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Neuropeptide Regulation of Ion Channels and Food Intake
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Orexin/hypocretin is another orexigenic neuropeptide that is produced and released by neurons located in the lateral hypothalamus. Despite the restricted expression of orexin cell body within the hypothalamus, orexin projections are found in a wide range of brain areas involved in feeding and arousal. The lateral hypothalamus synthesizes and releases orexin-A (or hypocretin-1) and orexin-B (or hypocretin-2), two structurally analogous neuropeptides, to exert functional modulation of postsynaptic neurons expressed with orexin receptors (OX1R and OX2R). In addition to orexin, orexin neurons also release dynorphin from the same synaptic vesicles which lead to a complex effect on the postsynaptic neurons (Muschamp et al. 2014; Chou et al. 2001).
Sleep–Wake Disorders
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Margaret Kay-Stacey, Eunice Torres-Rivera, Phyllis C. Zee
Ascending reticular activating system: wakefulness (Figure 28.10; Table 28.1). Location: brainstem, lateral/posterior hypothalamus, basal forebrain.The orexin- (also known as hypocretin) secreting neurons are key to maintenance of wakefulness. (Figure 28.11) These neurons have wide-ranging activating projections to the wake promoting brain, and inhibitory to sleep promoting regions, such as the ventrolateral preoptic (VLPO) nucleus (see below).
Sedative and Hypnotic Drugs
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Arup Kumar Misra, Pramod Kumar Sharma
Zolpidem, eszopiclone, and zaleplon are collectively known as “Z-drugs” though they have the same mechanism of action as benzodiazepines but they are structurally unrelated (Gregory, 2016). Ramelteon and tasimelteon are the melatonin receptor agonists which are approved by US FDA as newer hypnotics indicated for non-24-h sleep–wake disorders (Laudon, 2014). An orexin receptor antagonist, suvorexant was introduced in the market in August 2014 and is indicated to improve sleep duration. Buspirone is a slow-onset anxiolytic agent differing from the conventional sedative–hypnotics in their mechanism of action (Mendelson, 1990).
Irreversible hippocampal changes induced by high fructose diet in rats
Published in Nutritional Neuroscience, 2022
Juan Fierros-Campuzano, Paola Ballesteros-Zebadúa, Joaquín Manjarrez-Marmolejo, Penélope Aguilera, Mónica Méndez-Diaz, Oscar Prospero-García, Javier Franco-Pérez
The rats were euthanized with sodium pentobarbital (200 mg/kg, intraperitoneal) (Pisa, Mexico) and immediately decapitated; the hippocampus, prefrontal cortex, and hypothalamus were quickly dissected. Brain tissue was immersed in lysis buffer constituted by guanidine/Tris HCl (8.2 M/82 mM) in PBS, pH 8.0, and protease inhibitor cocktail (1% v/v) (Sigma-Aldrich, USA) and homogenized with an ultrasonic processor (Sonics, USA). The samples were centrifuged at 10,000 x g for 10 min at 4 °C; the supernatants were separated and stored at −20 °C. The protein concentration in each sample was determined using the bicinchoninic acid (BCA) (Sigma Aldrich, USA) method. The quantitative detection of orexin-A was carried out using a commercial ELISA kit (MBS264436, MyBioSource, USA). The protocol was followed strictly according to the manufacturer’s instructions. The minimum detectable concentration of orexin-A was 15.6 pg/ml. The intra-assay coefficient of variation was 8% and inter-assay 12%. After stopping the chromogenic reaction, the absorbance was measured with an ELISA microplate reader (ChroMate 4300, Awareness Technology Inc, USA) at 450 nm. Finally, the results were correlated with the protein concentration, and therefore the orexin-A content of each sample was expressed as pg/mg of total protein [21].
Improvement in fatigue and sleep measures with the dual orexin receptor antagonist lemborexant in adults with insomnia disorder
Published in Postgraduate Medicine, 2022
Craig Chepke, Rakesh Jain, Russell Rosenberg, Margaret Moline, Jane Yardley, Kate Pinner, Dinesh Kumar, Carlos Perdomo, Gleb Filippov, Norman Atkins, Manoj Malhotra
A number of nonpharmacologic and pharmacologic treatment options have been explored for the treatment of fatigue [5,14,15]; however, additional options are needed that may target the mechanism(s) associated with both fatigue symptoms and the comorbid condition. Although the exact pathophysiology of fatigue is not well understood, daytime fatigue related to insomnia may have a neurophysiologic explanation. Reduced metabolic activity in the prefrontal cortex resulting from insufficient sleep, as observed by functional neuroimaging, has been linked to daytime fatigue [16]. Other recent research points to altered orexin signaling as a potential mechanism for fatigue. Orexins are involved in promoting wakefulness during the sleep-wake cycle and are believed to play a key role in reward systems and energy homeostasis [17,18].
Persistent effects of the orexin-1 receptor antagonist SB-334867 on naloxone precipitated morphine withdrawal symptoms and nociceptive behaviors in morphine dependent rats
Published in International Journal of Neuroscience, 2021
Masoumeh Kourosh-Arami, Mohammad-Taghi Joghataei, Alireza Komaki, Masoumeh Gholami, Zohreh Najafi, Mostafa Lavaie
Orexins are neurotransmitters with an important role in drug addiction [1–3]. Orexin A is a well-known peptide in the lateral hypothalamus (LH). It is involved in feeding, wake cycle [4,5], and reward-related processes, including drug abuse and addiction [4–14]. Orexin neuropeptides activate OXR1 and orexin type 2 (OXR2) receptors, which are G-protein coupled receptors [15]. OXR1 has a higher affinity to orexin-A than orexin-B, while OXR2 has the same affinity for both peptides [15]. In one-week old animals, only a small subset of neurons in the LH are orexin-A positive [16]. Based on previous studies, translation of orexin mRNA can be detected at very low levels on the day of birth, followed by a rise to the maximum at PND20 [17]. Furthermore, glucosensitivity [18] of LH neurons and their response to sensory afferents [19] mature during PND0 to 3. Therefore, orexin might play an important role in the response and reaction of LH during development [17].