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
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
Anatomy & Morphology
Eliandra N. da Silva, Jose de Anchieta C. Horta-Junior, Luciane H. Gargaglioni, Mirela B. Dias
Summary: The orexinergic neurons in different nuclei show distinct activation by CO2 levels, suggesting a differential role of hypothalamic nuclei in central chemosensitivity.
BRAIN STRUCTURE & FUNCTION
(2022)
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)
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
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)
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
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
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)
Review
Medicine, General & Internal
Balazs Csoma, Maria Rosaria Vulpi, Silvano Dragonieri, Andrew Bentley, Timothy Felton, Zsofia Lazar, Andras Bikov
Summary: Chronic obstructive pulmonary disease (COPD) leads to chronic hypercapnia, which negatively affects multiple aspects of health, including the lungs and cardiovascular system. Noninvasive ventilation is an effective technique for removing carbon dioxide and treating chronic hypercapnia. However, there are controversies and further research needed in this field.
JOURNAL OF CLINICAL MEDICINE
(2022)
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
Respiratory System
Matthias Roetting, Katharina Kriegsmann, Markus Polke, Nilab Polke, Konstantina Kontogianni, Ralf Eberhardt, Felix J. F. Herth, Daniela Gompelmann
Summary: This retrospective analysis examined the efficacy of endoscopic valve treatment in COPD patients with hypercapnia. The results showed significant improvements in lung function and 6-minute walk test, as well as a significant reduction in pCO(2) levels at 3 and 6 months following valve implantation. 40% of the patients achieved normal pCO(2) values after the intervention. These findings suggest that valve treatment can be effective in improving respiratory outcomes in COPD patients with hypercapnia.
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
Immunology
Francesca Spiga, Zidong Zhao, Stafford L. Lightman
BRAIN BEHAVIOR AND IMMUNITY
(2020)
Letter
Endocrinology & Metabolism
Ben Gibbison, Daniel M. Keenan, Ferdinand Roelfsema, Jon Evans, Kirsty Phillips, Chris A. Rogers, Gianni D. Angelini, Stafford L. Lightman
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2020)
Article
Endocrinology & Metabolism
Lorna I. F. Smith, Zidong Zhao, Jamie Walker, Stafford Lightman, Francesca Spiga
Summary: This study investigated the activation and expression of CRTC isoforms in rat adrenal glands under different stress conditions. The results showed that CRTC2 and CRTC3 play important roles in the transcriptional regulation of StAR, with their activation and nuclear localization associated with changes in plasma ACTH levels. Both isoforms were found to bind to the Star promoter, with CRTC3 binding dynamics corresponding to changes in nuclear protein levels. While little variation was observed in CRTC isoform expression over a 24-hour period, long-term down-regulation was observed following endotoxic stress.
JOURNAL OF NEUROENDOCRINOLOGY
(2021)
Article
Cell Biology
Daniel P. Fudulu, George Horn, Georgina Hazell, Anne-Marie Lefrancois-Martinez, Antoine Martinez, Gianni D. Angelini, Stafford L. Lightman, Francesca Spiga
Summary: The hypothalamic-pituitary-adrenal axis is activated during periods of stress, such as critical illness, to re-establish homeostasis. Inflammation of the adrenal glands during critical illness may contribute to immune-adrenal communication and modulation of cortisol secretion. Studies show that inflammatory stimuli, like LPS, can affect the expression of adrenal steroidogenic enzymes and genes, with potential implications for clinical practice.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Genetics & Heredity
Benjamin P. Flynn, Matthew T. Birnie, Yvonne M. Kershaw, Audrys G. Pauza, Sohyoung Kim, Songjoon Baek, Mark F. Rogers, Alex R. Paterson, Diana A. Stavreva, David Murphy, Gordon L. Hager, Stafford L. Lightman, Becky L. Conway-Campbell
Summary: The study demonstrates that pulsatile and constant corticosterone replacement in rats can induce different binding patterns of glucocorticoid receptor at genomic sites in the liver, leading to varied transcriptional responses and effects on RNA polymerase II occupancy. These differences result in distinct regulation of gene targets and pathways related to metabolism and inflammation, highlighting the potential functional role of dysregulated glucocorticoid rhythms in metabolic dysfunction.
Article
Pharmacology & Pharmacy
Ioannis G. Violaris, Konstantinos Kalafatakis, Eder Zavala, Ioannis G. Tsoulos, Theodoros Lampros, Stafford L. Lightman, Markos G. Tsipouras, Nikolaos Giannakeas, Alexandros Tzallas, Georgina M. Russell
Summary: A pharmacokinetic model was developed to predict plasma cortisol levels at any point of the day from a limited number of measurements with high accuracy. The model accurately predicted levels with only four measurements and successfully supported clinical trials involving subcutaneous HC delivery in patients with reduced endogenous capacity to synthesize GCs.
