GluR‐ and TrkB‐mediated maturation of GABA<sub>A</sub> receptor function during the period of eye opening

Henneberger, Christian; Jüttner, René; Schmidt, Sonja; Walter, Jan; Meier, Jochen C.; Rothe, Thomás; Grantyn, Rosemarie

doi:10.1111/j.1460-9568.2005.03869.x

Cited by 30 publications

(29 citation statements)

References 67 publications

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“…Similarly, NTRK2 upregulation also confirm earlier reports that neutropin signaling is activated by antidepressant treatments. 21,109,113,114 This, together with the finding that ECS and SD elevate the levels Ania-4, Erg-2, Homer1, Hspb and Ret may reflect the growing assertion that antidepressant treatments are associated with neuroprotection, neurogenesis and neuronal plasticity. [10][11][12][13][14] A very limited number of transcripts was found to be affected by all three antidepressant treatments and only functional validation will reveal their relevance with respect to depression.…”

Section: Resultsmentioning

confidence: 95%

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

et al. 2006

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The significant proportion of depressed patients that are resistant to monoaminergic drug therapy and the slow onset of therapeutic effects of the selective serotonin reuptake inhibitors (SSRIs)/serotonin/noradrenaline reuptake inhibitors (SNRIs) are two major reasons for the sustained search for new antidepressants. In an attempt to identify common underlying mechanisms for fast-and slow-acting antidepressant modalities, we have examined the transcriptional changes in seven different brain regions of the rat brain induced by three clinically effective antidepressant treatments: electro convulsive therapy (ECT), sleep deprivation (SD), and fluoxetine (FLX), the most commonly used slow-onset antidepressant. Each of these antidepressant treatments was applied with the same regimen known to have clinical efficacy: 2 days of ECT (four sessions per day), 24 h of SD, and 14 days of daily treatment of FLX, respectively. Transcriptional changes were evaluated on RNA extracted from seven different brain regions using the Affymetrix rat genome microarray 230 2.0. The gene chip data were validated using in situ hybridization or autoradiography for selected genes. The major findings of the study are:1. The transcriptional changes induced by SD, ECT and SSRI display a regionally specific distribution distinct to each treatment. 2. The fast-onset, short-lived antidepressant treatments ECT and SD evoked transcriptional changes primarily in the catecholaminergic system, whereas the slow-onset antidepressant FLX treatment evoked transcriptional changes in the serotonergic system. 3. ECT and SD affect in a similar manner the same brain regions, primarily the locus coeruleus, whereas the effects of FLX were primarily in the dorsal raphe and hypothalamus, suggesting that both different regions and pathways account for fast onset but short lasting effects as compared to slow-onset but long-lasting effects. However, the similarity between effects of ECT and SD is somewhat confounded by the fact that the two treatments appear to regulate a number of transcripts in an opposite manner. 4. Multiple transcripts (e.g. brain-derived neurotrophic factor (BDNF), serum/glucocorticoidregulated kinase (Sgk1)), whose level was reported to be affected by antidepressants or behavioral manipulations, were also found to be regulated by the treatments used in the present study. Several novel findings of transcriptional regulation upon one, two or all three treatments were made, for the latter we highlight homer, erg2, HSP27, the proto oncogene ret, sulfotransferase family 1A (Sult1a1), glycerol 3-phosphate dehydrogenase (GPD3), the orphan receptor G protein-coupled receptor 88 (GPR88) and a large number of expressed sequence tags (ESTs). 5. Transcripts encoding proteins involved in synaptic plasticity in the hippocampus were strongly affected by ECT and SD, but not by FLX.The novel transcripts, concomitantly regulated by several antidepressant treatments, may represent novel targets for fast onset, long-duration antidepressants.

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Section: Resultsmentioning

confidence: 95%

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

et al. 2006

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“…Kainate receptor expression depends on activity in postnatal rat thalamocortical synapses (7). Electrical activity also regulates subunit expression of GABA A receptors (GABA A Rs) in rat superior colliculus neurons (8) and ACh receptors (AChRs) at the neonatal mouse neuromuscular junction (NMJ) (9).…”

mentioning

confidence: 99%

Activity-dependent neurotransmitter-receptor matching at the neuromuscular junction

Borodinsky

Spitzer

2007

Proc. Natl. Acad. Sci. U.S.A.

