title: Dopaminergic regulation of olfactory type G-protein α subunit expression in the striatum.
abstract: BACKGROUND
  In rodents, the olfactory type G-protein α subunit (Gαolf) couples the dopamine D1 receptor (D1R) to adenylyl cyclase, triggering intracellular signaling and neuronal activation. In the striatum, Gαolf is enriched in the striosomes. Changes in Gαolf protein levels have been observed after dopamine depletion. However, the regulation of Gαolf expression by dopamine and dopamine receptors is not fully understood.
  
  
  METHODS
  To address this, Striatal Gαolf expression pattern was studied in wild-type and genetically engineered mice lacking D1R, D2R (D2 receptor), and downstream regulatory element antagonist modulator (DREAM) protein whose dopamine levels were manipulated. Dopamine depletion was accomplished by 6-hydroxydopamine (6-OHDA) or by Pitx3 ablation, and dopamine replacement by chronic levodopa (l-dopa). The Gαolf levels were analyzed by immunohistochemistry, Western blot, and real-time quantitative polymerase chain reaction (RT-qPCR).
  
  
  RESULTS
  Our results demostrate that Dopamine depletion or inactivation of D1R abolished the striosomal pattern of Gαolf expression and increased Gαolf protein levels. Dopamine replacement in wild-type lesioned mice reestablished both the expression pattern and protein levels, but paradoxically increased Gαolf messenger RNA (mRNA). In D1R(-/-) mice, dopamine depletion decreased striatal Gαolf expression, whereas l-dopa did not restore either Gαolf levels or its expression pattern. Inactivation of D2R or changes in the cAMP/PKA signaling pathway downstream of Gαolf did not modify its expression.
  
  
  CONCLUSIONS
  Our results show a homeostatic, negative regulation of Gαolf by dopamine and by D1R stimulation, which are also required for the striosomal Gαolf pattern. These results shed light on the regulation of Gαolf by dopamine signaling that could be involved in the pathophysiology of the maladaptive response to chronic l-dopa treatment in Parkinson's disease.
authors.affiliation: Cajal Institute, Consejo Superior de Investigaciones Científicas (CSIC), CIBERNED, Madrid, Spain.|CIBERNED, Instituto de Salud Carlos III, CIBERNED, Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Ruiz-DeDiego
authors.affiliation: CIBERNED, Instituto de Salud Carlos III, CIBERNED, Madrid, Spain.|Centro Nacional de Biotecnología, CSIC, Madrid, Spain.
authors.forename: J R
authors.initials: JR
authors.lastname: Naranjo
authors.affiliation: Inserm UMR S-839, CIBERNED, Madrid, Spain.|Institut du Fer à Moulin, CIBERNED, Madrid, Spain.|Université Pierre et Marie Curie, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Hervé
authors.affiliation: Cajal Institute, Consejo Superior de Investigaciones Científicas (CSIC), CIBERNED, Madrid, Spain.|CIBERNED, Instituto de Salud Carlos III, CIBERNED, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Moratalla
mesh_terms: D000818:Animals; D004298:Dopamine / Q000172:deficiency / Q000378:metabolism*; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D017072:Neostriatum / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C583261:Drd1 protein, mouse; D044385:GTP-Binding Protein alpha Subunits; D017447:Receptors, Dopamine D1; C084618:olfactory G protein subunit alpha olf; D004298:Dopamine
keywords: AIMs; Parkinson's disease; dopaminergic receptors; l-dopa; striosomes