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
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
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
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.
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
Sara Alvente, Chiara Berteotti, Stefano Bastianini, Viviana Lo Martire, Gabriele Matteoli, Alessandro Silvani, Giovanna Zoccoli
Summary: The study found that in orexin-deficient mouse models, higher arterial pressure during sleep and smaller differences in arterial pressure between sleep and wakefulness are mediated by alterations in cardiovascular sympathetic control.
Article
Chemistry, Medicinal
Dehui Zhang, David A. Perrey, Ann M. Decker, Tiffany L. Langston, Vijayakumar Mavanji, Danni L. Harris, Catherine M. Kotz, Yanan Zhang
Summary: The study identified a promising dual small molecule agonist that can increase wakefulness and alleviate narcolepsy symptoms, with positive effects demonstrated in experiments on elderly mice, supporting the development of orexin agonists as potential treatments for orexin-deficient disorders in the future.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Takuya Ogawa, Yuta Kajiyama, Hideaki Ishido, Shigeru Chiba, Gajanan S. Revankar, Tomohito Nakano, Seira Taniguchi, Takashi Kanbayashi, Kensuke Ikenaka, Hideki Mochizuki
Summary: This study investigated the association between cerebrospinal fluid (CSF) orexin levels and sleep disturbances in patients with Parkinson's disease (PD). The results showed decreased CSF orexin levels in patients with PD, but these levels did not correlate with any clinical characteristics. The study suggests that understanding the reciprocal role of orexin among other neurotransmitters may provide a better treatment strategy for sleep disturbance in patients with PD.
Article
Clinical Neurology
Ming-Fung Wu, Thomas C. Thannickal, Songlin Li, Ronald McGregor, Yuan-Yang Lai, Jerome M. Siegel
Summary: Long-term use of sodium oxybate (SXB) can alleviate cataplexy and sleepiness in narcolepsy. However, unlike opioids, SXB increases the size of Hcrt neurons, decreases Hcrt levels in the hypothalamus, and reduces tyrosine hydroxylase levels in the locus coeruleus. Although there are some similar effects on narcoleptic symptoms, SXB does not produce anatomical changes similar to opioids.
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)
Review
Neurosciences
Sachin Kumar, Tapan Behl, Aayush Sehgal, Sukhbir Singh, Neelam Sharma, Saurabh Bhatia, Ahmed Al-Harassi, Mohammed M. Abdel-Daim, Simona Bungau
Summary: This study reviewed the changes in the orexinergic system in parkinsonian subjects and found dysfunctioning of this system to be linked with non-motor symptoms (sleep abnormalities) in PD. Orexinergic neurons' behavior is modulated by various factors, and orexin antagonists have been shown to improve abnormal sleep patterns. Since the orexinergic system plays a role in several psychological and neurological disorders, targeting this system could potentially help manage these disorders.
NEUROTOXICITY RESEARCH
(2021)
Article
Clinical Neurology
Lucie Barateau, Regis Lopez, Sofiene Chenini, Anna Laura Rassu, Lytissia Mouhli, Cloe Dhalluin, Isabelle Jaussent, Yves Dauvilliers
Summary: This study aimed to determine the factors associated with disrupted nocturnal sleep (DNS) in patients with narcolepsy type 1 (NT1) and evaluate the effect of medication on DNS and its severity. The results showed that DNS severity was associated with disease severity, sleep quality, and sleep instability. Treatment led to improvements in DNS and reduced sleepiness and depressive symptoms.
Article
Cell Biology
Matthew Dawson, Dylan J. Terstege, Naila Jamani, Mio Tsutsui, Dmitrii Pavlov, Raluca Bugescu, Jonathan R. Epp, Gina M. Leinninger, Derya Sargin
Summary: The hypothalamus is crucial in regulating social behavior by encoding internal states. Hypocretin/orexin neurons in the hypothalamus, initially known for their role in sleep and appetite regulation, also play a key role in emotional and motivated behaviors. However, their involvement in social behavior is still not well understood.