109

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Signaling in the nervous system requires matching of neurotransmitter receptors with cognate neurotransmitters at synapses. The vertebrate neuromuscular junction is the best studied cholinergic synapse, but the mechanisms by which acetylcholine is matched with acetylcholine receptors are not fully understood. Because alterations in neuronal calcium spike activity alter transmitter specification in embryonic spinal neurons, we hypothesized that receptor expression in postsynaptic cells follows changes in transmitter expression to achieve this specific match. We find that embryonic vertebrate striated muscle cells normally express receptors for glutamate, GABA, and glycine as well as for acetylcholine. As maturation progresses, acetylcholine receptor expression prevails. Receptor selection is altered when early neuronal calcium-dependent activity is perturbed, and remaining receptor populations parallel changes in transmitter phenotype. In these cases, glutamatergic, GABAergic, and glycinergic synaptic currents are recorded from muscle cells, demonstrating that activity regulates matching of transmitters and their receptors in the assembly of functional synapses.

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“…These early receptors containing ␣3 activate and deactivate more slowly than receptors composed of other ␣ subunits. Mechanisms by which the NMDA receptor activity controls the subunit switch have been suggested (38). However, the detailed mechanism underlying the developmental change is unclear.…”

Section: Discussionmentioning

confidence: 99%

Adenosine-to-Inosine RNA Editing Affects Trafficking of the γ-Aminobutyric Acid Type A (GABAA) Receptor

Daniel

Wahlstedt

Ohlson

et al. 2011

Journal of Biological Chemistry

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Recoding by adenosine-to-inosine RNA editing plays an important role in diversifying proteins involved in neurotransmission. We have previously shown that the Gabra-3 transcript, coding for the ␣3 subunit of the GABA A receptor is edited in mouse, causing an isoleucine to methionine (I/M) change. Here we show that this editing event is evolutionarily conserved from human to chicken. Analyzing recombinant GABA A receptor subunits expressed in HEK293 cells, our results suggest that editing at the I/M site in ␣3 has functional consequences on receptor expression. We demonstrate that I/M editing reduces the cell surface and the total number of ␣3 subunits. The reduction in cell surface levels is independent of the subunit combination as it is observed for ␣3 in combination with either the ␤2 or the ␤3 subunit. Further, an amino acid substitution at the corresponding I/M site in the ␣1 subunit has a similar effect on cell surface presentation, indicating the importance of this site for receptor trafficking. We show that the I/M editing during brain development is inversely related to the ␣3 protein abundance. Our results suggest that editing controls trafficking of ␣3-containing receptors and may therefore facilitate the switch of subunit compositions during development as well as the subcellular distribution of ␣ subunits in the adult brain. Adenosine to inosine (A-to-I)2 RNA editing is a mechanism used in the mammalian nervous system to provide alterations in the protein sequence by co-transcriptional modification of single nucleotides. This modification is catalyzed by adenosine deaminases that act on RNA (ADAR1 and ADAR2) that can selectively modify adenosine to inosine residues within double stranded pre-mRNAs. Within mRNA transcripts, inosine is read as guanosine by the translation machinery. Therefore, this mechanism has the potential to change the amino acid sequence and thereby the function of the protein. Several gene products encoding proteins involved in neurotransmission have been shown to be A-to-I edited, including ligand-and voltage-gated ion channels as well as a G-proteincoupled receptor and thereby creating diverse isoforms of proteins essential for balanced neuronal kinetics (reviewed in Ref. 1).One of the most well studied substrates for editing in the brain is the transcript coding for the AMPA glutamate receptor (GluA). AMPA receptors consist of four subunits (GluA1-GluA4) in different combinations. Changing a codon for glutamine to arginine in GluA2 is essential to the organism and required for a normal brain development (2, 3).We have previously found that the mouse Gabra-3 transcript, coding for the ␣3 subunit of the GABA A receptor undergoes site-selective A-to-I editing causing an isoleucine to methionine (I/M) change in the third transmembrane region (TM3) (4). The chloride-permeable (GABA A ) receptors are the main mediators of fast inhibitory neurotransmission in the mammalian central nervous system (reviewed in Ref. 5). These heteropentameric ligand-gated chloride ion channels can be f...

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GluR‐ and TrkB‐mediated maturation of GABA_A receptor function during the period of eye opening

Cited by 30 publications

References 67 publications

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

Activity-dependent neurotransmitter-receptor matching at the neuromuscular junction

Adenosine-to-Inosine RNA Editing Affects Trafficking of the γ-Aminobutyric Acid Type A (GABAA) Receptor

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GluR‐ and TrkB‐mediated maturation of GABAA receptor function during the period of eye opening

Cited by 30 publications

References 67 publications

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

Activity-dependent neurotransmitter-receptor matching at the neuromuscular junction

Adenosine-to-Inosine RNA Editing Affects Trafficking of the γ-Aminobutyric Acid Type A (GABAA) Receptor

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GluR‐ and TrkB‐mediated maturation of GABA_A receptor function during the period of eye opening