Article
Psychiatry
Anissa Abi-Dargham, Jonathan A. Javitch, Mark Slifstein, Alan Anticevic, Monica E. Calkins, Youngsun T. Cho, Clara Fonteneau, Roberto Gil, Ragy Girgis, Raquel E. Gur, Ruben C. Gur, Jack Grinband, Joshua Kantrowitz, Christian Kohler, John Krystal, John Murray, Mohini Ranganathan, Nicole Santamauro, Jared Van Snellenberg, Zailyn Tamayo, Daniel Wolf, David Gray, Jeffrey Lieberman
Summary: Decades of research have shown the importance of optimal stimulation of cortical dopaminergic receptors, particularly the D1R receptor, for prefrontal-mediated cognition. Challenges in developing D1R targeting drugs include determining the optimal level of D1R stimulation and the unknown mechanism for stimulation, which could include partial or full agonism, biased agonism, or allosteric modulation. Previous drugs targeting D1R have faced issues like poor bioavailability and insufficient target engagement at tolerable doses, but newer drugs like CVL-562 offer potential solutions if carefully tested.
SCHIZOPHRENIA BULLETIN
(2022)
Article
Neurosciences
Alice Servonnet, Florence Allain, Alice Gravel-Chouinard, Giovanni Hernandez, Casey Bourdeau Caporuscio, Mathilde Legrix, Daniel Levesque, Pierre-Paul Rompre, Anne-Noel Samaha
Summary: Antipsychotic treatment can induce dopamine supersensitivity in rats, leading to an enhanced response to D-amphetamine. After cessation of treatment, rats exhibit a supersensitive psychomotor response to the D2 agonist quinpirole, while D1 agonists and a dopamine reuptake blocker do not have the same effect.
Article
Pharmacology & Pharmacy
Francesca Manago, Diego Scheggia, Maria Pontillo, Maddalena Mereu, Rosa Mastrogiacomo, Gayatri Udayan, Paola Valentini, Maria Cristina Tata, Daniel R. Weinberger, Cynthia S. Weickert, Pier Paolo Pompa, Maria A. De Luca, Stefano Vicari, Francesco Papaleo
Summary: This study discovered a genetic interaction between the Comt and Dtnbp1 genes, which modulate dopaminergic signaling in the brain and lead to specific cognitive disturbances. The researchers also developed an easy and inexpensive genetic screening kit for clinical application.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Clinical Neurology
Kate M. Witt, David N. Harper, Bart A. Ellenbroek
Summary: This study reveals the modulating role of dopamine D1 receptors in effort-based decision-making and highlights the sex * genotype interaction. These findings are important for the treatment of neuropsychiatric disorders and future research considering sex differences.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Chuan-Ching Lai, Rathinasamy Baskaran, Chih-Yu Tsao, Li-Heng Tuan, Pei-Fen Siow, Mahalakshmi Palani, Lukas Jyuhn-Hsiarn Lee, Chih-Min Liu, Hai-Gwo Hwu, Li-Jen Lee
Summary: Schizophrenia usually manifests during adolescence to young adulthood, providing an opportunity for early intervention. This study investigated the preventive effect of chronic N-acetylcysteine (NAC) treatment on the outbreak of psychosis in Disc1 Het mice and found that NAC can normalize biochemical and morphological features in the striatum. The findings not only support the use of NAC as a dietary supplement for schizophrenia prodromes, but also contribute to our understanding of potential therapeutic targets for treating mental disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Daniel C. Javitt
Summary: Cognitive impairment is a prominent feature of schizophrenia, and its assessment methods are well established. The role of social cognitive impairment and sensory-level dysfunction in functional outcomes has also been recognized. Treatment development targeting N-methyl-d-aspartate receptor (NMDAR) and its associated impairments has become encouraging. Mismatch negativity has emerged as a promising biomarker for early-stage drug development in schizophrenia.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2023)
Article
Pharmacology & Pharmacy
Gabriela Tavares, Fatima O. Martins, Bernardete F. Melo, Paulo Matafome, Silvia Conde
Summary: Peripheral dopamine plays a role in regulating glucose uptake in insulin-sensitive tissues, with dopamine receptors having differential involvement. Dopamine also affects lipid metabolism in white adipose tissue. The modulation of the dopaminergic system in the periphery could be a potential therapeutic approach for metabolic disorders.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chenhao Li, Yang Li, Wenwen Zhang, Zhenjie Ma, Shaobo Xiao, Wei Xie, Shuai Miao, Bozhi Li, Guangshuang Lu, Yingyuan Liu, Wenhao Bai, Shengyuan Yu
Summary: Clinical imaging studies have shown that the hypothalamus is activated in migraine patients before and during headache, and has increased functional connectivity with the spinal trigeminal nucleus. The dopaminergic system in the hypothalamus, particularly the A11 nucleus, may play a crucial role in the pathogenesis of migraine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Kyna-Anne Conn, Simin Zou, Joyosmita Das, Suzy Alexander, Thomas H. J. Burne, James P. Kesby
Summary: In this study, the cognitive symptoms of schizophrenia, including impaired goal-directed action, were found to be associated with altered dopamine signaling in the brain. The differential roles of the dorsomedial and ventral inputs into the striatum in goal-directed action were identified, providing insights into the cognitive problems in schizophrenia.
