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This research was funded by the Federacion Espanola de Enfermedades Raras (FEDER FI9058) and Eugenio Rodriguez Pascual Foundation (FERP2021). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Analysis of institutional authors

Carrera-Canas, CarlosAuthorDe Andres, IsabelAuthorGarzon, MiguelCorresponding Author

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Plasticity of the hypocretinergic/orexinergic system after a chronic treatment with suvorexant in rats. Role of the hypocretinergic/orexinergic receptor 1 as an autoreceptor

Publicated to:Frontiers in Molecular Neuroscience. 15 1013182- - 2022-10-05 15(), DOI: 10.3389/fnmol.2022.1013182

Authors: Carrera-Canas, Carlos; de Andres, Isabel; Callejo, Marta; Garzon, Miguel;

Affiliations

Univ Autonoma Madrid, Fac Med, Dept Anat Histol & Neurociencia, Madrid, Spain - Author

Abstract

The hypothalamic hypocretinergic/orexinergic (Hcrt/Ox) system is involved in many physiological and pathophysiological processes. Malfunction of Hcrt/Ox transmission results in narcolepsy, a sleep disease caused in humans by progressive neurodegeneration of hypothalamic neurons containing Hcrt/Ox. To explore the Hcrt/Ox system plasticity we systemically administered suvorexant (a dual Hcrt/Ox receptor antagonist) in rats to chronically block Hcrt/Ox transmission without damaging Hcrt/Ox cells. Three groups of eight rats (four males and four females) received daily i.p. injections of suvorexant (10 or 30 mg/kg) or vehicle (DMSO) over a period of 7 days in which the body weight was monitored. After the treatments cerebrospinal fluid (CSF) Hcrt1/OxA concentration was measured by ELISA, and hypothalamic Hcrt/OxR1 and Hcrt/OxR2 levels by western blot. The systemic blockade of the Hcrt/Ox transmission with the suvorexant high dose produced a significant increase in body weight at the end of the treatment, and a significant decrease in CSF Hcrt1/OxA levels, both features typical in human narcolepsy type 1. Besides, a significant overexpression of hypothalamic Hcrt/OxR1 occurred. For the Hcrt/OxR2 two very close bands were detected, but they did not show significant changes with the treatment. Thus, the plastic changes observed in the Hcrt/Ox system after the chronic blockade of its transmission were a decrease in CSF Hcrt1/OXA levels and an overexpression of hypothalamic Hcrt/OxR1. These findings support an autoregulatory role of Hcrt/OxR1 within the hypothalamus, which would induce the synthesis/release of Hcrt/Ox, but also decrease its own availability at the plasma membrane after binding Hcrt1/OxA to preserve Hcrt/Ox system homeostasis.

Keywords

dorashypocretinhypothalamusnarcolepsyorexinDeficiencyDorasExpressionHypocretinHypocretin orexinHypothalamusNarcolepsyNeuronsOrexinPeptidesPrepro-orexinRemSleepSuvorexant

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Frontiers in Molecular Neuroscience due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Molecular Biology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 1.08, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-15, the following number of citations:

  • WoS: 1
  • Scopus: 1
  • Europe PMC: 1
  • OpenCitations: 1

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-15:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 7.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 7 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 2.95.
  • The number of mentions on the social network X (formerly Twitter): 4 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://repositorio.uam.es/handle/10486/712178

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (CARRERA CAÑAS, CARLOS) and Last Author (GARZON GARCIA, MIGUEL).

the author responsible for correspondence tasks has been GARZON GARCIA, MIGUEL.