Article
Neurosciences
Francisco Ros-Bernal, Isis Gil-Miravet, Jorge Luceron, Monica Navarro-Sanchez, Esther Castillo-Gomez, Andrew L. Gundlach, Francisco E. Olucha-Bordonau
Summary: This study investigated the neurodevelopmental consequences of RLN3 innervation in the septal area during postnatal development in rats. The results showed that RLN3 network development in the septal area began between P17 and P20 and was correlated with the onset of hippocampal theta rhythm and associated learning processes.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Neurosciences
Anna Blasiak, Anna Gugula, Andrew L. L. Gundlach, Francisco E. E. Olucha-Bordonau, Francesco Aniello, Aldo Donizetti
Summary: This review investigates the evolutionary conservation of relaxin family peptide and receptor gene expression and their role in brain neural circuits. The use of zebrafish as a model organism provides a potential advantage in exploring the diversification and conservation of relaxin family ligands and receptor systems.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Behavioral Sciences
Francisco J. Flores-Ramirez, Jessica M. Illenberger, Glenn E. Pascasio, Alessandra Matzeu, Barbara J. Mason, Remi Martin-Fardon
Summary: Alcohol use disorder (AUD), a treatment-resistant medical condition, was studied using a dual orexin receptor antagonist, suvorexant, which was found to decrease alcohol intake and prevent stress-induced alcohol-seeking behavior in male rats with a history of alcohol dependence. Targeting the orexin system shows promise for the treatment of substance use disorders, including AUD.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2022)
Article
Psychiatry
Giuseppe Giannotti, Francesca Mottarlini, Jasper A. Heinsbroek, Mitchel R. Mandel, Morgan H. James, Jamie Peters
Summary: As the number of opioid-related deaths continues to rise, the search for new treatments for opioid use disorder (OUD) is becoming increasingly urgent. Two separate hypothalamic neuropeptide systems have shown promise in preclinical models of OUD. The oxytocin system, originating in the paraventricular nucleus (PVN), may have a protective effect against OUD severity, while the orexin system, originating in the lateral hypothalamus (LH), may exacerbate OUD severity. Therefore, activating the oxytocin system or inhibiting the orexin system could be potential therapeutic strategies. However, the specific role of these systems in specific OUD outcomes is not yet fully understood.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Hannah S. Ballas, Samantha M. Wilfur, Nicole A. Freker, Kah-Chung Leong
Summary: Factors such as stress and anxiety can trigger alcohol-dependent behavior and relapse, and investigating potential pharmacological interventions is important. Previous studies suggest that oxytocin has anxiolytic potential and can disrupt stress-induced ethanol-seeking behavior, specifically within the central amygdala.
Article
Clinical Neurology
Haleh Amirteymori, Saeideh Karimi-Haghighi, Mahboobeh Mirmohammadi, Maryam Majidinezhad, Elahe Khosrowabadi, Abbas Haghparast
Summary: This study investigates the role of the hypocretin/orexin system in treating psychostimulant addiction. The findings suggest that modulation of this system has therapeutic potential in the extinction and reinstatement of Meth-induced conditioned place preference.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2023)
Article
Endocrinology & Metabolism
Bin Li, Leilei Chang, Xiaochun Peng
Summary: Orexin, mainly synthesized in the lateral hypothalamus/perifornical area, is implicated in feeding, sleep-wake cycles, and reward. Activation of OX2R in the NAc shell has been found to play a role in regulating acute stress-induced anxiety, suggesting OX2R antagonist as a potential treatment for anxiety disorders.
PSYCHONEUROENDOCRINOLOGY
(2021)
Article
Neurosciences
Agata Szlaga, Patryk Sambak, Anna Gugula, Aleksandra Trenk, Andrew L. Gundlach, Anna Blasiak
Summary: The nucleus incertus (NI) is a brainstem structure involved in the control of arousal, stress responses, and locomotor activity. This study found that NI neurons express dopamine type 2 (D2) receptors and receive strong catecholaminergic innervation. Activation of D2 receptors in the NI had excitatory and inhibitory effects on neuronal activity, which were cell-type specific. These findings highlight the importance of the NI in integrating arousal-related neuronal information.