Article
Biochemistry & Molecular Biology
Yi Zhang, Huan Gui, Zikun Duan, Tian Yu, Jie Zhang, Xiaoli Liang, Chengxi Liu
Summary: Systemic activation of D1 receptors has been found to promote emergence from propofol-induced unconsciousness, with the nucleus accumbens (NAc) showing disinhibited neuronal activity during the recovery phase. D1 receptor modulation on the activity of NAc MSNs plays a vital role in facilitating the emergence from propofol-induced unconsciousness, as shown by whole-cell patch clamp recordings and pharmacological intervention experiments.
NEUROCHEMICAL RESEARCH
(2021)
Article
Plant Sciences
Han Zhou, Tao Hou, Zhenhua Gao, Xiujie Guo, Chaoran Wang, Jixia Wang, Yanfang Liu, Xinmiao Liang
Summary: This study isolated eight alkaloids from lotus leaves and evaluated them on dopamine receptors. These alkaloids acted as antagonists for D1 and D2 receptors, with O-nornuciferine being the most potent among the eight on both receptors.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Neurosciences
Baoyu Shen, Dongxian Zhang, Xiaofeng Zeng, Lina Guan, Genmeng Yang, Liu Liu, Jian Huang, Yuanyuan Li, Shijun Hong, Lihua Li
Summary: This study reveals that METH induces DA release via the DRD1-MeCP2-BDNF-TrkB signaling pathway, and CBD significantly inhibits DA release induced by METH through modulation of this pathway.
PSYCHOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jing Yu, Jiabing Zhu, Jian Deng, Jing Shen, Fukuan Du, Xu Wu, Yu Chen, Mingxing Li, Qinglian Wen, Zhangang Xiao, Yueshui Zhao
Summary: The study demonstrates that activation of DRD1 signaling can promote lipolysis and browning of adipocytes, reducing adipocyte size and increasing the release of fatty acids, providing new strategies for obesity treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Behavioral Sciences
Alan Jung Park
Summary: Novelty enhances the ability of mice to overcome established behavioral bias and adapt to new rules by impacting connectivity within the VTA-HPC-mPFC circuit. Blocking dopamine D1-receptors in the vHPC abolishes the effects of novelty.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2023)
Article
Psychology, Biological
G. Horvath, G. Adam, G. Tuboly, G. Kekesi, A. Buki, E. Ducza, E. Szucs, S. Benyhe, G. Benedek
Summary: The study reveals that caffeine has disparate effects on behavioral parameters in both healthy and schizophrenia-like animals, with prolonged changes in the dopaminergic system.
PHYSIOLOGY & BEHAVIOR
(2021)
Article
Clinical Neurology
Ling Shan, Rawien Balesar, Dick F. Swaab, Gert Jan Lammers, Rolf Fronczek
Summary: The study discovered that narcolepsy type 1 leads to the loss of hypocretin neurons in the hypothalamus, while sparing other neuronal populations. This selective decrease in hypocretin neurons provides novel targets for diagnostics and therapeutic interventions.
