ADAR2. Enhanced GluK2 editing by fluoxetine abolished glutamate-mediated increases in intra cellular Ca 2+ and ERK 1/2 phosphorylation. Enhanced editing of GluK2 was prevented by siRNA against the 5-HT 2B receptor or ADAR2. Limitations: Limitations of our study include the use of an in vitro system, but our cultured cells in many respects behave like in vivo astrocytes. Conclusion: Fluoxetine alters astrocytic glutamatergic function.

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Section: Discussionsupporting

confidence: 81%

Fluoxetine affects GluK2 editing, glutamate-evoked Ca²⁺ influx and extracellular signal-regulated kinase phosphorylation in mouse astrocytes

Zhang

et al. 2011

jpn

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“…Moreover, the editing of GluR5 and GluR6 increases over the course of development (Bernard and Khrestchatisky, 1994). In rodents, unedited subunits predominate in embryonic and early postnatal cells but progressively give way to edited subunits within the first 2 weeks of life to reach the adult ratios of 50 -60% GluR5(Q)/40 -50% GluR5(R) and 15-30% GluR6(Q)/70 -85% GluR6(R) (Sommer et al, 1991;Bernard and Khrestchatisky, 1994;Paschen et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Q/R Site Editing Controls Kainate Receptor Inhibition by Membrane Fatty Acids

Wilding¹,

Zhou²,

Huettner³

2005

J. Neurosci.

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RNA editing within the pore loop controls the pharmacology and permeation properties of ion channels formed by neuronal AMPA and kainate receptor subunits. Genomic sequences for the glutamate receptor 2 (GluR2) subunit of AMPA receptors and the GluR5 and GluR6 subunits of kainate receptors all encode a neutral glutamine (Q) residue within the channel pore that can be converted by RNA editing to a positively charged arginine (R). Receptors comprised of unedited subunits are permeable to calcium and display inwardly rectifying current-voltage relationships, because of blocking of outward current by intracellular polyamines. In contrast, receptors that include edited subunits conduct less calcium, resist polyamine block, and have relatively linear current-voltage relationships. We showed previously that cis-unsaturated fatty acids, including arachidonic acid and docosahexanoic acid, exert a potent block of native kainate receptors as well as homomeric recombinant receptors formed by transfection of heterologous cells with cDNA for the GluR6(R) subunit. Here, we show that fatty acid blockade of recombinant homomeric and heteromeric kainate receptors is strongly dependent on editing at the Q/R site. Recombinant channels that include unedited subunits exhibit significantly weaker block than channels made up of fully edited subunits. Inhibition of fully edited channels is equivalent at voltages from Ϫ70 to ϩ40 mV and is noncompetitive, consistent with allosteric regulation of channel function.

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“…Multiple previous studies have also reported the expression of differential neurotransmitter and receptor properties by neurons, depending on neuronal surroundings (Clendening and Hume, 1990;Paschen et al, 1997), depolarization, specific neurotransmitters (Patterson, 1978), target tissue interactions (Landis, 1990), glial-neuronal communication (Poulter andBrown, 1999), hormones (McCauley andGee, 1995;Zhang et al, 1999), and neurotrophins (Ernsberger and Rohrer, 1988;Iacovitti et al, 1989;Sieber-Blum, 1991).…”

Section: Differentiation Of Transplanted Neuroblasts To a Mature Cpn mentioning

confidence: 98%

Transplanted Neuroblasts Differentiate Appropriately into Projection Neurons with Correct Neurotransmitter and Receptor Phenotype in Neocortex Undergoing Targeted Projection Neuron Degeneration

et al. 2000

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Reconstruction of complex neocortical and other CNS circuitry may be possible via transplantation of appropriate neural precursors, guided by cellular and molecular controls. Although cellular repopulation and complex circuitry repair may make possible new avenues of treatment for degenerative, developmental, or acquired CNS diseases, functional integration may depend critically on specificity of neuronal synaptic integration and appropriate neurotransmitter/receptor phenotype.The current study investigated neurotransmitter and receptor phenotypes of newly incorporated neurons after transplantation in regions of targeted neuronal degeneration of cortical callosal projection neurons (CPNs). Donor neuroblasts were compared to the population of normal endogenous CPNs in their expression of appropriate neurotransmitters (glutamate, aspartate, and GABA) and receptors (kainate-R, AMPA-R, NMDA-R. and GABA-R), and the time course over which this phenotype developed after transplantation.Transplanted immature neuroblasts from embryonic day 17 (E17) primary somatosensory (S1) cortex migrated to cortical layers undergoing degeneration, differentiated to a mature CPN phenotype, and received synaptic input from other neurons. In addition, 23.1 Ϯ 13.6% of the donor-derived neurons extended appropriate long-distance callosal projections to the contralateral S1 cortex. The percentage of donor-derived neurons expressing appropriate neurotransmitters and receptors showed a steady increase with time, reaching numbers equivalent to adult endogenous CPNs by 4-16 weeks after transplantation.These results suggest that previously demonstrated changes in gene expression induced by synchronous apoptotic degeneration of adult CPNs create a cellular and molecular environment that is both permissive and instructive for the specific and appropriate maturation of transplanted neuroblasts. These experiments demonstrate, for the first time, that newly repopulating neurons can undergo directed differentiation with high fidelity of their neurotransmitter and receptor phenotype, toward reconstruction of complex CNS circuitry.

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Developmental changes of RNA editing of glutamate receptor subunits GluR5 and GluR6: in vivo versus in vitro

Cited by 47 publications

References 41 publications

Fluoxetine affects GluK2 editing, glutamate-evoked Ca²⁺ influx and extracellular signal-regulated kinase phosphorylation in mouse astrocytes

Fluoxetine affects GluK2 editing, glutamate-evoked Ca²⁺ influx and extracellular signal-regulated kinase phosphorylation in mouse astrocytes

Q/R Site Editing Controls Kainate Receptor Inhibition by Membrane Fatty Acids

Transplanted Neuroblasts Differentiate Appropriately into Projection Neurons with Correct Neurotransmitter and Receptor Phenotype in Neocortex Undergoing Targeted Projection Neuron Degeneration

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Developmental changes of RNA editing of glutamate receptor subunits GluR5 and GluR6: in vivo versus in vitro

Cited by 47 publications

References 41 publications

Fluoxetine affects GluK2 editing, glutamate-evoked Ca2+ influx and extracellular signal-regulated kinase phosphorylation in mouse astrocytes

Fluoxetine affects GluK2 editing, glutamate-evoked Ca2+ influx and extracellular signal-regulated kinase phosphorylation in mouse astrocytes

Q/R Site Editing Controls Kainate Receptor Inhibition by Membrane Fatty Acids

Transplanted Neuroblasts Differentiate Appropriately into Projection Neurons with Correct Neurotransmitter and Receptor Phenotype in Neocortex Undergoing Targeted Projection Neuron Degeneration

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Fluoxetine affects GluK2 editing, glutamate-evoked Ca²⁺ influx and extracellular signal-regulated kinase phosphorylation in mouse astrocytes

Fluoxetine affects GluK2 editing, glutamate-evoked Ca²⁺ influx and extracellular signal-regulated kinase phosphorylation in mouse astrocytes