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      Human hypocretin and melanin concentrating hormone levels are linked to emotion and social interaction

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          Abstract

          The neurochemical changes underlying human emotions and social behavior are largely unknown. Here we report on the changes in the levels of two hypothalamic neuropeptides, hypocretin-1 (Hcrt-1) and melanin concentrating hormone (MCH), measured in the human amygdala. We show that Hcrt-1 levels are maximal during positive emotion, social interaction, and anger, behaviors that induce cataplexy in human narcoleptics. In contrast, MCH levels are minimal during social interaction, but are increased after eating. Both peptides are at minimal levels during periods of postoperative pain despite high levels of arousal. MCH levels increase at sleep onset, consistent with a role in sleep induction, whereas Hcrt-1 levels increase at wake onset, consistent with a role in wake induction. Levels of these two peptides in humans are not simply linked to arousal, but rather to specific emotions and state transitions. Other arousal systems may be similarly emotionally specialized.

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          Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior

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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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                Author and article information

                Journal
                101528555
                37539
                Nat Commun
                Nat Commun
                Nature communications
                2041-1723
                8 February 2013
                5 March 2013
                05 September 2013
                : 4
                : 1547
                Affiliations
                [1 ]Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Los Angeles, CA 90095
                [2 ]Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland 21205
                [3 ]Department of Neurosurgery, University of California at Los Angeles, Los Angeles, CA 90095
                [4 ]Brain Research Institute, University of California at Los Angeles, Los Angeles, CA 90095
                [5 ]Department of Neurology, University of California at Los Angeles, Los Angeles, CA 90095
                [6 ]Dept of Biomedical Engineering, School of Science and Engineering, Reykjavik University, Reykjavik, Iceland
                [7 ]Neurobiology Research, Veterans Administration Greater Los Angeles Healthcare System, 16111 Plummer St., North Hills, CA 91343
                Author notes
                []Correspondence and requests for materials should be addressed to J.M.S. ( JSiegel@ 123456ucla.edu )
                Article
                NIHMS434503
                10.1038/ncomms2461
                3595130
                23462990
                43cc6d12-4a18-4bdd-be15-1d1e11c79e8e
                History
                Funding
                Funded by: National Institute of Neurological Disorders and Stroke : NINDS
                Award ID: R01 NS014610 || NS
                Funded by: National Institute of Mental Health : NIMH
                Award ID: R01 MH064109 || MH
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