ANNALS OF NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Mandy L. Ballinger, Swetansu Pattnaik, Piyushkumar A. Mundra, Milita Zaheed, Emma Rath, Peter Priestley, Jonathan Baber, Isabelle Ray-Coquard, Nicholas Isambert, Sylvain Causeret, Winette T. A. van der Graaf, Ajay Puri, Florence Duffaud, Axel Le Cesne, Beatrice Seddon, Coonoor Chandrasekar, Joshua D. Schiffman, Andrew S. Brohl, Paul A. James, Jean-Emmanuel Kurtz, Nicolas Penel, Ola Myklebost, Leonardo A. Meza-Zepeda, Hilda Pickett, Maya Kansara, Nicola Waddell, Olga Kondrashova, John Pearson, Andrew P. Barbour, Shuai Li, Tuong L. Nguyen, Diane Fatkin, Robert M. Graham, Eleni Giannoulatou, Melissa J. Green, Warren Kaplan, Shyamsundar Ravishankar, Joseph Copty, Joseph E. Powell, Edwin Cuppen, Kristel van Eijk, Jan Veldink, Jin-Hee Ahn, Jeong Eun Kim, R. Lor Randall, Kathy Tucker, Ian Judson, Rajiv Sarin, Thomas Ludwig, Emmanuelle Genin, Jean-Francois Deleuze, Michelle Haber, Glenn Marshall, Murray J. Cairns, Jean-Yves Blay, David M. Thomas
Summary: Cancer genetics has focused on epithelial malignancies, but this study explores specific pathways related to sarcomas, rare malignancies derived from embryonic mesoderm. Germline sequencing of sporadic cases and healthy controls reveals two sarcoma-specific pathways involved in mitotic and telomere functions. Centrosome gene variants are linked to specific tumors, while heritable defects in the shelterin complex increase susceptibility to sarcomas, melanomas, and thyroid cancers. These findings highlight the role of heritable defects in mitotic and telomere biology in sarcoma risk.
Article
Medicine, Research & Experimental
Wesley S. van de Geer, Ron H. J. Mathijssen, Job van Riet, Neeltje Steeghs, Mariette Labots, Carla van Herpen, Lot A. Devriese, Vivianne C. G. Tjan-Heijnen, Emile E. Voest, Stefan Sleijfer, John W. M. Martens, Edwin Cuppen, Harmen J. G. van de Werken, Sander Bins
Summary: Drug resistance is a persistent problem in cancer therapy, and alterations in drug transport over the cancer cell membrane can contribute to resistance. This study analyzed the mutational landscape of transporter genes in cancer patients who had received different systemic therapies, and identified potential stressor mechanisms that may be involved in drug resistance.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Engineering, Civil
Xufeng Cui, Jing Zhang, Wei Huang, Cuicui Liu, Ling Shan, Yuehua Jiang
Summary: In this paper, the spatial distribution of the life service industry in Wuhan was studied using kernel density analysis, entropy index, and standard deviational ellipse methods. The results show that the industry displays a distribution of coexistence of single and multiple centers, with the centers located in Wuchang and Jianghan. Except for transportation, the other six types of the industry show a trend of development toward the southeast. This study provides important information for the spatial planning of the life service industry in polycentric cities.
JOURNAL OF URBAN PLANNING AND DEVELOPMENT
(2023)
Article
Multidisciplinary Sciences
Francisco Martinez-Jimenez, Ali Movasati, Sascha Remy Brunner, Luan Nguyen, Peter Priestley, Edwin Cuppen, Arne Van Hoeck
Summary: This study characterizes the genomic differences between early-stage untreated primary tumors and late-stage treated metastatic tumors. Metastatic tumors have lower heterogeneity and a conserved karyotype, with only a modest increase in mutations. Most cancer types show either moderate or consistent genomic differences between early-stage and late-stage disease, except for breast, prostate, thyroid, kidney renal clear cell carcinomas, and pancreatic neuroendocrine tumors, which exhibit extensive genetic landscape transformation in advanced stages.
Article
Genetics & Heredity
Francisco Martinez-Jimenez, Peter Priestley, Charles Shale, Jonathan Baber, Erik Rozemuller, Edwin Cuppen
Summary: A pan-cancer analysis reveals the diversity of genetic immune escape mechanisms in primary and metastatic tumors, while a new tool called LILAC is presented for characterizing the HLA-I locus. The study found that one in four tumors have GIE alterations, with variability across cancer types. GIE prevalence is generally consistent between primary and metastatic tumors, and the loss of heterozygosity of HLA-I allele presents a large neoepitope repertoire.