Article
Neurosciences
Aleksandra Trenk, Magdalena Walczak, Agata Szlaga, Kamil Pradel, Anna Blasiak, Tomasz Blasiak
Summary: Theta oscillations play a key role in memory formation, sensorimotor integration, and control of locomotion and behavioral states. This study investigated the generation and synchronization of theta oscillations in the brain, particularly focusing on the interactions between brain nuclei and the medial septum (MS). The researchers discovered distinct populations of neurons in the pontine nucleus incertus (NI) that fire action potentials in different manners and have different connections with the MS. These findings provide insights into the mechanisms of theta rhythm generation and transmission in the brain.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Chemistry, Medicinal
Elaine A. Gay, Dongliang Guan, Kalynn Van Voorhies, Vineetha Vasukuttan, Kelly M. Mathews, Joyce Besheer, Chunyang Jin
Summary: This study reports the discovery of the first small molecule antagonists of RXFP3 and identifies RLX-33 as a potential drug for blocking the relaxin-3/RXFP3 system. Further experiments demonstrate the selectivity and pharmacokinetic properties of RLX-33.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Qingxiao Hong, Wenjin Xu, Zi Lin, Jing Liu, Weisheng Chen, Huaqiang Zhu, Miaojun Lai, Dingding Zhuang, Zemin Xu, Dan Fu, Wenhua Zhou, Huifen Liu
Summary: Epigenetic modifications, such as DNA methylation, play a crucial role in regulating gene expression and may influence neuroplasticity and drug-induced aberrant behaviors. The study in Sprague-Dawley rats showed that heroin self-administration led to hypomethylation of the GABRD gene and transcriptional upregulation in the NAc. Manipulations with DNMT inhibitor and MET affected heroin-seeking behavior, possibly through direct repression of DNMT1 and DNMT3A expression to alter the DNA methylation landscape of the GABRD gene.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Neurosciences
Ashley L. Holloway, Michael D. Schaid, Talia N. Lerner
Summary: Major depressive disorder (MDD) is a leading cause of disability worldwide, characterized by decreased motivation and deficits in reward processing. Chronic dysregulation of the HPA axis is associated with MDD, but the mechanisms linking cortisol to behavioral deficits may differ by sex.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Psychology, Multidisciplinary
Samantha M. Wilfur, Elizabeth C. McNeely, Aliya A. Lackan, Cassie P. Bowers, Kah-Chung Leong
Summary: Alcohol use disorder is a public health concern, especially for females who are susceptible to stress-induced relapse. Research on pharmacological interventions for female stress-induced ethanol reinstatement is limited. This study investigates the effectiveness of oxytocin in attenuating yohimbine-induced reinstatement of ethanol-seeking in female rats. The findings highlight oxytocin's potential therapeutic effect in female stress-induced alcohol relapse and its modulation by the central amygdala.
BEHAVIORAL SCIENCES
(2023)
Article
Neurosciences
Jessica M. Illenberger, Francisco J. Flores-Ramirez, Glenn Pascasio, Alessandra Matzeu, Remi Martin-Fardon
Summary: Chronic opioid use disrupts circadian rhythm and sleep, which can lead to increased opioid use and relapse. Dual orexin receptor antagonists (DORAs), developed for insomnia treatment, are found to alleviate withdrawal-associated sleep disturbances. This study aimed to investigate the effect of DORA-12, a newly developed DORA, on physiological activity disturbances during oxycodone abstinence and its potential role in preventing oxycodone-seeking behavior.
Article
Medicine, Research & Experimental
Fateme Khodabande, Esmaeil Akbari, Motahareh Rouhi Ardeshiri
Summary: The orexin 1 receptors in the dorsal raphe nucleus play a significant role in the consolidation of spatial reference memory in rats, while the orexin 2 receptors do not have an effect.
Article
Neurosciences
Aleksandra Trenk, Magdalena Walczak, Agata Szlaga, Kamil Pradel, Anna Blasiak, Tomasz Blasiak
Summary: Theta oscillations play a key role in memory formation, sensorimotor integration, and control of locomotion and behavioral states. This study investigated the generation and synchronization of theta oscillations in the brain, particularly focusing on the interactions between brain nuclei and the medial septum (MS). The researchers discovered distinct populations of neurons in the pontine nucleus incertus (NI) that fire action potentials in different manners and have different connections with the MS. These findings provide insights into the mechanisms of theta rhythm generation and transmission in the brain.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Anna Gugula, Aleksandra Trenk, Aleksandra Celary, Katarzyna Cizio, Grzegorz Tylko, Anna Blasiak, Grzegorz Hess
Summary: Early-life stress has long-term consequences, including an increased risk for drug abuse and psychiatric disorders later in life, higher in women than in men. This study reveals the changes in stress sensitivity of specific neuronal populations in the ventral tegmental area and lateral hypothalamus caused by early-life stress.
