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

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 thermoregu...

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Bibliographic Details
Published in:	Journal of molecular neuroscience Vol. 54; no. 3; pp. 543 - 554
Main Authors:	Banki, Eszter, Pakai, Eszter, Gaszner, Balazs, Zsiboras, Csaba, Czett, Andras, Bhuddi, Paras Rahul Parkash, Hashimoto, Hitoshi, Toth, Gabor, Tamas, Andrea, Reglodi, Dora, Garami, Andras
Format:	Journal Article
Language:	English
Published:	Boston Springer US 01-11-2014 Springer Nature B.V
Subjects:	Amino acids Animals Biomedical and Life Sciences Biomedicine Body temperature Cell Biology Female Fever Fever - genetics Fever - metabolism Hyperthermia Hypothalamus Male Medical research Metabolism Mice Nervous system Neurochemistry Neurology Neurosciences Physiology Pituitary Adenylate Cyclase-Activating Polypeptide - genetics Pituitary Adenylate Cyclase-Activating Polypeptide - metabolism Pituitary Adenylate Cyclase-Activating Polypeptide - pharmacology Polypeptides Proteomics Rats Rats, Wistar Thermogenesis Thermogenesis - drug effects Hungary Thermoregulation PACAP Hyperthermia Locomotor activity Autonomic thermoeffectors
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0895-8696 1559-1166
DOI:	10.1007/s12031-014-0361-0