Article
Multidisciplinary Sciences
Han-Tao Li, Dane C. Donegan, Daria Peleg-Raibstein, Denis Burdakov
Summary: This study explores a deep brain stimulation (DBS) strategy for modulating anxiety symptoms by targeting the lateral hypothalamus (LH). The researchers identify a DBS waveform that inhibits anxiety-related neural activity and suppresses anxiety behaviors in mouse models without any noticeable side effects. These findings suggest that acute hypothalamic DBS could be a potential strategy for managing treatment-resistant anxiety disorders.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Clinical Neurology
Silvia Melzi, Anne-Laure Morel, Celine Scote-Blachon, Roland Liblau, Yves Dauvilliers, Christelle Peyron
Summary: The study found that in mouse models, the expression levels of histamine and noradrenaline, two wake-promoting systems, are not regulated by orexin levels, whether orexin deficiency is constitutive or induced at adult age. It also showed that there was no recruitment of histamine by local neuroinflammation. Further research is needed to define the role of histamine in the pathophysiology of narcolepsy type 1.
Article
Neurosciences
Carlos Carrera-Canas, Isabel de Andres, Marta Callejo, Miguel Garzon
Summary: The hypothalamic hypocretinergic/orexinergic system plays a role in various physiological processes, and dysfunction of this system leads to narcolepsy. This study used the drug suvorexant to block Hcrt/Ox transmission in rats and observed changes in body weight, cerebrospinal fluid levels of Hcrt1/OxA, and levels of Hcrt/Ox receptors in the hypothalamus. The results showed that blocking Hcrt/Ox transmission caused weight gain, decreased Hcrt1/OxA levels, and overexpression of Hcrt/OxR1 in the hypothalamus.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Cardiac & Cardiovascular Systems
Rajna Knez, Milan Niksic, Elmir Omerovic
Summary: Takotsubo syndrome (TTS) is an acute heart failure syndrome with unclear pathophysiological mechanisms. During the COVID-19 pandemic, an increased incidence of TTS has been reported. This study proposes a possible connection between orexin-system dysfunction and TTS, based on the observation of COVID-19 symptoms. The research suggests that orexin signaling dynamics may influence cardiac contractility and contribute to TTS pathophysiology.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Neurosciences
Mathilde C. C. Guillaumin, Denis Burdakov
Summary: Most studies of neural circuit connectivity focus on millisecond-scale interactions mediated by classical fast transmitters, while overlooking the slow-acting peptide transmitters in the brain. Neuropeptides can efficiently implement sustained neural circuit connectivity and have unique advantages for efficient neuronal processing and feedback control of consciousness. The sustained actions of neuropeptides on neuronal membrane potential may enable core brain functions and the creation of lasting permissive signals for context-dependent information routing and plasticity.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Neurosciences
Mayda Rivas, Diego Serantes, Florencia Pena, Joaquin Gonzalez, Annabel Ferreira, Pablo Torterolo, Luciana Benedetto
Summary: HCRT, also known as orexins, are synthesized by neurons located in the postero-lateral hypothalamus and are associated with a wide range of physiological functions. In lactating rats, HCRT in the mPOA promotes wakefulness while a dual orexin receptor antagonist (DORA) promotes sleep and nursing behaviors.
Article
Clinical Neurology
Ling Shan, Rawien Balesar, Dick F. Swaab, Gert Jan Lammers, Rolf Fronczek
Summary: The study discovered that narcolepsy type 1 leads to the loss of hypocretin neurons in the hypothalamus, while sparing other neuronal populations. This selective decrease in hypocretin neurons provides novel targets for diagnostics and therapeutic interventions.
ANNALS OF NEUROLOGY
(2022)
Article
Pharmacology & Pharmacy
Tzu-Ling Li, Yen-Hsien Lee, Feng-Hsu Wu, Ling-Ling Hwang
Summary: Orexin-A directly excites over half of DMH neurons, including those innervating the RVLM, through decreasing K+ conductance, activating NCX, and/or increasing NSCC.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Neurosciences
Dane Donegan, Christoph M. Kanzler, Julia Buescher, Paulius Viskaitis, Ed F. Bracey, Olivier Lambercy, Denis Burdakov
Summary: Skilled arm movements require adaptation based on sensory errors, and studies in mice show that forelimb motor adaptation is regulated by the hypothalamic orexin/hypocretin neurons (HONs). By studying goal-oriented mouse-robot interactions, distinct HON signals were found during forelimb movements and motor adaptation. Temporally-delimited optosilencing of these movement-associated HON signals impaired sensory error-based motor adaptation.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Psychiatry
Jing Lu, Man-Li Huang, Jin-Hui Li, Kang-Yu Jin, Hai-Mei Li, Ting-Ting Mou, Rolf Fronczek, Jin-Feng Duan, Wei-Juan Xu, Dick Swaab, Ai-Min Bao
Summary: Research indicates decreased central hypocretin neurotransmission in schizophrenia patients, especially females. Plasma hypocretin-1 levels were significantly lower in schizophrenia patients, with female patients showing a more significant decrease. Hypothalamic hypocretin-1 ir also decreased in schizophrenia patients, primarily in females, while male patients showed changes in Hcrt-R mRNA expression.