Article
Neurosciences
Agata Szlaga, Patryk Sambak, Aleksandra Trenk, Anna Gugula, Caitlin E. Singleton, Gniewosz Drwiega, Tomasz Blasiak, Sherie Ma, Andrew L. Gundlach, Anna Blasiak
Summary: This study provides a comprehensive characterization of the neural connections between the medial septum (MS) and nucleus incertus (NI) in the rat. The findings reveal a discrete NI neuronal network with specific electrophysiological and neurochemical features that control the MS. These data are important for understanding the neuronal mechanisms underlying the septohippocampal system and related behaviors.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Cell Biology
Monika Bijata, Ewa Baczynska, Franziska E. Mueller, Krystian Bijata, Julia Masternak, Adam Krzystyniak, Bernadeta Szewczyk, Marcin Siwiec, Svitlana Antoniuk, Matylda Roszkowska, Izabela Figiel, Marta Magnowska, Krzysztof H. Olszynski, Agnieszka D. Wardak, Adam Hogendorf, Blazej Ruszczycki, Nataliya Gorinski, Josephine Labus, Tomasz Stepien, Sylwia Tarka, Andrzej J. Bojarski, Krzysztof Tokarski, Robert K. Filipkowski, Evgeni Ponimaskin, Jakub Wlodarczyk
Summary: This study investigates the impact of 5-HT7R/MMP-9 signaling and dendritic spine plasticity on major depressive disorder. The results show that activation of 5-HT7R and chronic stress both negatively affect dendritic spine elongation and density in the hippocampus, which are associated with depressive-like behavior.
Article
Neurosciences
Agata Szlaga, Patryk Sambak, Anna Gugula, Aleksandra Trenk, Andrew L. Gundlach, Anna Blasiak
Summary: The nucleus incertus (NI) is a brainstem structure involved in the control of arousal, stress responses, and locomotor activity. This study found that NI neurons express dopamine type 2 (D2) receptors and receive strong catecholaminergic innervation. Activation of D2 receptors in the NI had excitatory and inhibitory effects on neuronal activity, which were cell-type specific. These findings highlight the importance of the NI in integrating arousal-related neuronal information.
Review
Neurosciences
Anna Blasiak, Anna Gugula, Andrew L. L. Gundlach, Francisco E. E. Olucha-Bordonau, Francesco Aniello, Aldo Donizetti
Summary: This review investigates the evolutionary conservation of relaxin family peptide and receptor gene expression and their role in brain neural circuits. The use of zebrafish as a model organism provides a potential advantage in exploring the diversification and conservation of relaxin family ligands and receptor systems.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Tomasz Kowalczyk, Agata Staszelis, Renata Bocian, Marcin Siwiec, Joanna E. Sowa, Krzysztof Tokarski, Paulina Kazmierska-Grebowska, Bartosz Caban
Summary: The posterior hypothalamic area (PHa) is an important part of the ascending brainstem hippocampal synchronizing pathway, which regulates rhythmic theta activity. In addition to its role in modulation of limbic theta activity, the PHa can also generate well-synchronized local theta field potentials by itself. Glutamatergic stimulation of PHa induces theta field oscillations in both the supramammillary and posterior hypothalamic nuclei, and these oscillations are accompanied by the activity of specific subtypes of theta-related neurons.
Review
Pharmacology & Pharmacy
Leigh C. Walker, Kade L. Huckstep, Howard C. Becker, Christopher J. Langmead, Andrew J. Lawrence
Summary: Emerging evidence suggests muscarinic acetylcholine receptors are potential targets for treating alcohol use disorder. This review integrates findings from medicinal chemistry, molecular biology, addiction, and learning/cognition fields to explore the potential of muscarinic receptor ligands in treating cognitive dysfunction, motivation to consume alcohol, and relapse associated with alcohol use disorder. The dysfunctional role of cholinergic system in alcohol use disorder is discussed, along with the potential therapeutic targets of specific muscarinic receptors, particularly M-4 and M-5 receptors. The use of subtype-selective allosteric modulators is proposed as a strategy to target these receptors, and the potential repurposing of muscarinic receptor modulators for alcohol use disorder is highlighted.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Endocrinology & Metabolism
Duan Chen, Jens F. Rehfeld, Alan G. Watts, Patrik Rorsman, Andrew L. Gundlach
Summary: In the 20th Century, regulatory peptide discovery advanced from identification to extraction, isolation, and cloning, leading to the elucidation of systems physiology and the approval of improved therapeutics and diagnostics. This wealth of information calls for a renaissance in regulatory peptides, as reviewed in this article, which focuses on gut peptides, stress hormone, and relaxin-family peptides and receptors, aiming to enhance our understanding of the current state-of-the-art and future priorities.
