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
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
Behavioral Sciences
Max McDermott, Akila Ram, Matthew T. Mattoon, Emmaline E. Haderlie, Megan C. Raddatz, Madi K. Thomason, Erin N. Bobeck
Summary: ProSAAS is a highly abundant protein in the brain and can be divided into smaller peptides. BigLEN, one of the peptides, acts as an endogenous ligand for the GPR171 receptor. Recent research on rodent models has shown that a small-molecule ligand for GPR171, MS15203, increases analgesic effects and reduces chronic pain. However, the potential for abuse of GPR171 has not yet been evaluated. In this study, the distribution of GPR171 and ProSAAS in the brain's reward circuit was mapped using immunohistochemistry, and it was found that GPR171 and ProSAAS are localized in several brain regions. The effects of MS15203 on neuronal activation and reward-related behavior were assessed, and the results showed that MS15203 did not increase activation of the reward circuitry or produce reward-related behavior. These findings suggest that MS15203 has minimal reward liability and support further exploration of GPR171 as a potential target for pain treatment.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2023)
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
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.
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
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
Clinical Neurology
Francois Ricordeau, Agathe Bridoux, Veronique Raverot, Laure Peter-Derex
Summary: According to the guidelines of the International Classification of Sleep Disorders, the diagnosis of narcolepsy type 1 is based on excessive daytime sleepiness plus either cataplexy and specific criteria, or a cerebrospinal fluid hypocretin-1 concentration below 110 pg/mL. However, there is ongoing debate regarding the threshold for hypocretin-1 concentration. In this case report, a patient with typical symptoms of narcolepsy type 1 had initially negative test results, but subsequent reassessment and test results confirmed the diagnosis, emphasizing the importance of reassessing patients with intermediate hypocretin-1 values.
JOURNAL OF CLINICAL SLEEP MEDICINE
(2023)
Article
Multidisciplinary Sciences
Emi Hasegawa, Ai Miyasaka, Katsuyasu Sakurai, Yoan Cherasse, Yulong Li, Takeshi Sakurai
Summary: The sleep cycle involves alternating non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. A transient increase of dopamine in the basolateral amygdala terminates NREM sleep and initiates REM sleep, playing a critical role in sleep cycle generation. This mechanism is also implicated in cataplectic attacks in narcoleptics.
Article
Neurosciences
Can Wang, Meiyu Chen, Chuan Qin, Xiaoyi Qu, Xueyong Shen, Sheng Liu
Summary: The study found that acupuncture-induced pain relief can result in a rewarding effect, and the orexin signaling in the lateral hypothalamus plays a critical role in this process.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
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)
Article
Multidisciplinary Sciences
Jie Yin, Yanyong Kang, Aaron P. McGrath, Karen Chapman, Megan Sjodt, Eiji Kimura, Atsutoshi Okabe, Tatsuki Koike, Yuhei Miyanohana, Yuji Shimizu, Rameshu Rallabandi, Peng Lian, Xiaochen Bai, Mack Flinspach, Jef K. De Brabander, Daniel M. Rosenbaum
Summary: The OX2 orexin receptor (OX2R) is a highly expressed GPCR in the brain that regulates wakefulness and circadian rhythms. This study investigates how the first clinically tested OX2R agonist TAK-925 can activate OX2R in a highly selective manner using cryo-electron microscopy.
NATURE COMMUNICATIONS
(2022)
Article
Clinical Neurology
Shintaro Shibata, Yasunori Oda, Nozomi Ohki, Yuki Ikemizu, Ryunosuke Hayatsu, Yuki Hirose, Masaomi Iyo
Summary: This case report describes a patient who experienced cataplexy and sleep attacks after taking Lemborexant. The patient had no previous diagnosis of narcolepsy, but developed narcolepsy-like symptoms after taking Lemborexant, suggesting that it may trigger such symptoms in patients with hyperactive delirium.
JOURNAL OF CLINICAL SLEEP MEDICINE
(2022)
Review
Immunology
Daniela Latorre, Sallusto Federica, Claudio L. A. Bassetti, Ulf Kallweit
Summary: Narcolepsy is a chronic neurological disorder characterized by excessive daytime sleepiness and cataplexy. Diagnosis and treatment of the disease remain challenging due to its clinical heterogeneity and lack of understanding of its underlying mechanisms. However, significant progress has been made in recent years, opening new perspectives for the field.
SEMINARS IN IMMUNOPATHOLOGY
(2022)
Article
Neurosciences
Shi Zhou, Akira Yamashita, Jingyang Su, Yang Zhang, Wuyang Wang, Liying Hao, Akihiro Yamanaka, Tomoyuki Kuwaki
Summary: The study found that the activity of orexin-deficient mice's neurons increased before the onset of cataplexy-like behavior but decreased during the episode. This suggests that orexin neurons are moderately inhibited during cataplexy, providing insights for better understanding and treatment of cataplexy in narcolepsy patients.
