- AutorIn
- Kathy Busse
- Rainer Strotmann
- Karl Strecker
- Florian Wegner
- Vasudharani Devanathan
- Antje Gohla
- Torsten Schöneberg
- Johannes Schwarz
- Titel
- Adaptive gene regulation in the striatum of RGS9-deficient mice
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:15-qucosa-144141
- Quellenangabe
- PLOS One March, 24, 2014 doi: 10.1371/journal.pone.0092605
- Erstveröffentlichung
- 2014
- Abstract (EN)
- Background: RGS9-deficient mice show drug-induced dyskinesia but normal locomotor activity under unchallenged conditions. Results: Genes related to Ca2+ signaling and their functions were regulated in RGS9-deficient mice. Conclusion: Changes in Ca2+ signaling that compensate for RGS9 loss-of-function can explain the normal locomotor activity in RGS9-deficient mice under unchallenged conditions. Significance: Identified signaling components may represent novel targets in antidyskinetic therapy. The long splice variant of the regulator of G-protein signaling 9 (RGS9-2) is enriched in striatal medium spiny neurons and dampens dopamine D2 receptor signaling. Lack of RGS9-2 can promote while its overexpression prevents drug-induced dyskinesia. Other animal models of drug-induced dyskinesia rather pointed towards overactivity of dopamine receptor-mediated signaling. To evaluate changes in signaling pathways mRNA expression levels were determined and compared in wild-type and RGS9- deficient mice. Unexpectedly, expression levels of dopamine receptors were unchanged in RGS9-deficient mice, while several genes related to Ca2+ signaling and long-term depression were differentially expressed when compared to wild type animals. Detailed investigations at the protein level revealed hyperphosphorylation of DARPP32 at Thr34 and of ERK1/2 in striata of RGS9-deficient mice. Whole cell patch clamp recordings showed that spontaneous synaptic events are increased (frequency and size) in RGS9-deficient mice while long-term depression is reduced in acute brain slices. These changes are compatible with a Ca2+-induced potentiation of dopamine receptor signaling which may contribute to the drug-induced dyskinesia in RGS9-deficient mice.
- Andere Ausgabe
- Link zur Originalpublikation in der Zeitschrift PLoS ONE
Link: http://dx.doi.org/10.1371/journal.pone.0092605 - Freie Schlagwörter (DE)
- G-Protein, Signal, Proteinkinase, Maus
- Freie Schlagwörter (EN)
- G-protein signaling, Protein kinase signaling, mouse
- Klassifikation (DDC)
- 610
- Herausgeber (Institution)
- Universität Leipzig
- Universität Tübingen
- Universität Würzburg
- Technische Universität München
- Verlag
- Public Library of Science, San Francisco, Calif.
- URN Qucosa
- urn:nbn:de:bsz:15-qucosa-144141
- Veröffentlichungsdatum Qucosa
- 27.05.2014
- Dokumenttyp
- Artikel
- Sprache des Dokumentes
- Englisch
- Inhaltsverzeichnis
Introduction; Materials and methods; Results; Discussion