title: Pgc-1α and Nr4a1 Are Target Genes of Circadian Melatonin and Dopamine Release in Murine Retina.
abstract: OBJECTIVE
  The neurohormones melatonin and dopamine mediate clock-dependent/circadian regulation of inner retinal neurons and photoreceptor cells and in this way promote their functional adaptation to time of day and their survival. To fulfill this function they act on melatonin receptor type 1 (MT1 receptors) and dopamine D4 receptors (D4 receptors), respectively. The aim of the present study was to screen transcriptional regulators important for retinal physiology and/or pathology (Dbp, Egr-1, Fos, Nr1d1, Nr2e3, Nr4a1, Pgc-1α, Rorβ) for circadian regulation and dependence on melatonin signaling/MT1 receptors or dopamine signaling/D4 receptors.
  
  
  METHODS
  This was done by gene profiling using quantitative polymerase chain reaction in mice deficient in MT1 or D4 receptors.
  
  
  RESULTS
  The data obtained determined Pgc-1α and Nr4a1 as transcriptional targets of circadian melatonin and dopamine signaling, respectively.
  
  
  CONCLUSIONS
  The results suggest that Pgc-1α and Nr4a1 represent candidate genes for linking circadian neurohormone release with functional adaptation and healthiness of retina and photoreceptor cells.
authors.affiliation: Institute of Functional and Clinical Anatomy University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany 2Department of Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kunst
authors.affiliation: Institute of Functional and Clinical Anatomy University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Wolloscheck
authors.affiliation: Institute of Functional and Clinical Anatomy University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Debra K
authors.initials: DK
authors.lastname: Kelleher
authors.affiliation: Department of Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Wolfrum
authors.affiliation: Departments of Ophthalmology and Pharmacology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: S Anna
authors.initials: SA
authors.lastname: Sargsyan
authors.affiliation: Departments of Ophthalmology and Pharmacology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: P Michael
authors.initials: PM
authors.lastname: Iuvone
authors.affiliation: Neuroscience Institute and Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, Georgia, United States.
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Baba
authors.affiliation: Neuroscience Institute and Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, Georgia, United States.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tosini
authors.affiliation: Institute of Functional and Clinical Anatomy University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Spessert
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics* / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D014157:Transcription Factors; D004247:DNA; D008550:Melatonin; D004298:Dopamine