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Characterization of the Thermoregulatory Response to Pituitary Adenylate Cyclase-Activating Polypeptide in Rodents

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Abstract

Administration of the long form (38 amino acids) of pituitary adenylate cyclase-activating polypeptide (PACAP38) into the central nervous system causes hyperthermia, suggesting that PACAP38 plays a role in the regulation of deep body temperature (T b). In this study, we investigated the thermoregulatory role of PACAP38 in details. First, we infused PACAP38 intracerebroventricularly to rats and measured their T b and autonomic thermoeffector responses. We found that central PACAP38 infusion caused dose-dependent hyperthermia, which was brought about by increased thermogenesis and tail skin vasoconstriction. Compared to intracerebroventricular administration, systemic (intravenous) infusion of the same dose of PACAP38 caused significantly smaller hyperthermia, indicating a central site of action. We then investigated the thermoregulatory phenotype of mice lacking the Pacap gene (Pacap −/−). Freely moving Pacap −/− mice had higher locomotor activity throughout the day and elevated deep T b during the light phase. When the Pacap −/− mice were loosely restrained, their metabolic rate and T b were lower compared to their wild-type littermates. We conclude that PACAP38 causes hyperthermia via activation of the autonomic cold-defense thermoeffectors through central targets. Pacap −/− mice express hyperkinesis, which is presumably a compensatory mechanism, because under restrained conditions, these mice are hypometabolic and hypothermic compared to controls.

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Acknowledgments

This research has been supported by the Hungarian Scientific Research Fund (grants PD 105532, PD 100706, and K 104984), the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00785/12/5), the TAMOP (grants 4.2.2.A-11/1/KONV-2012-0024 and 4.2.4.A/2-11-1-2012-0001), the Arimura Foundation, the PTE-MTA “Lendulet” Program, and the Hungarian Brain Research Program (grant KTIA_13_NAP-A-III/5).

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Authors and Affiliations

  1. Department of Anatomy PTE-MTA “Lendulet” PACAP Research Team, Medical School, University of Pecs, Pecs, Hungary

    Eszter Banki, Balazs Gaszner, Andras Czett, Andrea Tamas & Dora Reglodi

  2. Department of Pathophysiology and Gerontology, Medical School, University of Pecs, 12 Szigeti Str, Pecs, Hungary, H7624

    Eszter Pakai, Csaba Zsiboras, Paras Rahul Parkash Bhuddi & Andras Garami

  3. Graduate School of Pharmacological Sciences, Osaka University, Osaka, Japan

    Hitoshi Hashimoto

  4. Department of Medical Chemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary

    Gabor Toth

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  1. Eszter Banki
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  2. Eszter Pakai
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  3. Balazs Gaszner
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  4. Csaba Zsiboras
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  9. Andrea Tamas
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Correspondence to Andras Garami.

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Eszter Banki and Eszter Pakai contributed equally to this work.

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Banki, E., Pakai, E., Gaszner, B. et al. Characterization of the Thermoregulatory Response to Pituitary Adenylate Cyclase-Activating Polypeptide in Rodents. J Mol Neurosci 54, 543–554 (2014). https://doi.org/10.1007/s12031-014-0361-0

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