title: The role of PPARβ/δ in the regulation of glutamatergic signaling in the hamster suprachiasmatic nucleus.
abstract: Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily and function as transcription factors that regulate gene expression in numerous biological processes. Although the PPARβ/δ subtype is highly expressed in the brain, its physiological roles in neuronal function remain to be elucidated. In this study, we examined the presence of PPARβ/δ in the master circadian clock of the Syrian hamster and investigated its putative functional role in this structure. In mammals, the central circadian clock, located in the suprachiasmatic nucleus (SCN), is entrained by the light-dark (LD) cycle via photic6 signals conveyed by a direct pathway whose terminals release glutamate. Using immunocytochemical and qRT-PCR analysis, we demonstrated that the rhythmic expression of PPAR β/δ within the SCN of hamsters raised under an LD cycle was detectable only at the transcriptional level when the hamsters were maintained under constant darkness (DD). The increase in the number of immunoreactive PPARβ/δ cells observed under DD after light stimulation during the early subjective night (CT14), but not during the subjective day (CT06), demonstrated that the expression of PPARβ/δ can be up-regulated according to the photosensitive phase of the circadian clock. All of the PPARβ/δ-positive cells in the SCN also expressed the glutamate receptor NMDAR1. Moreover, we demonstrated that at the photosensitive point (CT14), the administration of L-16504, a specific agonist of PPARβ/δ, amplified the phase delay of the locomotor response induced by a light pulse. Taken together, these data suggest that PPARβ/δ activation modulates glutamate release that mediates entrainment of the circadian clock by light.
authors.affiliation: Department of Neurobiology of Rhythms, Institute of Cellular and Integrative Neurosciences, UPR 3212 CNRS, University of Strasbourg, 67084 Strasbourg cedex, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Challet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Denis
authors.forename: Violaine
authors.initials: V
authors.lastname: Rochet
authors.forename: Josiane
authors.initials: J
authors.lastname: Aïoun
authors.forename: Sylviane
authors.initials: S
authors.lastname: Gourmelen
authors.forename: Herminie
authors.initials: H
authors.lastname: Lacroix
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Goustard-Langelier
authors.forename: Catherine
authors.initials: C
authors.lastname: Papillon
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Alessandri
authors.forename: Monique
authors.initials: M
authors.lastname: Lavialle
mesh_terms: D000818:Animals; D002940:Circadian Rhythm; D006224:Cricetinae; D003624:Darkness; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D008027:Light; D055537:Light Signal Transduction; D008647:Mesocricetus; D047494:PPAR delta / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D048068:PPAR-beta / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D010642:Phenoxyacetates / Q000494:pharmacology; D017440:Photoperiod; D060888:Real-Time Polymerase Chain Reaction; D013493:Suprachiasmatic Nucleus / Q000378:metabolism* / Q000528:radiation effects
chemical_list: D047494:PPAR delta; D048068:PPAR-beta; D010642:Phenoxyacetates; D018698:Glutamic Acid