JOURNAL OF NEUROENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Mai Iwasaki, Arthur Lefevre, Ferdinand Althammer, Etienne Clauss Creusot, Olga Lapies, Hugues Petitjean, Louis Hilfiger, Damien Kerspern, Meggane Melchior, Stephanie Kueppers, Quirin Krabichler, Ryan Patwell, Alan Kania, Tim Gruber, Matthew K. Kirchner, Moritz Wimmer, Henning Froehlich, Laura Doetsch, Jonas Schimmer, Sabine C. Herpertz, Beate Ditzen, Christian P. Schaaf, Kai Schoenig, Dusan Bartsch, Anna Gugula, Aleksandra Trenk, Anna Blasiak, Javier E. Stern, Pascal Darbon, Valery Grinevich, Alexandre Charlet
Summary: The hypothalamic neuropeptide oxytocin activates oxytocin-receptor expressing GABA neurons in the periaqueductal grey, reducing pain-like behaviors in rats. The discovery of this analgesic pathway provides insight into the analgesic effects of oxytocin.
NATURE COMMUNICATIONS
(2023)
Article
Neurosciences
Francisco Ros-Bernal, Isis Gil-Miravet, Jorge Luceron, Monica Navarro-Sanchez, Esther Castillo-Gomez, Andrew L. Gundlach, Francisco E. Olucha-Bordonau
Summary: This study investigated the neurodevelopmental consequences of RLN3 innervation in the septal area during postnatal development in rats. The results showed that RLN3 network development in the septal area began between P17 and P20 and was correlated with the onset of hippocampal theta rhythm and associated learning processes.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Ross A. D. Bathgate, Praveen Praveen, Ashish Sethi, Werner I. Furuya, Rishi R. Dhingra, Martina Kocan, Qinghao Ou, Adam L. Valkovic, Isis Gil-Miravet, Moinica Navarro-Sanchez, Francisco E. Olucha-Bordonau, Andrew L. Gundlach, K. Johan Rosengren, Paul R. Gooley, Mathias Dutschmann, Mohammed Akhter Hossain
Summary: Researchers have developed a novel noncovalent stapling strategy using an unnatural amino acid called & alpha;-methyl-l-phenylalanine (& alpha;F) to stabilize peptides. They successfully created a peptide mimetic of human relaxin-3 (H3 relaxin) with high stability and biological function similar to H3 relaxin. This peptide mimetic, H3B10-27(13/17 & alpha;F), holds great potential as a drug lead and as a tool for studying the physiological functions of RXFP3.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Anatomy & Morphology
Isis Gil-Miravet, Angel Nunez-Molina, Monica Navarro-Sanchez, Esther Castillo-Gomez, Francisco Ros-Bernal, Andrew L. Gundlach, Francisco E. Olucha-Bordonau
Summary: Nucleus incertus (NI) neurons in the pontine tegmentum give rise to ascending forebrain projections and express the neuropeptide relaxin-3 (RLN3) which acts via the relaxin-family peptide 3 receptor (RXFP3). The medial septum (MS) can drive activity in the hippocampus and entorhinal cortex, and the NI projects to these centers. In vivo studies showed that electrical stimulation of the NI induced theta activity in the MS and the entorhinal cortex, which was impaired by an RXFP3 antagonist.
BRAIN STRUCTURE & FUNCTION
(2023)
Correction
Neurosciences
Lucia Privitera, Ellen L. Hogg, Matthias Gaestel, Mark J. Wall, Sonia A. L. Correa
Article
Neurosciences
Li-Ya Jiang, Guan-Hao Wang, Jing-Jiao Xu, Xiao-Li Li, Xiao-Yan Lin, Xiang Fang, Hong-Xu Zhang, Mei Feng, Chun-Ming Jiang
Summary: This study reveals the importance of LINC00473 in regulating temozolomide (TMZ) resistance in glioblastoma (GB) and its potential mechanism. By regulating the expression of CEBP alpha and MGMT, LINC00473 promotes the formation of chemoresistance. Furthermore, LINC00473 can transfer chemoresistance to adjacent sensitive cells through exosomes.
