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Role of Leptin and Orexin-A Within the Suprachiasmatic Nucleus on Anxiety-Like Behaviors in Hamsters

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Abstract

It is well established that the maintenance of energy expenditure is linked to active hypothalamic neural mechanisms controlling adaptive stimuli such as food intake. Variations of glucose levels and hormonal (leptin plus orexin-A) parameters, which are involved with energy homeostasis during different behavioral states, have not yet been fully defined. In this first study, behavioral analyses of an unpredictable stress model dealing with the actions of a sub-chronic administration of orexin-A (ORX-A) and the anti-hunger neuropeptide, i.e., leptin (LEP) within the hypothalamic suprachiasmatic (SCH) nucleus, were conducted on the valuable hibernating rodent (hamster; Mesocricetus auratus) model noted for its distinct depression and anxiety states. Treatment with LEP accounted for a notable reduction (p < 0.01) of body weight in stressed hamsters that not only executed very evident (p < 0.001) movements to and from elevated plus maze (EPM) but also spent less time in the dark area of the light–dark box test (LDT). Conversely, ORX-A predominantly evoked anxiogenic effects that were inverted by LEP. Interestingly, the anti-hunger neuropeptide accounted for both down-regulated NPY1 transcripts in mostly lateral-posterior hypothalamic areas while up-regulated levels were detected in the parietal cerebral cortex, hippocampus, and amygdala, which largely behaved in an opposite manner to ORX-A-dependent effects. Overall, the present findings corroborate a predominating LEPergic effect of the SCH toward the reduction of hamster anxiety-like behaviors with respect to that of ORX-A signaling, which may constitute useful therapeutic targets for stress-related obesity states.

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Abbreviations

AMY:

Amygdala

ANOVA:

Analysis of variance

COR:

Cerebral cortex

CRH:

Corticotropin-releasing hormone

EPM:

Elevated plus maze

HIP:

Hippocampus

HTH:

Hypothalamus

ISH:

In situ hybridization

LDT:

Light–dark box test

LEP:

Leptin

ORX-A:

Orexin-A

SCH:

Hypothalamic suprachiasmatic nucleus

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Acknowledgments

This work was funded by Italian University Research Ministry (MIUR).

Author Contributions

RA and MC conceived and designed the experiments. RA, EA, MM, and FG performed the experiments. RA, MC, RMF, and AC analyzed the data. RA and MC wrote the paper. RA supervised the experiment.

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Authors and Affiliations

  1. Comparative Neuroanatomy Laboratory, Biology, Ecology and Earth Science Department (DiBEST), University of Calabria, Ponte Pietro Bucci 4B, Arcavacata di Rende, 87030, Cosenza, Italy

    Raffaella Alò, Ennio Avolio, Maria Mele, Gilda Fazzari, Antonio Carelli, Rosa Maria Facciolo & Marcello Canonaco

  2. Health Center srl, Biomedical and Nutritional Center, via Sabotino 66, 87100, Cosenza, Italy

    Ennio Avolio

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  1. Raffaella Alò
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  2. Ennio Avolio
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Correspondence to Raffaella Alò.

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Research Involving Animals

Animal maintenance and experimental procedures were carried out in compliance with the ethical provisions for Care and Use of Laboratory Animals reported in the legislative law no. 116 (27-01-1992) and authorized by the National Committee of the Italian Ministry of Health. The protocol was approved by the Scientific Committee of Biology, Ecology and Earth Science Department (DiBEST), University of Calabria, Italy (2015). All efforts were made to minimize animal suffering and to reduce the number of animals used.

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Alò, R., Avolio, E., Mele, M. et al. Role of Leptin and Orexin-A Within the Suprachiasmatic Nucleus on Anxiety-Like Behaviors in Hamsters. Mol Neurobiol 54, 2674–2684 (2017). https://doi.org/10.1007/s12035-016-9847-9

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