Article
Endocrinology & Metabolism
Takeshi Takarada, Cheng Xu, Hiroki Ochi, Ryota Nakazato, Daisuke Yamada, Saki Nakamura, Ayumi Kodama, Shigeki Shimba, Michihiro Mieda, Kazuya Fukasawa, Kakeru Ozaki, Takashi Iezaki, Koichi Fujikawa, Yukio Yoneda, Rika Numano, Akiko Hida, Hajime Tei, Shu Takeda, Eiichi Hinoi
JOURNAL OF BONE AND MINERAL RESEARCH
(2017)
Article
Neurosciences
Ryota Nakazato, Kenji Kawabe, Daisuke Yamada, Shinsuke Ikeno, Michihiro Mieda, Shigeki Shimba, Eiichi Hinoi, Yukio Yoneda, Takeshi Takarada
JOURNAL OF NEUROSCIENCE
(2017)
Review
Neurosciences
Michihiro Mieda
NEUROSCIENCE RESEARCH
(2017)
Article
Multidisciplinary Sciences
Ryosuke Enoki, Yoshiaki Oda, Michihiro Mieda, Daisuke Ono, Sato Honma, Ken-ichi Honma
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Multidisciplinary Sciences
Emi Hasegawa, Takashi Maejima, Takayuki Yoshida, Olivia A. Masseck, Stefan Herlitze, Mitsuhiro Yoshioka, Takeshi Sakurai, Michihiro Mieda
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Neurosciences
Michihiro Mieda, Emi Hasegawa, Nicoletta Kessaris, Takeshi Sakurai
FRONTIERS IN NEUROSCIENCE
(2017)
Article
Neurosciences
Norifumi Shioda, Yoshiki Imai, Yasushi Yabuki, Wataru Sugimoto, Kouya Yamaguchi, Yanyan Wang, Takatoshi Hikida, IbToshikuni Sasaoka, EMic Hihiro Mieda, Kohji Fukunaga
JOURNAL OF NEUROSCIENCE
(2019)
Article
Multidisciplinary Sciences
Takashi Maejima, Yusuke Tsuno, Shota Miyazaki, Yousuke Tsuneoka, Emi Hasegawa, Md Tarikul Islam, Ryosuke Enoki, Takahiro J. Nakamura, Michihiro Mieda
Summary: The study found that specific deletion of vesicular GABA transporter in AVP neurons led to significant impairment of circadian rhythm and disruption of GABA-mediated synaptic transmission in SCN neurons. While molecular circadian oscillations among SCN neurons did not significantly change, there were significant alterations in the phase relationships between molecular clocks and circadian behavioral activities.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Md Tarikul Islam, Takashi Maejima, Ayako Matsui, Michihiro Mieda
Summary: Self-grooming plays a critical role in maintaining hygiene, regulating body temperature, and responding to stress. This study reveals the crucial involvement of paraventricular hypothalamic nucleus arginine vasopressin-producing neurons in the induction of self-grooming. This finding has significant implications for understanding the regulatory mechanisms of grooming behavior and the pathogenesis of related disorders.
Article
Multidisciplinary Sciences
Fuyuki Asano, Staci J. Kim, Tomoyuki Fujiyama, Chika Miyoshi, Noriko Hotta-Hirashima, Nodoka Asama, Kanako Iwasaki, Miyo Kakizaki, Seiya Mizuno, Michihiro Mieda, Fumihiro Sugiyama, Satoru Takahashi, Shoi Shi, Arisa Hirano, Hiromasa Funato, Masashi Yanagisawa
Summary: Deficiency of SIK3 in GABAergic neurons or NMS-producing neurons delays the arousal peak phase, while a gain-of-function mutant allele of Sik3 in GABAergic neurons advances the activity onset. Furthermore, HDAC4 deficiency shortens the circadian cycle.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Editorial Material
Neurosciences
Michihiro Mieda
Article
Neurosciences
Takako Ohno-Shosaku, Mitsugu Yoneda, Takashi Maejima, Mohan Wang, Yui Kikuchi, Kaito Onodera, Yuji Kanazawa, Chitoshi Takayama, Michihiro Mieda
Summary: This study examined the role of the thalamic reticular nucleus (TRN) in reward-based learning of action sequences. The findings suggest that the TRN plays an important role in action sequence learning, while not affecting simple operant learning.
Article
Multidisciplinary Sciences
Kaito Onodera, Yusuke Tsuno, Yuichi Hiraoka, Kohichi Tanaka, Takashi Maejima, Michihiro Mieda
Summary: Prokineticin 2 (Prok2), a small protein expressed in a subset of neurons in the suprachiasmatic nucleus (SCN), has been implicated as a candidate output molecule controlling multiple circadian rhythms. In this study, Prok2-tTA knock-in mice were generated to specifically express the tetracycline transactivator (tTA) in Prok2 neurons and used for in vivo recording of Ca2+ rhythms. The results showed clear circadian Ca2+ rhythms in SCN Prok2 neurons, with peak activity around midday, coinciding with the rest period of the behavioral rhythm.
SCIENTIFIC REPORTS
(2023)
Article
Neurosciences
Nicole Rigney, Jack Whylings, Michihiro Mieda, Geert J. de Vries, Aras Petrulis
Article
Neurosciences
Yuki C. Saito, Takashi Maejima, Mitsuhiro Nishitani, Emi Hasegawa, Yuchio Yanagawa, Michihiro Mieda, Takeshi Sakurai
JOURNAL OF NEUROSCIENCE
(2018)