Article
Neurosciences
Olga Kopach, Tetyana Pivneva, Nataliya Fedirko, Nana Voitenko
Summary: This study found that diabetic animals exhibit severe xerostomia characterized by reduced saliva flow rate, diminished total protein content, and decreased amylase activity. The impaired saliva production in diabetes is associated with reduced and delayed intracellular Ca2+ signals in submandibular acinar cells, caused by malfunctioning mitochondria. Targeting malfunctioning mitochondria may be a potential strategy for the treatment of diabetic xerostomia.
Article
Neurosciences
Nicholas M. Timme, Cherish E. Ardinger, Seth D. C. Weir, Rachel Zelaya-Escobar, Rachel Kruger, Christopher C. Lapish
Summary: This study aimed to assess aversion-resistant drinking behavior in head-fixed mice and explore the relationship between non-consummatory behaviors and aversion-resistant drinking. The results showed that head-fixed mice exhibited heterogenous levels of aversion-resistant drinking and non-consummatory behaviors were related to the intensity of this behavior.
Article
Neurosciences
David R. Maguire, Charles P. France
Summary: Methocinnamox (MCAM) is a novel, long-acting opioid receptor antagonist that effectively decreases fentanyl self-administration and prevents opioid overdose in monkeys. The study demonstrates the potential therapeutic utility of MCAM in the treatment of opioid use disorder.
Article
Neurosciences
Xiang Li, Dan Feng, Shenglu Ma, Mingxing Li, Shulei Zhao, Man Tang
Summary: This study investigated the effects of fluoxetine on neurochemical, neurobiological, and neurobehavioral changes in different subregions of the hippocampus. The results showed that fluoxetine increased dialysate 5-HT, decreased membrane 5-HTT protein, and increased cytoplasmic fraction. Additionally, fluoxetine reduced immobility times in behavioral tests, with greater effects observed in the ventral subregion compared to the dorsal subregion.
Article
Neurosciences
Alexander V. Zholos, Mariia I. Melnyk, Dariia O. Dryn
Summary: Acetylcholine is an important neurotransmitter in visceral smooth muscles, activating M2 and M3 muscarinic receptors to cause smooth muscle excitation and contraction. This review focuses on the cellular and molecular mechanisms underlying acetylcholine-induced depolarisation and smooth muscle contraction, as well as the effects of anticholinergic drugs on gastrointestinal motility. The knowledge gained from recent studies has greatly expanded our understanding of these processes.
Article
Neurosciences
Zhenlong Li, Hsien-Yu Peng, Chau-Shoun Lee, Tzer-Bin Lin, Ming-Chun Hsieh, Cheng-Yuan Lai, Han-Fang Wu, Lih-Chyang Chen, Mei-Ci Chen, Dylan Chou
Summary: Methylone shows significant efficacy in treating depression and social deficits, making it an ideal candidate for anti-depressant medication.
Article
Neurosciences
Aline Freyssin, Allison Carles, Sarra Guehairia, Gilles Rubinstenn, Tangui Maurice
Summary: This study explores the potential of combining FENM and S1R agonists in the treatment of Alzheimer's disease. The results showed that most FENM-based combinations can protect against learning deficits caused by A beta 25-35, with better efficacy in short-term memory.
Article
Neurosciences
J. D. Lorente, J. Cuitavi, L. Rullo, S. Candeletti, P. Romualdi, L. Hipolito
Summary: This study analyzed the effects of pain on negative affect in different sexes and time courses, as well as the involvement of the dynorphinergic and corticotropin releasing factor systems in these pain-related behaviors. The results showed sex and time-dependent anxiety- and anhedonia-like behaviors induced by pain in female rats. The recruitment of KOR/DYN in the NAc was identified as a key neurological substrate mediating pain-induced behavioral alterations.
Article
Neurosciences
Rongjun Liu, Daofan Sun, Xiuzhong Xing, Qingge Chen, Bo Lu, Bo Meng, Hui Yuan, Lan Mo, Liufang Sheng, Jinwei Zheng, Qiusheng Wang, Junping Chen, Xiaowei Chen
Summary: The coexistence of pain and depression is frequently observed in patients with chronic pain and depression. Oxytocin, a neuropeptide, has been reported to relieve chronic pain and depressive symptoms. This study investigated the effect of intranasal oxytocin on neuropathic pain and comorbid depressive symptoms, and found that oxytocin attenuated depression-like behavior but did not alleviate mechanical hyperalgesia. The results suggest that intranasal oxytocin may have the potential to treat depressive symptoms in neuropathic pain patients.
