Review
Clinical Neurology
Ryan K. Tisdale, Akihiro Yamanaka, Thomas S. Kilduff
Summary: Animal models have played a crucial role in investigating the etiology and phenotype of narcolepsy, revealing the relationship between the hypocretin/orexin system and narcolepsy. Additionally, these models have helped us understand the mechanisms of sleep/wake regulation.
Article
Clinical Neurology
Louise Piilgaard, Laura Rose, Camille Gylling Hviid, Kristi A. Kohlmeier, Birgitte Rahbek Kornum
Summary: This study investigated the effect of sex on NT1 symptoms and sleep-wake characteristics using NT1 mice. The findings showed that females exhibited higher behavioral state instability, more wakefulness and less sleep during the dark phase, and decreased REM sleep compared to males. The study also identified a new type of behavioral arrest called delta attacks.
Article
Clinical Neurology
Geoffroy Vellieux, Justine Frija-Masson, Anny Rouvel-Tallec, Xavier Drouot, Marie-Pia D'ortho
Summary: The case describes a male patient diagnosed with narcolepsy type 1 based on sleep and wake symptoms and various investigations. Despite receiving treatment with stimulants and anti-cataplectic drugs for several years without significant improvement, the patient experienced spontaneous remission of the disease after 15 years.
NATURE AND SCIENCE OF SLEEP
(2021)
Article
Biochemistry & Molecular Biology
Yoshimasa Koyama
Summary: The loss of orexin/hypocretin results in serious sleep disorder, narcolepsy. Cataplexy is a distinct symptom of narcolepsy, characterized by sudden muscle paralysis triggered by emotional stimuli. The involvement of monoaminergic/cholinergic systems, muscle atonia-generating systems, and emotion-related systems suggests that orexin/hypocretin modulates different components of the cataplexy-inducing circuit. This review discusses recent advances in understanding the neural mechanisms controlling cataplexy and the potential for future experimental strategies in the treatment of this disease.
Article
Neurosciences
Alissa A. Coffey, Adam A. Joyal, Akihiro Yamanaka, Thomas E. Scammell
Summary: Narcolepsy is a sleep disorder that often starts in childhood, causing episodes of paralysis during wakefulness. Experimental studies using mouse models showed that there was no significant difference in cataplexy severity and wake maintenance between early-onset and adult-onset mice, but female mice had more frequent cataplexy episodes.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Neurosciences
Haniyyah Sardar, Andrea N. Goldstein-Piekarski, William J. Giardino
Summary: Narcolepsy is a sleep disorder associated with excessive daytime sleepiness and sudden intrusion of sleep during wakefulness. Type 1 narcolepsy is believed to be caused by the loss of neurons containing the arousal neuropeptide Orexin. The amygdala, a brain region involved in emotional processing, may play a critical role in narcolepsy with cataplexy.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Pharmacology & Pharmacy
Marieke Vringer, Birgitte Rahbek Kornum
Summary: Narcolepsy type 1 and type 2 are characterized by excessive daytime sleepiness and reduced quality of life, with current treatments focused on improving daytime sleepiness and reducing cataplexy. Targeting Hcrt receptors shows promise in alleviating symptoms, but careful consideration of potential side effects is required. Immunotherapies may target the core pathophysiology of narcolepsy, but further research is needed to identify the optimal therapeutic target.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2021)
Article
Multidisciplinary Sciences
Hongli Wang, Mingrui Jia
Summary: The loss of hypocretin is considered to be the primary pathophysiological mechanism of narcolepsy. Research has shown that narcolepsy patients have lower levels of thyroid hormones, which are related to sleep quality, anxiety, and depression.
SCIENTIFIC REPORTS
(2023)
Article
Pharmacology & Pharmacy
Takashi Ishikawa, Hiroe Hara, Ayumi Kawano, Kimio Tohyama, Yuichi Kajita, Yuhei Miyanohana, Tatsuki Koike, Haruhide Kimura
Summary: The loss of orexin neurons is associated with NT1, and a new OX2R agonist called TAK-994 shows potential in promoting wakefulness and improving narcolepsy-like symptoms in mouse models.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2023)
Review
Clinical Neurology
Jari K. Gool, Eva M. van Heese, Mink S. Schinkelshoek, Aniek Remmerswaal, Gert Jan Lammers, Karin D. van Dijk, Rolf Fronczek
Summary: This study assessed the effect of opioid use on narcolepsy type 1 symptom severity through a literature review and questionnaire study. The results showed that opioids could improve narcolepsy symptom severity, with the most significant improvements seen in sleep quality and excessive daytime sleepiness.