SCHIZOPHRENIA BULLETIN
(2021)
Article
Biology
Elisa M. Fonseca, Tara A. Janes, Stephanie Fournier, Luciane H. Gargaglioni, Richard Kinkead
Summary: The study found that in pre-metamorphic bullfrog tadpoles, OX(1)Rs facilitate the expression of the motor command associated with air breathing, and different respiratory stimuli can have varying effects on respiratory motor output.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Daria Peleg-Raibstein, Denis Burdakov
Summary: Hypothalamic neurons producing orexins/hypocretins have broad axonal projections throughout the brain, and are activated not only by nutrient depletion but also by diverse sensory stimuli signaling stress. This unified theory suggests that HON activity may represent a cumulative response to stress, leading to various stress-counteracting behaviors.
Article
Endocrinology & Metabolism
Alba Clara Fernandez-Rilo, Nicola Forte, Letizia Palomba, Lea Tunisi, Fabiana Piscitelli, Roberta Imperatore, Alfonso Di Costanzo, Vincenzo Di Marzo, Luigia Cristino
Summary: This study investigated the role of the endogenous compound 2-AGP in appetite regulation and found its correlation with orexin-A (OX-A). This finding reveals a new molecular pathway involved in energy homeostasis regulation, which could be targeted to treat obesity and related disturbances.
MOLECULAR METABOLISM
(2023)
Article
Clinical Neurology
Silvia Melzi, Vincent Prevot, Christelle Peyron
Summary: Narcolepsy type 1 (NT1) is a rare neurological sleep disorder associated with autoimmune origins and neuroinflammation. This review suggests that the occurrence of precocious puberty in NT1 may be due to hypothalamic dysfunction caused by neuroinflammation, rather than the lack of orexin/hypocretin. Replacement therapy with orexin/hypocretin may be a potential treatment for precocious puberty in NT1 patients.
SLEEP MEDICINE REVIEWS
(2022)
Article
Psychology, Biological
Nadine Faesel, Michael Koch, Markus Fendt
Summary: Binge eating disorder is a debilitating disease associated with excessive food consumption and psychiatric comorbidities. This study investigates the role of the orexin neuropeptide system in binge-like eating, finding a sexual dimorphism in its effects on weight, hypophagia, stress levels, and anxiety.
PHYSIOLOGY & BEHAVIOR
(2023)
Article
Chemistry, Medicinal
Curt A. Dvorak, Dale A. Rudolph, Diane Nepomuceno, Lisa Dvorak, Brian Lord, Ian Fraser, Pascal Bonaventure, Timothy Lovenberg, Nicholas I. Carruthers
Summary: A novel dual 5-HT7/5-HT2 receptor antagonist, 3-(4-Fluorophenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene (4j), showed high affinity for both receptors with potential therapeutic efficacy in in vivo models for central 5-HT7 and 5-HT2A activity.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Immunology
Susana S. Correia, Guang Liu, Sarah Jacobson, Sylvie G. Bernier, Jenny V. Tobin, Chad D. Schwartzkopf, Emily Atwater, Elisabeth Lonie, Sam Rivers, Andrew Carvalho, Peter Germano, Kim Tang, Rajesh R. Iyengar, Mark G. Currie, John R. Hadcock, Christopher J. Winrow, Juli E. Jones
Summary: CYR119, a CNS-penetrant sGC stimulator, attenuates neuroinflammation by increasing cGMP production and shows neuroprotective effects in vivo models.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Pharmacology & Pharmacy
Susana S. Correia, Rajesh R. Iyengar, Peter Germano, Kim Tang, Sylvie G. Bernier, Chad D. Schwartzkopf, Jenny Tobin, Thomas W. -H. Lee, Guang Liu, Sarah Jacobson, Andrew Carvalho, Glen R. Rennie, Joon Jung, Paul A. Renhowe, Elisabeth Lonie, Christopher J. Winrow, John R. Hadcock, Juli E. Jones, Mark G. Currie
Summary: Effective treatments for neurodegenerative diseases are urgently needed as the global population ages. CY6463, a brain-penetrant sGC stimulator, has shown promise in preclinical models by improving neuronal activity, mediating neuroprotection, and enhancing cognitive performance.
