The differential effects of blocking retinal orexin receptors on the expression of retinal c-fos and hypothalamic Vip, PACAP, Bmal1, and c-fos in Male Wistar Rats.

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  • Additional Information
    • Source:
      Publisher: Academic Press Country of Publication: England NLM ID: 0370707 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0007 (Electronic) Linking ISSN: 00144835 NLM ISO Abbreviation: Exp Eye Res Subsets: MEDLINE
    • Publication Information:
      Publication: London : Academic Press
      Original Publication: London.
    • Subject Terms:
      Hypothalamus*/metabolism ; Orexin Receptors*/metabolism ; Orexin Receptors*/genetics ; Pituitary Adenylate Cyclase-Activating Polypeptide*/metabolism ; Pituitary Adenylate Cyclase-Activating Polypeptide*/genetics ; Proto-Oncogene Proteins c-fos*/metabolism ; Proto-Oncogene Proteins c-fos*/genetics ; Retina*/metabolism ; Vasoactive Intestinal Peptide*/metabolism; Animals ; Male ; Rats ; ARNTL Transcription Factors/genetics ; ARNTL Transcription Factors/metabolism ; Benzoxazoles/pharmacology ; Circadian Rhythm/physiology ; Dioxanes ; Gene Expression Regulation ; Isoquinolines ; Naphthyridines ; Orexin Receptor Antagonists/pharmacology ; Phenylurea Compounds ; Pyridines ; Rats, Wistar ; Suprachiasmatic Nucleus/metabolism ; Urea/analogs & derivatives ; Urea/pharmacology
    • Abstract:
      Orexin A and B (OXA and OXB) and their receptors are expressed in the majority of retinal neurons in humans, rats, and mice. Orexins modulate signal transmission between the different layers of the retina. The suprachiasmatic nucleus (SCN) and the retina are central and peripheral components of the body's biological clocks; respectively. The SCN receives photic information from the retina through the retinohypothalamic tract (RHT) to synchronize bodily functions with environmental changes. In present study, we aimed to investigate the impact of inhibiting retinal orexin receptors on the expression of retinal Bmal1 and c-fos, as well as hypothalamic c-fos, Bmal1, Vip, and PACAP at four different time-points (Zeitgeber time; ZT 3, 6, 11, and ZT-0). The intravitreal injection (IVI) of OX1R antagonist (SB-334867) and OX2R antagonist (JNJ-10397049) significantly up-regulated c-fos expression in the retina. Additionally, compared to the control group, the combined injection of SB-334867 and JNJ-10397049 showed a greater increase in retinal expression of this gene. Moreover, the expression of hypothalamic Vip and PACAP was significantly up-regulated in both the SB-334867 and JNJ-10397049 groups. In contrast, the expression of Bmal1 was down-regulated. Furthermore, the expression of hypothalamic c-fos was down-regulated in all groups treated with SB-334867 and JNJ-10397049. Additionally, the study demonstrated that blocking these receptors in the retina resulted in alterations in circadian rhythm parameters such as mesor, amplitude, and acrophase. Finally, it affected the phase of gene expression rhythms in both the retina and hypothalamus, as identified through cosinor analysis and the zero-amplitude test. This study represents the initial exploration of how retinal orexin receptors influence expression of rhythmic genes in the retina and hypothalamus. These findings could provide new insights into how the retina regulates the circadian rhythm in both regions and illuminate the role of the orexinergic system expression within the retina.
      Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.
      (Copyright © 2024. Published by Elsevier Ltd.)
    • Contributed Indexing:
      Keywords: Circadian rhythm; Hypothalamus; Intravitreal injection; Orexin receptors; Retina
    • Accession Number:
      0 (1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea)
      0 (1-(3,4-dihydro-6,7-dimethoxy-2(1H)-isoquinolinyl)-3,3-dimethyl-2-((4-pyridinylmethyl)amino)-1-butanone)
      0 (Arntl protein, rat)
      0 (ARNTL Transcription Factors)
      0 (Benzoxazoles)
      0 (Dioxanes)
      0 (Isoquinolines)
      0 (JNJ 10397049)
      0 (Naphthyridines)
      0 (Orexin Receptor Antagonists)
      0 (Orexin Receptors)
      0 (Phenylurea Compounds)
      0 (Pituitary Adenylate Cyclase-Activating Polypeptide)
      0 (Proto-Oncogene Proteins c-fos)
      0 (Pyridines)
      8W8T17847W (Urea)
      37221-79-7 (Vasoactive Intestinal Peptide)
    • Publication Date:
      Date Created: 20240526 Date Completed: 20240614 Latest Revision: 20240716
    • Publication Date:
      20240716
    • Accession Number:
      10.1016/j.exer.2024.109943
    • Accession Number:
      38797259