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RESEARCH PRODUCT

Pgc-1α and Nr4a1 Are Target Genes of Circadian Melatonin and Dopamine Release in Murine Retina

Debra K. KelleherGianluca TosiniP. Michael IuvoneUwe WolfrumKenkichi BabaTanja WolloscheckRainer SpessertS. Anna SargsyanStefanie Kunst

subject

Malemedicine.medical_specialtyDopamineDNA Mutational AnalysisBiologyMelatonin receptorRetinaMelatoninMiceDopamineInternal medicinemedicineNuclear Receptor Subfamily 4 Group A Member 1AnimalsCircadian rhythmReceptorMelatoninRegulation of gene expressionDNAAdaptation PhysiologicalPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaeye diseasesCircadian RhythmMice Inbred C57BLEndocrinologyGene Expression RegulationDopamine receptorMutationFemalesense organsSignal transductionhormones hormone substitutes and hormone antagonistsmedicine.drugSignal TransductionTranscription Factors

description

Purpose 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.

10.1167/iovs.15-17503https://europepmc.org/articles/PMC4585341/