FRONTIERS IN PHARMACOLOGY
(2021)
Letter
Genetics & Heredity
Katy Phelan, Luigi Boccuto, Craig M. Powell, Tobias M. Boeckers, Conny van Ravenswaaij-Arts, R. Curtis Rogers, Carlo Sala, Chiara Verpelli, Audrey Thurm, William E. Bennett, Christopher J. Winrow, Sheldon R. Garrison, Roberto Toro, Thomas Bourgeron
Summary: Phelan-McDermid syndrome, initially known as 22q13 deletion syndrome, is now recognized to be associated with SHANK3 gene. To reduce confusion, a simple classification system has been proposed, dividing PMS into PMS-SHANK3 related and PMS-SHANK3 unrelated cases.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Pharmacology & Pharmacy
Anthony W. Harrington, Changlu Liu, Naomi Phillips, Diane Nepomuceno, Chester Kuei, Joseph Chang, Weixuan Chen, Steven W. Sutton, Daniel O'Malley, Ly Pham, Xiang Yao, Siquan Sun, Pascal Bonaventure
Summary: The study suggests that oxysterols, including 24S-HC, could be physiological activators for GPR17, regulating oligodendrocyte progenitor cell differentiation and myelination through receptor activation.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Meeting Abstract
Medicine, Research & Experimental
Emmanuel S. Buys, Susana S. Correia, Guang Liu, Joon Jung, John R. Hadcock, Peter Germano, Christopher J. Winrow, Juli E. Jones
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Meeting Abstract
Medicine, Research & Experimental
Christopher J. Winrow
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Meeting Abstract
Neurosciences
Benjamin Throesch, Michelle Wennerholm, Pascal Bonaventure, Grace Woodruff
NEUROPSYCHOPHARMACOLOGY
(2022)
Meeting Abstract
Neurosciences
Stacey Versavel, Rachel Gurrell, Ih Chang, Ann Dandurand, Sridhar Duvvuri, Amy Giugliano, Gina Pastino, Theresa Pham, Gabriel Jacobs, Koshar Safai Pour, Rob Zuiker, Raymond Sanchez, John Renger
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Medicine, General & Internal
John H. Krystal, John M. Kane, Christoph U. Correll, David P. Walling, Matthew Leoni, Sridhar Duvvuri, Shrinal Patel, Ih Chang, Philip Iredale, Lillian Frohlich, Stacey Versavel, Pamela Perry, Raymond Sanchez, John Renger
Summary: The trial involved two parts with a total of 167 schizophrenia patients. The results showed that emraclidine once-daily treatment had good safety and tolerability, demonstrating potential for further investigation as a treatment for schizophrenia.
Meeting Abstract
Neurosciences
Benjamin Throesch, Michelle Wennerholm, Pascal Bonaven-Ture, Grace Woodruff
NEUROPSYCHOPHARMACOLOGY
(2021)
Meeting Abstract
Neurosciences
Sridhar Duvvuri, Philip Iredale, Matthew Leoni, Vasily Belov, Nicolas Guehl, Sung-Hyun Moon, Maeva Dhaynaut, Peter Rice, Daniel Yokell, Georges El Fakhri, Marc Normandin, John Renger
NEUROPSYCHOPHARMACOLOGY
(2021)
Meeting Abstract
Neurosciences
John Krystal, John Kane, Christoph Correll, David Walling, Matthew Leoni, Sridhar Duvvuri, Ih Chang, Philip Iredale, Stacey Versavel, Lillian Frohlich, Shrinal PatelPamela Perry, Raymond Sanchez, John Renger
NEUROPSYCHOPHARMACOLOGY
(2021)
Meeting Abstract
Endocrinology & Metabolism
Vasily Belov, Nicolas J. Guehl, Sridhar Duvvuri, Philip Iredale, Sung-Hyun Moon, Maeva Dhaynaut, Peter A. Rice, Daniel L. Yokell, John Renger, Georges El Fakhri, Marc D. Normandin
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Medicine, Research & Experimental
Rahul Sasane, Amy Bartels, Michelle Field, Maria I. Sierra, Sridhar Duvvuri, David L. Gray, Sokhom S. Pin, John J. Renger, David J. Stone
Summary: The study found that tamsulosin users had a significantly higher incidence of Parkinson's disease compared to terazosin/alfuzosin/doxazosin users and matched controls. There was no significant difference in Parkinson's disease risk between terazosin/alfuzosin/doxazosin users and matched controls. These results suggest that tamsulosin may exacerbate Parkinson's disease progression.
JOURNAL OF CLINICAL INVESTIGATION
(2021)