Article
Chemistry, Medicinal
Tsubasa Hino, Tsuyoshi Saitoh, Yasuyuki Nagumo, Naoshi Yamamoto, Noriki Kutsumura, Yoko Irukayama-Tomobe, Yukiko Ishikawa, Ryuji Tanimura, Masashi Yanagisawa, Hiroshi Nagase
Summary: A series of novel naphthalene derivatives were synthesized and evaluated as agonists for orexin receptors. Conformational analysis and docking simulation provided insights into the active conformation and pharmacophore orientation of the compounds, leading to the discovery of a potent candidate for narcolepsy treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Tatsuhiko Fujimoto, Kentaro Rikimaru, Koichiro Fukuda, Hiromichi Sugimoto, Kei Masuda, Norio Ohyabu, Yoshihiro Banno, Norihito Tokunaga, Tetsuji Kawamoto, Yoshihide Tomata, Yasumi Kumagai, Motoo Iida, Yoichi Nagano, Mariko Yoneyama-Hirozane, Yuji Shimizu, Katsunori Sasa, Takashi Ishikawa, Hiroshi Yukitake, Mitsuhiro Ito, Kazunobu Aoyama, Takahiro Matsumoto
Summary: TAK-925, a potent brain-penetrant orexin 2 receptor agonist, showed wake-promoting effects in mice during sleep phase. It is being developed for the treatment of narcolepsy and related disorders.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Konstantina Vraka, Dimitrios Mytilinaios, Andreas P. Katsenos, Anastasios Serbis, Stavros Baloyiannis, Stefanos Bellos, Yannis V. Simos, Nikolaos P. Tzavellas, Spyridon Konitsiotis, Patra Vezyraki, Dimitrios Peschos, Konstantinos I. Tsamis
Summary: This study provides information about the distribution of OX1R in the human hypothalamus. OX1R is mainly found in the lateral hypothalamic area, the lateral preoptic nucleus, the supraoptic nucleus, the dorsomedial nucleus, the ventromedial nucleus, and the paraventricular nucleus. The majority of neurons in these areas (over 80%) express OX1R, with particularly high expression in the lateral tuberal nucleus (over 95% of neurons). These results reveal the distribution of OX1R at the cellular level and discuss its regulatory role in the hypothalamus.
Article
Biochemistry & Molecular Biology
Xiaolong Gao, Mingxin Lyu, Mo Zhang, Shihui Lin, Caihuan Ke
Summary: This study identified and described the structural characteristics and circadian expression patterns of orexin receptor type 2 (OX2R) in the nocturnal marine mollusk, Pacific abalone. It found that the expression levels of OX2R were highest in the intestinal tract and that the feeding behavior of abalone correlated with the expression level of OX2R. These findings provide insights into the molecular mechanisms underlying the feeding rhythm of marine nocturnal organisms.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Behavioral Sciences
Wen-Rui Gao, Xiao-Hong Hu, Kai-Yue Yu, Hong-Yan Cai, Zhao-Jun Wang, Lei Wang, Mei-Na Wu
Summary: Cognitive dysfunction is a main clinical manifestation of Alzheimer's disease (AD). Previous research has found a correlation between elevated orexin level and the progression of AD. Orexin-A treatment has been shown to increase amyloid beta protein (A beta) deposition and worsen spatial memory impairment in mice. Dual orexin receptor (OXR) antagonist has been found to affect A beta level and cognitive dysfunction in AD, but the effects of OX1R or OX2R alone have not been reported. This study investigates the role of OX1R in AD cognitive dysfunction and its possible mechanism.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Xin Guo, Jing Wen, Qianqian Gao, Yuyan Zhao, Yue Zhao, Chunyu Wang, Na Xu, Yaozhong Shao, Xiaocen Chang
Summary: Orexin-A/OX1R promotes cortisol secretion by modulating the mTOR/p70S6K1/autophagy signaling pathway, providing potential therapeutic targets for hypercortisolism treatment.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Rosa Maria Vitale, Fabio Arturo Iannotti, Aniello Schiano Moriello, Lea Tunisi, Fabiana Piscitelli, Ranjev Savopoulos, Luigia Cristino, Luciano De Petrocellis, Pietro Amodeo, Roy Gray, Vincenzo Di Marzo
Summary: The study provides the first evidence that CBD acts as an antagonist at the OX1R receptor, supporting its potential use in addictive disorders and/or body weight regulation.