Article
Neurosciences
Saara Nuutinen, Tiia Maki, Stanislav Rozov, Pia Backstrom, Petri Hyytia, Petteri Piepponen, Pertti Panula
Editorial Material
Neurosciences
Helmut L. Haas, Pertti Panula
Article
Neurosciences
Regis Parmentier, Yan Zhao, Magali Perier, Hideo Akaoka, Minnamaija Lintunen, Yiping Hou, Pertti Panula, Takeshi Watanabe, Patricia Franco, Jian-Sheng Lin
Article
Neurosciences
Shamsiiat Abdurakhmanova, Karthik Chary, Mikko Kettunen, Alejandra Sierra, Pertti Panula
JOURNAL OF COMPARATIVE NEUROLOGY
(2017)
Article
Multidisciplinary Sciences
Henri A. J. Puttonen, Svetlana Semenova, Maria Sundvik, Pertti Panula
SCIENTIFIC REPORTS
(2017)
Article
Pharmacology & Pharmacy
Diego Baronio, Henri A. J. Puttonen, Maria Sundvik, Svetlana Semenova, Essi Lehtonen, Pertti Panula
BRITISH JOURNAL OF PHARMACOLOGY
(2018)
Article
Multidisciplinary Sciences
Madhusmita Priyadarshini Sahu, Yago Pazos-Boubeta, Ceren Pajanoja, Stanislav Rozov, Pertti Panula, Eero Castren
SCIENTIFIC REPORTS
(2019)
Review
Pharmacology & Pharmacy
Pertti Panula
BRITISH JOURNAL OF PHARMACOLOGY
(2020)
Article
Behavioral Sciences
Shamsiiat Abdurakhmanova, Svetlana Semenova, T. Petteri Piepponen, Pertti Panula
GENES BRAIN AND BEHAVIOR
(2019)
Article
Multidisciplinary Sciences
Jaakko T. Leinonen, Yu-Chia Chen, Jana Pennonen, Leevi Lehtonen, Nella Junna, Taru Tukiainen, Pertti Panula, Elisabeth Widen
SCIENTIFIC REPORTS
(2019)
Article
Neurosciences
Yu-Chia Chen, Diego Baronio, Svetlana Semenova, Shamsiiat Abdurakhmanova, Pertti Panula
JOURNAL OF NEUROSCIENCE
(2020)
Article
Physiology
Diego Baronio, Yu-Chia Chen, Amanda R. Decker, Louise Enckell, Blanca Fernandez-Lopez, Svetlana Semenova, Henri A. J. Puttonen, Robert A. Cornell, Pertti Panula
Summary: The study aimed to investigate the potential roles of vesicular monoamine transporter 2 (Vmat2) in brain monoamine regulation, turnover, behaviour, and development using a novel zebrafish model. Results showed that Vmat2 deficiency led to increased monoamine turnover, upregulation of amine-synthesising enzymes, and downregulation of genes involved in brain development. This zebrafish vmat2 mutant strain could be a valuable model for studying the impact of monoamine transport on brain development and function, as well as for drug screening purposes.
Article
Cell Biology
Diego Baronio, Yu-Chia Chen, Pertti Panula
Summary: Deficiency of monoamine oxidase (MAO) and imbalanced levels of brain monoamines are associated with developmental delay, neuropsychiatric disorders, and aggressive behavior. This study introduces a novel genetic model using zebrafish to study the effects of mao loss of function. The results demonstrate alterations in neurotransmitter systems, expression of relevant genes, and behavioral changes in mao mutants.
DISEASE MODELS & MECHANISMS
(2022)
Article
Behavioral Sciences
Laura DeOliveira-Mello, Diego Baronio, Pertti Panula
Summary: Prenatal exposure to VPA in zebrafish leads to delay in visual system development and sleep disturbances, along with a reduction in certain cell populations associated with ASD.
Article
Neurosciences
Yuxiao Yao, Diego Baronio, Yu-Chia Chen, Congyu Jin, Pertti Panula
Summary: This study found that the absence of the hrh1 gene in zebrafish leads to deficits in the dopaminergic and hypocretin systems during early development, but these deficits are compensated for in adulthood. However, adult fish exhibit impaired sociability and anxious-like behavior, along with downregulation of choline O-acetyltransferase and LIM homeodomain transcription factor Islet1.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Physiology
Minyu Zhang, Biyang Xiao, Xiaoqi Chen, Bingming Ou, Songtao Wang
Summary: Non-alcoholic fatty liver disease (NAFLD) is closely related to bile acid and gut microbiota disorders. Exercise plays an important role in maintaining the homeostasis of the enterohepatic circulation and the health of the host gut microbiota by regulating the composition and function of the bile acid pool in the enterohepatic axis. Exercise has been recommended as a first-line intervention for NAFLD, and regulating bile acids through exercise may be a promising treatment strategy.
