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      Thermoregulation under pressure: a role for orexin neurons

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          Abstract

          In the past, studies on stress responses and sleep/wake regulation were performed separately. The discovery of orexin (hypocretin) in 1998, however, dramatically changed the course of research and new findings regarding its role in these complex processes provided a better insight into their interactions and intricacies. Orexin-containing neuronal activity has been found to be minimal during sleep. It increases during the waking period and further increases during the active waking period, which includes stress responses and exploratory behaviors. Autonomic regulation of the body, which includes body temperature, blood flow, and ventilation, is also activated along with the change in vigilance states. Our recent findings suggest that orexin neurons act as a conductor of orchestration for vigilance states, behaviors, and autonomic functions. Body temperature regulation by orexin neurons seems to be mediated by one of its cotransmitters while cardiovascular and respiratory regulation are mediated by orexin itself.

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          Most cited references103

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          Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.

          The hypothalamus plays a central role in the integrated control of feeding and energy homeostasis. We have identified two novel neuropeptides, both derived from the same precursor by proteolytic processing, that bind and activate two closely related (previously) orphan G protein-coupled receptors. These peptides, termed orexin-A and -B, have no significant structural similarities to known families of regulatory peptides. prepro-orexin mRNA and immunoreactive orexin-A are localized in neurons within and around the lateral and posterior hypothalamus in the adult rat brain. When administered centrally to rats, these peptides stimulate food consumption. prepro-orexin mRNA level is up-regulated upon fasting, suggesting a physiological role for the peptides as mediators in the central feedback mechanism that regulates feeding behavior.
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            The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity.

            We describe a hypothalamus-specific mRNA that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin. The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas. The fibers of these neurons are widespread throughout the posterior hypothalamus and project to multiple targets in other areas, including brainstem and thalamus. Hcrt immunoreactivity is associated with large granular vesicles at synapses. One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters.
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              Reduced number of hypocretin neurons in human narcolepsy.

              Murine and canine narcolepsy can be caused by mutations of the hypocretin (Hcrt) (orexin) precursor or Hcrt receptor genes. In contrast to these animal models, most human narcolepsy is not familial, is discordant in identical twins, and has not been linked to mutations of the Hcrt system. Thus, the cause of human narcolepsy remains unknown. Here we show that human narcoleptics have an 85%-95% reduction in the number of Hcrt neurons. Melanin-concentrating hormone (MCH) neurons, which are intermixed with Hcrt cells in the normal brain, are not reduced in number, indicating that cell loss is relatively specific for Hcrt neurons. The presence of gliosis in the hypocretin cell region is consistent with a degenerative process being the cause of the Hcrt cell loss in narcolepsy.
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                Author and article information

                Journal
                Temperature (Austin)
                Temperature (Austin)
                KTMP
                Temperature: Multidisciplinary Biomedical Journal
                Taylor & Francis
                2332-8940
                2332-8959
                Jul-Sep 2015
                15 July 2015
                15 July 2015
                : 2
                : 3 , Japanese Thermal Physiology; Guest Editor: Osamu Shido, MD, PhD
                : 379-391
                Affiliations
                Department of Physiology; Kagoshima University Graduate School of Medical and Dental Sciences ; Kagoshima, Japan
                Author notes
                [* ]Correspondence to: Tomoyuki Kuwaki; Email: kuwaki@ 123456m3.kufm.kagoshima-u.ac.jp ; URL: www.famelab.gr
                Article
                1066921
                10.1080/23328940.2015.1066921
                4843912
                27227052
                77e1b905-e7d9-4242-90bb-db65bc3fb620
                © 2015 The Author(s). Published with license by Taylor & Francis Group, LLC

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

                History
                : 22 May 2015
                : 20 June 2015
                : 22 June 2015
                Page count
                Figures: 10, Tables: 0, References: 112, Pages: 13
                Categories
                Review

                autonomic nervous system,breathing regulation,cardiovascular control,fight-or-flight,pain,stress,sleep,thermoregulation

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