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• W2023402473 abstract "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." @default.
• W2023402473 created "2016-06-24" @default.
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• W2023402473 date "2014-03-24" @default.
• W2023402473 modified "2023-10-16" @default.
• W2023402473 title "Adaptive Gene Regulation in the Striatum of RGS9-Deficient Mice" @default.
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• W2023402473 doi "https://doi.org/10.1371/journal.pone.0092605" @default.
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