Article
Neurosciences
Zhe Yu, Alexandre Kisner, Amy Bhatt, Abigail M. Polter, Paul J. Marvar
Summary: This study examined the role of angiotensin II receptor type 1 (AT1R) neurons in the central amygdala (CeA) in fear and anxiety-related behavior using AT1R transgenic mice. It was found that AT1R+ neurons were localized to GABA expressing neurons in the CeL, and their deletion enhanced extinction learning. Furthermore, the application of angiotensin II increased inhibitory synaptic currents and decreased the excitability of CeL-AT1R+ neurons. These findings provide new insights into the neurobiological mechanisms underlying fear extinction.
Article
Neurosciences
Jazmine D. W. Yaeger, Kevin T. Krupp, Benjamin M. Jacobs, Benard O. Onserio, Brandon L. Meyerink, Jacob T. Cain, Patrick J. Ronan, Kenneth J. Renner, Ralph J. DiLeone, Cliff H. Summers
Summary: This study investigates the role of Orx1 receptors in stress-induced phenotypes in mice and finds that antagonism of Orx1 receptors can modulate behavioral responses and lead to reorganization of gene expression, providing evidence for a receptor-driven mechanism that balances stress and anti-stress responses.
BIOLOGICAL PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Marcin Piechota, Urszula Skupio, Malgorzata Borczyk, Barbara Ziolkowska, Slawomir Golda, Lukasz Szumiec, Klaudia Szklarczyk-Smolana, Wiktor Bilecki, Jan Manuel Rodriguez Parkitna, Michal Korostynski
Summary: The expression of Ca2+/Calmodulin-Dependent Protein Kinase I gamma (Camk1g) is regulated by stress and glucocorticoid receptors (GR) in neuronal cells of the limbic system. It is involved in anxiety-related behaviors and responses conditioned by aversive stimuli.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Marc Ten-Blanco, Africa Flores, Inmaculada Pereda-Perez, Fabiana Piscitelli, Cristina Izquierdo-Luengo, Luigia Cristino, Julian Romero, Cecilia J. Hillard, Rafael Maldonado, Vincenzo Di Marzo, Fernando Berrendero
Summary: Anxiety and stress disorders often involve an inability to extinguish learned fear responses. This study suggests that the endogenous cannabinoid system is involved in this impairment and that dysregulation of the orexin system may contribute to anxiety disorders characterized by pathological fear.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Chemistry, Multidisciplinary
Mitjan Morr, Jeanine Noell, Daphne Sassin, Jule Daniels, Alexandra Philipsen, Benjamin Becker, Birgit Stoffel-Wagner, Rene Hurlemann, Dirk Scheele
Summary: Loneliness may contribute to vulnerability to intrusive memories after trauma in healthy men, with altered limbic processing of fear signals being a potential underlying mechanism. Lonely men showed more intrusions and altered amygdala activity, while loneliness did not have the same impact on women.
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
Behavioral Sciences
Lucja Wiktorowska, Wiktor Bilecki, Magdalena Tertil, Lucja Kudla, Lukasz Szumiec, Marzena Mackowiak, Ryszard Przewlocki
Summary: The study demonstrates that astrocytic GR in the CeA plays a crucial role in promoting aversive memory consolidation and certain aspects of anxiety behavior.
BEHAVIOURAL BRAIN RESEARCH
(2021)
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
Biochemistry & Molecular Biology
Einat Elharrar, Yahav Dikshtein, Sapir Meninger-Mordechay, Yehuda Lichtenstein, Gal Yadid
Summary: Recent research shows that inhibiting PARP-1 activity can interfere with fear conditioning and reduce freezing behavior. By controlling the pharmacokinetic timing, it is possible to specifically disrupt cue-associated fear memories without interfering with other natural memories.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
Peter Wohlfahrt, Dominik Jenca, Vojtech Melenovsky, Petr Jarolim, Dana Dlouha, Marek Sramko, Martin Kotrc, Michael Zelizko, Jolana Mrazkova, Jan Pitha, Vera Adamkova, Josef Kautzner
Summary: The lack of hypocretin/orexin signaling is associated with increased mortality risk after myocardial infarction (MI). The allele variant that attenuates this signaling is associated with a higher risk of death after MI.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Review
Clinical Neurology
Maria P. Mogavero, Alessandro Silvani, Giuseppe Lanza, Lourdes M. DelRosso, Luigi Ferini-Strambi, Raffaele Ferri
Summary: After describing orexins and their roles in sleep and medical disorders, the article discusses the clinical evidence on the effects of DORAs and SORAs on insomnia to provide recommendations for further assessment in personalized and precision medicine. Trials with orexin receptor antagonists have shown potential as a valid therapeutic option for insomnia in various medical conditions, but more studies are needed to determine the most suitable options for different patient populations.
NATURE AND SCIENCE OF SLEEP
(2023)
Article
Cell Biology
Andrew S. Huhn, Patrick H. Finan, Charlene E. Gamaldo, Alexis S. Hammond, Annie Umbricht, Cecilia L. Bergeria, Eric C. Strain, Kelly E. Dunn
Summary: This study examined the use of a dual-orexin receptor antagonist in opioid withdrawal and found that it may have potential benefits for improving sleep and withdrawal outcomes.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
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)
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.
Article
Behavioral Sciences
Ihori Kobayashi, Patrick A. Forcelli
Summary: The study found that intervention with the dual orexin receptor antagonist suvorexant did not have the expected effects on extinction memory and sleep. Higher percentages of REM sleep were associated with poorer extinction memory recall and stronger fear responses. Additionally, the fear extinction training protocol used in this study did not lead to complete fear extinction.