Meeting Abstract
Clinical Neurology
J. Thakrar, K. Kalafatakis, J. Brooks, J. King, G. M. Russell, M. Munafo, I. Penton-Voak, A. Wilson, N. J. Thai, R. Moran, S. Quadflieg, S. L. Lightman
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Endocrinology & Metabolism
Francesca Spiga, Michael A. Lawton, Stafford L. Lightman, George Davey Smith, Yoav Ben-Shlomo
Summary: The study found differences in the association between social class and cortisol in an aging male population, with lower social class being linked to slower recovery of cortisol levels after exposure to stress.
PSYCHONEUROENDOCRINOLOGY
(2022)
Letter
Endocrinology & Metabolism
Kyriakie Sarafoglou, Oppong Yaw Addo, James S. Hodges, Richard C. Brundage, Stafford L. Lightman, Peter C. Hindmarsh, Bradley S. Miller
HORMONE RESEARCH IN PAEDIATRICS
(2022)
Article
Endocrinology & Metabolism
Matthew T. Birnie, Alen Eapen, Yvonne M. Kershaw, David Lodge, Graham L. Collingridge, Becky L. Conway-Campbell, Stafford L. Lightman
Summary: More than 50% of depressed patients exhibit hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Ketamine, a rapid-acting antidepressant, has a significant impact on HPA axis function. The timing of ketamine administration may be crucial for its glucocorticoid-mediated action in depression.
JOURNAL OF NEUROENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Geffen Lass, Xiao Feng Li, Margaritis Voliotis, Ellen Wall, Ross A. de Burgh, Deyana Ivanova, Caitlin McIntyre, Xian-Hua Lin, William H. Colledge, Stafford L. Lightman, Krasimira Tsaneva-Atanasova, Kevin T. O'Byrne
Summary: Research has shown that kisspeptin neurons in certain brain regions can significantly modulate the kisspeptin population in the hypothalamus, increasing luteinising hormone pulse frequency. Experimental studies have demonstrated that neurotransmission of both GABA and glutamate is crucial for this regulatory function.
JOURNAL OF NEUROENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Felicity E. Stubbs, Benjamin P. Flynn, Caroline A. Rivers, Matthew T. Birnie, Andrew Herman, Erin E. Swinstead, Songjoon Baek, Hai Fang, Jillian Temple, Jason S. Carroll, Gordon L. Hager, Stafford L. Lightman, Becky L. Conway-Campbell
Summary: ARID1a knockdown leads to decreased chromatin accessibility and affects a subset of glucocorticoid binding sites. Knockdown of ARID1a specifically affects gene expression related to cell cycle regulation and DNA repair, while the majority of glucocorticoid-regulated genes are unaffected. Using liquid chromatography-mass spectrometry, a chromatin-associated protein complex involving ARID1a and DNA damage repair proteins is identified, and its loss impairs DNA damage repair mechanisms.
Article
Neurosciences
Philippe C. Habets, Konstantinos Kalafatakis, Oleh Dzyubachyk, Steven J. A. van der Werff, Arlin Keo, Jamini Thakrar, Ahmed Mahfouz, Alberto M. Pereira, Georgina M. Russell, Stafford L. Lightman, Onno C. Meijer
Summary: Recent evidence suggests that the ultradian cortisol pulsatility is crucial for normal emotional response in humans. This study investigates the anatomical and cell type signature of brain regions sensitive to a loss of ultradian rhythmicity in emotional processing. The findings highlight the importance of GABAergic function and specific genes in cortical brain areas for emotional processing response.
NEUROBIOLOGY OF STRESS
(2023)
Article
Biology
Mitsuhiro Yoshimura, Benjamin P. Flynn, Yvonne M. Kershaw, Zidong Zhao, Yoichi Ueta, Stafford L. Lightman, Becky L. Conway-Campbell
Summary: This study demonstrates how the timing of feeding behavior becomes disordered when glucocorticoid rhythms are dissociated from lighting cues. The dysregulated timing of neuropeptide gene expression is associated with this altered feeding pattern.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Daniel Galvis, Eder Zavala, Jamie J. Walker, Thomas Upton, Stafford L. Lightman, Gianni D. Angelini, Jon Evans, Chris A. Rogers, Kirsty Phillips, Ben Gibbison
Summary: Major surgery and critical illness can cause a potentially life-threatening systemic inflammatory response. The hypothalamic-pituitary-adrenal (HPA) axis plays a crucial role in counterbalancing this inflammation through changes in ACTH and cortisol. By studying patients undergoing cardiac surgery, researchers have identified three phenotypes of HPA axis response, each with different physiological mechanisms.
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2022)