Editorial Material
Clinical Neurology
Tomi Sarkanen, Gabriele Sved, Maria Juujarvi, Anniina Alakuijala, Markku Partinen
Summary: This article reports four cases of false positives and misdiagnosis of narcolepsy due to measurement of orexin levels using enzyme immune assay (EIA), therefore strongly discouraging the use of orexin EIA measurement in a clinical setting.
JOURNAL OF CLINICAL SLEEP MEDICINE
(2022)
Article
Clinical Neurology
Mahesh K. Kaushik, Kosuke Aritake, Yoan Cherasse, Aya Imanishi, Takashi Kanbayashi, Yoshihiro Urade, Masashi Yanagisawa
Summary: The neuropeptides orexins/hypocretins promote and stabilize wakefulness by binding to OX1R and OX2R receptors. Although the orexin receptor antagonist suvorexant is clinically approved for treating insomnia, it can potentially induce narcolepsy-like symptoms in mice under certain conditions, such as chronic administration and stress-free environment with chocolate.
Review
Neurosciences
Vishal Chavda, Bipin Chaurasia, Giuseppe E. Umana, Santino Ottavio Tomasi, Bingwei Lu, Nicola Montemurro
Summary: Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness and brief involuntary sleep episodes. The exact pathophysiology is unknown and differential diagnosis can be challenging. Treatment should be tailored to the patient's symptoms and clinical diagnosis.
Review
Clinical Neurology
Sara Katherine Pintwala, John Peever
Summary: This review discusses the symptoms, neuropathological basis, and laboratory animal models of narcolepsy. The relationship between narcolepsy and the loss of the orexin system, as well as the loss of muscle activity, is considered to be an important part of the pathogenesis of narcolepsy.
Article
Clinical Neurology
Melanie Strauss, Lucie Griffon, Maxime Elbaz, Isabelle Arnulf, Mounir Chennaoui, Damien Leger
Summary: This study examines decision-making impairments in individuals with central disorders of hypersomnolence (CDH), specifically narcolepsy type 1 (NT1). The results suggest that both NT1 and other CDH patients have decreased learning abilities to avoid losses, which is associated with alterations in vigilance. The study provides new insights into the nature of decision-making impairments in CDH and suggests the potential for minimizing these alterations by restoring adequate vigilance.
Article
Physiology
Joel C. Geerling, Minjee Kim, Carrie E. Mahoney, Stephen B. G. Abbott, Lindsay J. Agostinelli, Alastair S. Garfield, Michael J. Krashes, Bradford B. Lowell, Thomas E. Scammell
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
(2016)
Article
Neurosciences
L. L. Ferrari, L. J. Agostinelli, M. J. Krashes, B. B. Lowell, T. E. Scammell, E. Arrigoni
JOURNAL OF PHYSIOLOGY-LONDON
(2016)
Article
Neurosciences
Lindsay J. Agostinelli, Loris L. Ferrari, Carrie E. Mahoney, Takatoshi Mochizuki, Bradford B. Lowell, Elda Arrigoni, Thomas E. Scammell
JOURNAL OF COMPARATIVE NEUROLOGY
(2017)
Article
Neurosciences
Yo Oishi, Rhiannan H. Williams, Lindsay Agostinelli, Elda Arrigoni, Patrick M. Fuller, Takatoshi Mochizuki, Clifford B. Saper, Thomas E. Scammell
JOURNAL OF NEUROSCIENCE
(2013)
Article
Anatomy & Morphology
Lindsay J. Agostinelli, Joel C. Geerling, Thomas E. Scammell
BRAIN STRUCTURE & FUNCTION
(2019)
Article
Neurosciences
Lindsay J. Agostinelli, Madison R. Mix, Marco M. Hefti, Thomas E. Scammell, Alexander G. Bassuk
Summary: The study identifies a novel inhibitory neuron population LJA5 in the mouse and human brainstem. These neurons send specifically inhibitory descending projections to lamina I of the spinal cord, which transmit afferent pain, temperature, and itch information to the brain. LJA5 neurons receive inputs from sensory and stress areas, suggesting they are uniquely positioned to be activated by sensation and stress, consequently inhibiting pain and itch.
JOURNAL OF COMPARATIVE NEUROLOGY
(2021)
Article
Neurosciences
Lindsay J. Agostinelli, Alexander G. Bassuk
Summary: The study identified a novel population of GABAergic neurons called LJA5 that provide a specific inhibitory projection to lamina I of the spinal cord, reducing pain and itch. Activating these neurons could offer new treatment opportunities for chronic, refractory pain and pruritis.
JOURNAL OF COMPARATIVE NEUROLOGY
(2021)