Article
Biochemistry & Molecular Biology
E. A. Sekste, A. A. Lebedev, E. R. Bychkov, M. Airapetov, K. E. Gramota, I. Yu Tissen, P. D. Shabanov
Summary: This study investigates the expression level of orexin receptor mRNA in different brain regions of rats prone to impulsive behavior in a gambling addiction model. The results show that the OX1R gene expression is higher in the hypothalamus and hippocampus, but not in the prefrontal cortex. In contrast, no significant changes are observed in the level of OX2R mRNA in any of the brain regions. These findings suggest that OX1R is involved in mediating impulsive behavior and the choice of positive reinforcement in the hypothalamus and hippocampus.
BIOCHEMISTRY MOSCOW-SUPPLEMENT SERIES B-BIOMEDICAL CHEMISTRY
(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
Medicine, Research & Experimental
Ying-Jie Dong, Ning-Hua Jiang, Liang-Hui Zhan, Xi Teng, Xi Fang, Min-Qiu Lin, Zhi-Yi Xie, Rong Luo, Lin-Zi Li, Bo Li, Bei-Bei Zhang, Gui-Yuan Lv, Su-Hong Chen
Summary: The study demonstrated the sleep-improving effect of Modified Suanzaoren Decoction (MSZRD) on mice with insomnia, by regulating the expression of Orexin-A and affecting the homeostasis of HPA axis and the release of related neurotransmitters in mice with insomnia.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Tsuyoshi Saitoh, Takeshi Sakurai
Summary: The neuropeptide orexin/hypocretin is important in regulating various physiological processes and its dysregulation has been implicated in hypersomnia, particularly narcolepsy. Small-molecule orexin receptor agonists have emerged as potential therapeutics for these disorders and recent advancements in their design and synthesis have been summarized in this review, focusing on peptidic and small-molecule OX2R-selective, dual, and OX1R-selective agonists. The review discusses the structural features, pharmacological properties, and potential therapeutic applications of these agonists.
Article
Ophthalmology
Arthur A. DeCarlo, Nathan Hammes, Philip L. Johnson, Anantha Shekhar, Brian C. Samuels
Summary: The study found that orexin receptors have the potential to modulate intraocular pressure (IOP), intracranial pressure (ICP), and translaminar pressure difference (TLPD), reducing asynchronous changes caused by central nervous system activation.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Takashi Maruyama, Yoichi Ueta
Summary: Orexin-A and -B are neuropeptides synthesized in the lateral hypothalamus and perifornical area, and play a crucial role in various physiological functions. The orexin system is mediated by specific receptors and is involved in arousal, feeding, reward, and thermogenesis.
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
Neurosciences
Joseph S. Lonstein, Katrina Linning-Duffy, Yuping Tang, Anna Moody, Lily Yan
Summary: The study showed that daytime light intensity can alter the central orexin system of both male and female grass rats, sometimes in a sex-specific manner, providing insights into how daytime light intensity impacts functions regulated by orexin.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Endocrinology & Metabolism
Hanna Grasshoff, Helge Mueller-Fielitz, Godwin K. Dogbevia, Jakob Koerbelin, Jacqueline Bannach, Carl M. G. Vahldieck, Kristina Kusche-Vihrog, Olaf Joehren, Oliver J. Mueller, Ruben Nogueiras, Vincent Prevot, Markus Schwaninger
Summary: By studying the combination of truncated promoters of brain endothelial-specific genes and short regulatory elements, new regulatory sequences have been developed that efficiently control gene expression in brain endothelial cells with greater strength and specificity.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Nutrition & Dietetics
Marina Colom-Pellicer, Romina M. Rodriguez, Jorge R. Soliz-Rueda, Leonardo Vinicius Monteiro de Assis, Elia Navarro-Masip, Sergio Quesada-Vazquez, Xavier Escote, Henrik Oster, Miquel Mulero, Gerard Aragones
Summary: Consumption of grape seed proanthocyanidin extract (GSPE) can restore the diurnal rhythm of white adipose tissue (WAT) and provide an innovative time-dependent strategy for the treatment of obesity and metabolic diseases.
