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1.
Exp Eye Res ; 244: 109943, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38797259

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.


Subject(s)
Hypothalamus , Orexin Receptors , Pituitary Adenylate Cyclase-Activating Polypeptide , Proto-Oncogene Proteins c-fos , Rats, Wistar , Retina , Vasoactive Intestinal Peptide , Animals , Male , Rats , Proto-Oncogene Proteins c-fos/metabolism , Proto-Oncogene Proteins c-fos/genetics , Hypothalamus/metabolism , Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism , Pituitary Adenylate Cyclase-Activating Polypeptide/genetics , Orexin Receptors/metabolism , Orexin Receptors/genetics , Retina/metabolism , Vasoactive Intestinal Peptide/metabolism , Naphthyridines , ARNTL Transcription Factors/genetics , ARNTL Transcription Factors/metabolism , Gene Expression Regulation , Orexin Receptor Antagonists/pharmacology , Benzoxazoles/pharmacology , Urea/analogs & derivatives , Urea/pharmacology , Circadian Rhythm/physiology , Suprachiasmatic Nucleus/metabolism , Dioxanes , Isoquinolines , Phenylurea Compounds , Pyridines
2.
Gen Comp Endocrinol ; 337: 114242, 2023 06 01.
Article in English | MEDLINE | ID: mdl-36801394

ABSTRACT

Orexins A and B (OXA and OXB) and their receptors are expressed in the retina of both human and rodents and play a vital role in regulating signal transmission circuits in the retina. There is an anatomical-physiological relationship between the retinal ganglion cells and suprachiasmatic nucleus (SCN) through glutamate as a neurotransmitter and retinal pituitary adenylate cyclase-activating polypeptide (PACAP) as a co-transmitter. SCN is the main brain center for regulating the circadian rhythm, which governs the reproductive axis. The impact of retinal orexin receptors on the hypothalamic-pituitary-gonadal axis has not been investigated. Retinal OX1R or/and OX2R in adult male rats by 3 µl of SB-334867 (1 µg) or/and 3 µl of JNJ-10397049 (2 µg) were antagonized via intravitreal injection (IVI). Four time-periods were considered (3, 6, 12, and 24 h) for the controls without any treatment, SB-334867, JNJ-10397049, and SB-334867 + JNJ-10397049 groups. Antagonizing retinal OX1R or/and OX2R resulted in a significant elevation of retinal PACAP expression compared to control animals. In addition, expression of GnRH increased non-significantly in the hypothalamus over the 6 h of the study, and the serum concentration of LH decreased significantly in the SB-334867 group after 3 h of injection. Furthermore, testosterone serum levels declined significantly, especially within 3 h of injection; serum levels of progesterone were also exposed to a significant rise at least within 3 h of injection. However, the retinal PACAP expression changes were mediated by OX1R more effectively than by OX2R. In this study, we report the retinal orexins and their receptors as light-independent factors by which the retina affects the hypothalamic-pituitary-gonadal axis.


Subject(s)
Hypothalamic-Pituitary-Gonadal Axis , Pituitary Adenylate Cyclase-Activating Polypeptide , Rats , Male , Humans , Animals , Pituitary Adenylate Cyclase-Activating Polypeptide/pharmacology , Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism , Rats, Wistar , Orexin Receptors/metabolism , Orexins/metabolism , Retina , Rodentia/metabolism
3.
PLoS One ; 17(8): e0271264, 2022.
Article in English | MEDLINE | ID: mdl-36044463

ABSTRACT

BACKGROUND: In Jordan, cancer is the second leading cause of death after cardiac disease. The impact of cancer on sexual relationships is a taboo subject and hence, such issues are underreported research among Jordanian people examining unmet needs. AIM: To examine the experiences and preferences of Jordanian cancer survivors related to communication regarding their sexual needs. METHODS: Qualitative study conducted between May and June 2020 using semi-structured face-to-face interviews using the snow-balling approach for recruitment. Participants were recruited until data saturation was obtained and data were analyzed using qualitative thematic analysis. RESULTS: Analysis of participants' interview data identified three main categories: 1) The psychological impact of cancer of sexual relationships; 2) Physician support; 3) Variations in sexual life and sexual experiences. CONCLUSION: The study revealed that there is a substantial psychological impact of cancer on sexual relationships among Arab Jordanian cancer survivors. Feeling powerless, being labelled as 'sexually disabled', and lack of communication with physicians were emphasized by participants as a barrier to discuss sexual needs with their physicians. Lack of physicians support negatively impact Jordanian cancer survivors sexual experience and led to increased their sense of powerlessness and loss of control over sexual relationships. IMPLICATIONS FOR PRACTICE: Overall, the study indicated a crucial need for physicians to encourage patients to disclose their sexual experience to help them maintain their sexual and mental health while in the fight against cancer. The physicians, nurses and allied health professionals should be engaged in the conversation with patients by taking an active role in the discussion. Additionally, the family and partners of the patients should also be approached and engaged by health professionals in the discussion to address their needs or sexual issues.


Subject(s)
Cancer Survivors , Neoplasms , Arabs , Humans , Jordan , Qualitative Research , Sexual Behavior/psychology
4.
Int J Fertil Steril ; 15(4): 246-251, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34913291

ABSTRACT

Monosodium glutamate (MSG) is a flavour enhancer that is used as a food additive (E621) in many parts of the world, especially in East Asian countries. However, in recent studies, it has been used as a neurotoxin because MSG is reported to cause neural degeneration in the hypothalamic arcuate of neonatal animals. The results of several studies show the negative effects of MSG injections on different parts of the hypothalamic-pituitary-gonadal (HPG) axis, in addition to its ability to inhibit secretion many reproductive neuropeptides, neurotrophic factors, and hormones, all of which play vital roles in the regulation of reproductive function. Oral administration or injection of large quantities of MSG into newborn animals results in a decrease in or overabundance of the production of many regulatory peptides of the male and female reproductive systems. In this review, we summarize the results of the most important studies that have examined the effect of oral consumption or injection of MSG on regulatory peptides of the HPG axis.

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