BEHAVIOURAL BRAIN RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
A. I. Molosh, E. T. Dustrude, J. L. Lukkes, S. D. Fitz, I. F. Caliman, A. R. R. Abreu, A. D. Dietrich, W. A. Truitt, L. Ver Donck, M. Ceusters, J. M. Kent, P. L. Johnson, A. Shekhar
MOLECULAR PSYCHIATRY
(2020)
Article
Biochemistry & Molecular Biology
Yu Xu, Lucas Cantwell, Andrei I. Molosh, Leigh D. Plant, Dimitris Gazgalis, Stephanie D. Fitz, Erik T. Dustrude, Yuchen Yang, Takeharu Kawano, Sumanta Garai, Sami F. Noujaim, Anantha Shekhar, Diomedes E. Logothetis, Ganesh A. Thakur
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Clinical Neurology
J. L. Lukkes, H. P. Drozd, S. D. Fitz, A. I. Molosh, D. W. Clapp, A. Shekhar
JOURNAL OF NEURODEVELOPMENTAL DISORDERS
(2020)
Article
Clinical Neurology
Cristian S. Bernabe, Izabela F. Caliman, William A. Truitt, Andrei Molosh, Christopher A. Lowry, Anders Hay-Schmidt, Anantha Shekhar, Philip L. Johnson
JOURNAL OF PSYCHOPHARMACOLOGY
(2020)
Article
Chemistry, Medicinal
Cathy Preville, Pascal Bonaventure, Tatiana Koudriakova, Brian Lord, Diane Nepomuceno, Michele Rizzolio, Neelakandha Mani, Kevin J. Coe, Anthony Ndifor, Christine Dugovic, Curt A. Dvorak, Heather Coate, Daniel J. Pippel, Anne Fitzgerald, Brett Allison, Timothy W. Lovenberg, Nicholas Carruthers, Brock T. Shireman
ACS MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Pharmacology & Pharmacy
Lien Wang, Christine Dugovic, Sujin Yun, Allison White, Brian Lord, Curt Dvorak, Changlu Liu, Timothy Lovenberg, Pascal Bonaventure
EUROPEAN JOURNAL OF PHARMACOLOGY
(2020)
Article
Multidisciplinary Sciences
Grace Woodruff, Naomi Phillips, Cassiano Carromeu, Oivin Guicherit, Alistair White, McCay Johnson, Fabian Zanella, Blake Anson, Timothy Lovenberg, Pascal Bonaventure, Anthony W. Harrington
Article
Chemistry, Medicinal
Curt A. Dvorak, Dale A. Rudolph, Diane Nepomuceno, Lisa Dvorak, Brian Lord, Ian Fraser, Pascal Bonaventure, Timothy Lovenberg, Nicholas I. Carruthers
Summary: A novel dual 5-HT7/5-HT2 receptor antagonist, 3-(4-Fluorophenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene (4j), showed high affinity for both receptors with potential therapeutic efficacy in in vivo models for central 5-HT7 and 5-HT2A activity.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Behavioral Sciences
Andrew T. Gargiulo, Varuna Jasodanand, Sandra Luz, Lauren O'Mara, Leszek Kubin, Richard J. Ross, Seema Bhatnagar, Laura A. Grafe
Summary: Sleep disruptions are hallmarks in stress-related disorders, affecting female populations disproportionately. This study found that repeated stress exposure led to persistent disruptions in sleep in female rats, with increased time spent awake, decreased SWS and REMS, and exaggerated motor responses during waking from REMS. Male rats, on the other hand, showed transient effects of stress on sleep.
STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS
(2021)
Article
Behavioral Sciences
Andrew T. Gargiulo, Laurel M. Peterson, Laura A. Grafe
Summary: During the COVID-19 pandemic, women experienced worse sleep quality compared to men. Pandemic-related coping strategies were associated with sleep quality, with primary control engagement coping linked to better sleep and involuntary engagement coping linked to poorer sleep quality.
BRAIN AND BEHAVIOR
(2021)
Article
Pharmacology & Pharmacy
Anthony W. Harrington, Changlu Liu, Naomi Phillips, Diane Nepomuceno, Chester Kuei, Joseph Chang, Weixuan Chen, Steven W. Sutton, Daniel O'Malley, Ly Pham, Xiang Yao, Siquan Sun, Pascal Bonaventure
Summary: The study suggests that oxysterols, including 24S-HC, could be physiological activators for GPR17, regulating oligodendrocyte progenitor cell differentiation and myelination through receptor activation.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Meeting Abstract
Neurosciences
Benjamin Throesch, Michelle Wennerholm, Pascal Bonaventure, Grace Woodruff
NEUROPSYCHOPHARMACOLOGY
(2022)
Meeting Abstract
Neurosciences
Benjamin Throesch, Michelle Wennerholm, Pascal Bonaven-Ture, Grace Woodruff
NEUROPSYCHOPHARMACOLOGY
(2021)
Meeting Abstract
Neurosciences
Vivien Zell, Pascal Bonaventure, Grace Woodruff, Wayne Drevets, Bartosz Balana
NEUROPSYCHOPHARMACOLOGY
(2021)
Meeting Abstract
Neurosciences
Jose Matta, Christine Dugovic, Sujin Yun, Ian Fraser, Daniel Knowland, Weston Davini, Ryan Wyatt, Pascal Bonaventure
NEUROPSYCHOPHARMACOLOGY
(2021)