Review
Biochemistry & Molecular Biology
Achim Kramer, Tanja Lange, Claudia Spies, Anna-Marie Finger, Daniela Berg, Henrik Oster
Summary: Circadian medicine, an emerging field, aims to utilize the mechanisms of the circadian clock for clinical diagnosis, treatment, and prevention. While it has significant health benefits over standard care, there are still open questions and challenges in the development of this field.
Article
Oncology
Hendrik Ungefroren, Isabel Thuerling, Benedikt Faerber, Tanja Kowalke, Tanja Fischer, Leonardo Vinicius Monteiro De Assis, Ruediger Braun, Darko Castven, Henrik Oster, Bjoern Konukiewitz, Ulrich Friedrich Wellner, Hendrik Lehnert, Jens-Uwe Marquardt
Summary: Intratumoral heterogeneity is an intrinsic feature of malignant tumors that can lead to treatment failure or relapse. Epithelial-mesenchymal transition and its reverse process, MET, drive cellular plasticity and tumor progression. In pancreatic ductal adenocarcinoma, single cell-derived clonal cultures with different EMT phenotypes were generated, which were associated with tumorigenic potential and circadian clock function.
Article
Clinical Neurology
H. Findeis, H. Oster, M. Bauer, P. Ritter
Summary: This article compares and discusses the current data situation on chronobiological aspects of bipolar disorder. The research suggests a direct connection between disruption of the circadian rhythm and the development and progression of bipolar disorder, particularly in relation to chronotype, environmental factors such as light, and sleep disorders. However, there is currently no evidence to prove the specificity of these findings for bipolar disorder.
Review
Physiology
Leonardo Vinicius Monteiro de Assis, Muenevver Demir, Henrik Oster
Summary: This review focuses on the role of circadian rhythms in the liver and their impact on the development of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The disruption of circadian rhythms and its potential consequences are discussed, as well as the potential use of the clock system in prevention and treatment of NAFLD/NASH. Attention to circadian timing may provide new avenues for optimizing therapies and targeting these prevalent disorders.
Review
Physiology
Iwona Olejniczak, Kimberly Begemann, Ines Wilhelm, Henrik Oster
Summary: Circadian clocks play a crucial role in regulating physiology and behavior, particularly in the central reward system. They impact neurotransmitter signaling, neuroendocrine circuits, and sensitivity to external stimuli. Disruption of circadian rhythms can affect reward signaling, leading to the development of behavioral and substance use disorders. This review summarizes current knowledge on the interaction between circadian clocks and reward, highlighting the effects of chronodisruption on reward signaling in animal models. The translation of these findings to human reward (dys-) function and the clinical implications are discussed, along with the challenges and approaches in incorporating circadian medicine concepts into the therapy of substance use disorders.
Review
Physiology
Rodrigo Chamorro, Celine Jouffe, Henrik Oster, N. Henriette Uhlenhaut, Sebastian M. Meyhoefer
Summary: This review article discusses the circadian clock's role in regulating physiological and behavioral functions, especially in relation to food intake and metabolic regulation. It emphasizes the importance of meal timing in controlling appetite and metabolic responses. The article provides a fundamental research axis for maintaining a healthy eating behavior by exploring the mechanisms of food intake regulation and focusing on the crucial role of the circadian clock.
Article
Endocrinology & Metabolism
Kimberly Begemann, Isabel Heyde, Pia Witt, Julica Inderhees, Brinja Leinweber, Christiane E. Koch, Olaf Joehren, Rebecca Oelkrug, Arkadiusz Liskiewicz, Timo D. Mueller, Henrik Oster
Summary: Snacking during the rest phase leads to weight gain and disruption of metabolic circadian rhythms, while snacking during the active phase does not have the same effect.
MOLECULAR METABOLISM
(2023)
Review
Physiology
Hong-Viet V. Ngo, Henrik Oster, Christina Andreou, Jonas Obleser
Summary: Circadian rhythms are inherent in all organisms and have an impact on various aspects of physiology and behavior in response to the 24-hour day-night cycle. The review focuses on the potential role of circadian disruption in auditory hallucinations, a cardinal symptom of psychosis. The dysbalance in excitation and inhibition within cortical networks, leading to disinhibition of dopaminergic signaling, is highlighted as a central physiological mechanism. Two avenues for experimentally intervening on circadian influences to alleviate hallucinations in psychotic disorders are proposed.
