دورية أكاديمية
The transcription factor VAX1 in VIP neurons of the suprachiasmatic nucleus impacts circadian rhythm generation, depressive-like behavior, and the reproductive axis in a sex-specific manner in mice.
| العنوان: | The transcription factor VAX1 in VIP neurons of the suprachiasmatic nucleus impacts circadian rhythm generation, depressive-like behavior, and the reproductive axis in a sex-specific manner in mice. |
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| المؤلفون: | Van Loh BM; Department of Animal Science and the Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, MI, United States., Yaw AM; Department of Animal Science and the Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, MI, United States., Breuer JA; Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, United States., Jackson B; Department of Radiology and Precision Health Program, Michigan State University, East Lansing, MI, United States., Nguyen D; Department of Animal Science and the Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, MI, United States., Jang K; Department of Animal Science and the Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, MI, United States., Ramos F; Department of Animal Science and the Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, MI, United States., Ho EV; Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, United States., Cui LJ; Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, United States., Gillette DLM; Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, United States., Sempere LF; Department of Radiology and Precision Health Program, Michigan State University, East Lansing, MI, United States., Gorman MR; Department of Psychology, University of California, San Diego, La Jolla, CA, United States.; Center for Circadian Biology, University of California, San Diego, La Jolla, CA, United States., Tonsfeldt KJ; Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, United States.; Center for Circadian Biology, University of California, San Diego, La Jolla, CA, United States., Mellon PL; Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, United States.; Center for Circadian Biology, University of California, San Diego, La Jolla, CA, United States., Hoffmann HM; Department of Animal Science and the Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, MI, United States.; Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, United States. |
| المصدر: | Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2023 Dec 22; Vol. 14, pp. 1269672. Date of Electronic Publication: 2023 Dec 22 (Print Publication: 2023). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101555782 Publication Model: eCollection Cited Medium: Print ISSN: 1664-2392 (Print) Linking ISSN: 16642392 NLM ISO Abbreviation: Front Endocrinol (Lausanne) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Transcription Factors* , Neuropeptides*, Male ; Female ; Animals ; Mice ; Vasoactive Intestinal Peptide ; Kisspeptins/genetics ; Semen ; Suprachiasmatic Nucleus ; Reproduction ; Neurons ; Circadian Rhythm ; Gonadotropin-Releasing Hormone ; Homeodomain Proteins |
| مستخلص: | Background: The suprachiasmatic nucleus (SCN) within the hypothalamus is a key brain structure required to relay light information to the body and synchronize cell and tissue level rhythms and hormone release. Specific subpopulations of SCN neurons, defined by their peptide expression, regulate defined SCN output. Here we focus on the vasoactive intestinal peptide (VIP) expressing neurons of the SCN. SCN VIP neurons are known to regulate circadian rhythms and reproductive function. Methods: To specifically study SCN VIP neurons, we generated a novel knock out mouse line by conditionally deleting the SCN enriched transcription factor, Ventral Anterior Homeobox 1 (Vax1), in VIP neurons (Vax1 Vip ; Vax1 fl/fl :Vip Cre ). Results: We found that Vax1 Vip females presented with lengthened estrous cycles, reduced circulating estrogen, and increased depressive-like behavior. Further, Vax1 Vip males and females presented with a shortened circadian period in locomotor activity and ex vivo SCN circadian period. On a molecular level, the shortening of the SCN period was driven, at least partially, by a direct regulatory role of VAX1 on the circadian clock genes Bmal1 and Per2 . Interestingly, Vax1 Vip females presented with increased expression of arginine vasopressin ( Avp ) in the paraventricular nucleus, which resulted in increased circulating corticosterone. SCN VIP and AVP neurons regulate the reproductive gonadotropin-releasing hormone (GnRH) and kisspeptin neurons. To determine how the reproductive neuroendocrine network was impacted in Vax1 Vip mice, we assessed GnRH sensitivity to a kisspeptin challenge in vivo . We found that GnRH neurons in Vax1 Vip females, but not males, had an increased sensitivity to kisspeptin, leading to increased luteinizing hormone release. Interestingly, Vax1 Vip males showed a small, but significant increase in total sperm and a modest delay in pubertal onset. Both male and female Vax1 Vip mice were fertile and generated litters comparable in size and frequency to controls. Conclusion: Together, these data identify VAX1 in SCN VIP neurons as a neurological overlap between circadian timekeeping, female reproduction, and depressive-like symptoms in mice, and provide novel insight into the role of SCN VIP neurons. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Van Loh, Yaw, Breuer, Jackson, Nguyen, Jang, Ramos, Ho, Cui, Gillette, Sempere, Gorman, Tonsfeldt, Mellon and Hoffmann.) |
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| معلومات مُعتمدة: | R01 HD100580 United States HD NICHD NIH HHS; R25 NS090989 United States NS NINDS NIH HHS; R00 HD084759 United States HD NICHD NIH HHS; T32 HD007203 United States HD NICHD NIH HHS; T32 HD087166 United States HD NICHD NIH HHS; P42 ES010337 United States ES NIEHS NIH HHS; P30 DK063491 United States DK NIDDK NIH HHS; P50 HD028934 United States HD NICHD NIH HHS; K99 NS119291 United States NS NINDS NIH HHS; P30 CA023100 United States CA NCI NIH HHS; T32 GM008666 United States GM NIGMS NIH HHS; F32 HD107852 United States HD NICHD NIH HHS; P50 HD012303 United States HD NICHD NIH HHS; T32 GM007198 United States GM NIGMS NIH HHS; R01 HD072754 United States HD NICHD NIH HHS; R01 HD082567 United States HD NICHD NIH HHS; K99 HD084759 United States HD NICHD NIH HHS; F32 HD090837 United States HD NICHD NIH HHS |
| فهرسة مساهمة: | Keywords: arginine vasopressin; circadian rhythm; cortisol; premenstrual disorders; reproduction; suprachiasmatic nucleus; vasoactive intestinal peptide; ventral anterior homeobox 1 |
| المشرفين على المادة: | 0 (Transcription Factors) 37221-79-7 (Vasoactive Intestinal Peptide) 0 (Kisspeptins) 33515-09-2 (Gonadotropin-Releasing Hormone) 0 (Vax1 protein, mouse) 0 (Neuropeptides) 0 (Homeodomain Proteins) |
| تواريخ الأحداث: | Date Created: 20240111 Date Completed: 20240112 Latest Revision: 20240229 |
| رمز التحديث: | 20240301 |
| مُعرف محوري في PubMed: | PMC10777845 |
| DOI: | 10.3389/fendo.2023.1269672 |
| PMID: | 38205198 |
| قاعدة البيانات: | MEDLINE |
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