Review
Physiology
Dieter Kunz, Henrik Oster, Oliver Rawashdeh, Wolf-Julian Neumann, Thomas Muente, Daniela Berg
Summary: The prevalence of neurodegenerative diseases, particularly Parkinson's disease, in the global north is increasing at an alarming rate, with some even calling it a pandemic. While lifestyle factors are known to contribute, the role of circadian rhythms in these diseases has not been extensively explored. Sleep and circadian rhythm disruption have been found to play a key role in neurodegeneration, particularly during the early stages of the disease. This review summarizes the current knowledge on sleep and circadian rhythm disruptions in neurodegenerative diseases, with a focus on molecular aspects and therapeutic potentials, providing valuable insights into the pathogenesis and potential treatment interventions.
Review
Neurosciences
Marianne Lehmann, Katharina Haury, Henrik Oster, Mariana Astiz
Summary: Glucocorticoids (GCs) play a crucial role in the development of the circadian system during the perinatal period and continue to regulate various functions such as energy metabolism and behavior in adulthood. This article explores the bidirectional interaction between GCs and the circadian clock at the molecular and systemic levels, with a focus on the influence of GC rhythm on the master clock in the suprachiasmatic nuclei (SCN) of the hypothalamus during development and in the adult system.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Biology
Iwona Olejniczak, Violetta Pilorz, Henrik Oster
Summary: This review summarizes the development and maturation of circadian clocks in humans and experimental rodents, including their changes during embryonic development, after birth, and during puberty, adolescence, and aging. The focus is on the circadian regulation of reproductive systems as major organizers of life stages and lifespan. The differences between sexes are also discussed, and potential areas for future research are outlined. Finally, potential options for medical applications of lifespan chronobiology are discussed.
Editorial Material
Nutrition & Dietetics
Henrik Oster, Ines Chaves
Article
Neurosciences
Yang He, Jun Tang, Meng Zhang, Junjie Ying, Dezhi Mu
Summary: This study investigated the protective effects and mechanisms of human placenta derived mesenchymal stem cells (hPMSCs) transplantation in a rat model of hypoxic-ischemic encephalopathy (HIE). The results showed that hPMSCs transplantation reduced apoptosis and improved long-term neurological prognosis. Furthermore, the downregulation of Sema 3A/NRP-1 expression and activation of the PI3K/Akt/mTOR signaling pathway played a key role in the protective effects of hPMSCs.
Article
Neurosciences
Emily L. Isenstein, Edward G. Freedman, Jiayi Xu, Ian A. DeAndrea-Lazarus, John J. Foxe
Summary: This study evaluated electrophysiological discrimination of parametric somatosensory stimuli in healthy young adults to understand how the brain processes the duration of tactile information. The results showed that participants did not electrophysiologically discriminate between 100 and 115 ms, but they exhibited distinct electrophysiological responses when the deviant stimuli were 130, 145, and 160 ms. These findings contribute to a better understanding of tactile sensitivity in different clinical conditions.
Article
Neurosciences
Juliana R. Souza, Ludmila Lima-Silveira, Daniela Accorsi-Mendonca, Benedito H. Machado
Summary: This study demonstrates that A2A receptors play a crucial role in modulating synaptic transmission in the NTS neurons and are required for the enhancement of glutamatergic transmission observed under short-term sustained hypoxia conditions.
Article
Neurosciences
Miki Hashizume, Rina Ito, Rie Suge, Yasushi Hojo, Gen Murakami, Takayuki Murakoshi
Summary: The basolateral amygdaloid complex (BLA) is closely involved in the formation of emotional memories, including both aversive memory and contextual fear memory. Acute sleep deprivation (SD) disrupts the acquisition of tone-associated fear memory in juvenile rats, but has no significant effect on contextual fear memory. Slow network oscillation in the amygdala contributes to the formation of amygdala-dependent fear memory in relation to sleep.
Article
Neurosciences
Qunxian Wang, Shipeng Guo, Dongjie Hu, Xiangjun Dong, Zijun Meng, Yanshuang Jiang, Zijuan Feng, Weihui Zhou, Weihong Song
Summary: GSDME plays a crucial role in the pathogenesis of Alzheimer's disease by regulating the switch from apoptosis to pyroptosis and participating in neuroinflammatory response. Knockdown of GSDME has been shown to improve cognitive impairments, indicating that GSDME could be a therapeutic target for Alzheimer's disease.