Article
Multidisciplinary Sciences
Hongjie Bao, Xiaoqian Liu, Xiaoyong Xu, Ling Shan, Yongteng Ma, Xiaoshuang Qu, Xiangyu He
Summary: Measuring regional differences in agricultural green total factor productivity (AGTFP) provides a basis for policy guidance on agricultural green development in the Yangtze River Delta (YRD) region. This study used a two-period Malmquist-Luenberger index under the carbon emission constraint to measure the AGTFP of cities in the YRD region from 2001 to 2019. The results showed an increasing trend in AGTFP in the region, with different drivers of growth in the eastern and southern cities.
Article
Multidisciplinary Sciences
Ali Seifinejad, Mergim Ramosaj, Ling Shan, Sha Li, Marie-Laure Possovre, Corinne Pfister, Rolf Fronczek, Lee A. Garrett-Sinha, David Frieser, Makoto Honda, Yoan Arribat, Dogan Grepper, Francesca Amati, Marie Picot, Andrea Agnoletto, Christian Iseli, Nicolas Chartrel, Roland Liblau, Gert J. Lammers, Anne Vassalli, Mehdi Tafti
Summary: Narcolepsy with cataplexy is caused by deficiency in the neuropeptide hypocretin/orexin (HCRT), believed to result from autoimmune destruction of hypocretin-producing neurons. Loss of hypothalamic CRH-producing neurons suggests that mechanisms other than autoimmune attack are involved. HCRT, PDYN, and CRH are epigenetically silenced by hypothalamic inflammation in narcolepsy patients, without concurrent cell death. Methylation reversal may lead to a potential cure for narcolepsy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Nicolle Besselink, Janneke Keijer, Carlo Vermeulen, Sander Boymans, Jeroen de Ridder, Arne van Hoeck, Edwin Cuppen, Ewart Kuijk
Summary: DNA methylation plays a crucial role in cell identity and genomic stability. Cancer is associated with global loss of DNA methylation, leading to cell transformation and genomic instability. However, the precise mutational consequences of global hypomethylation have not been fully assessed.
SCIENTIFIC REPORTS
(2023)
Article
Biology
Casper J. H. Wolf, Hanka Venselaar, Marcia Spoelder, Harmen Beurmanjer, Arnt F. A. Schellekens, Judith R. Homberg
Summary: The neurotransmitter GHB is involved in neuronal energy homeostasis and is also used recreationally and medicinally. Little is known about the structure and function of GHB receptor subtypes. This opinion article discusses the potential structural and functional properties of the GHBh1 receptor subtype, which shares similarities with a riboflavin transporter and may have dual functions. Further research into the GHBh1 receptor subtype could lead to new therapeutic possibilities for GHB.
Article
Clinical Neurology
Ling Shan, Suzan Linssen, Zoe Harteman, Fleur den Dekker, Lamis Shuker, Rawien Balesar, Nicole Breesuwsma, Jasper Anink, Jingru Zhou, Gert Jan Lammers, Dick F. F. Swaab, Rolf Fronczek
Summary: The study found that NT1 patients have a significant reduction in CRH-positive neurons in the PVN and an increase in the percentage of CRH cells co-expressing AVP. There is also evidence of enhanced activity in histamine neurons and unchanged density of TH-positive LC neurons in NT1. These findings suggest upregulation of histamine and CRH neurons in NT1.
ANNALS OF NEUROLOGY
(2023)
Article
Neurosciences
Jocelien D. A. Olivier, Josien A. Janssen, Diana C. Esquivel-Franco, Stephen de Pretre, Berend Olivier
Summary: This study investigated the acute inhibitory effects of the combination of Atlas987 and paroxetine, called Enduro, on male rat sexual behavior. The results showed that Enduro acutely reduced the number of ejaculations and increased ejaculation latencies in a dose-dependent manner. These findings suggest that Enduro may be a therapeutically attractive on-demand treatment for lifelong premature ejaculation in men.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Oncology
Lindsay Angus, Marcel Smid, Saskia M. Wilting, Manouk K. Bos, Neeltje Steeghs, Inge R. H. M. Konings, Vivianne C. G. Tjan-Heijnen, Johanna M. G. H. van Riel, Agnes J. van de Wouw, Edwin Cuppen, Martijn P. Lolkema, Agnes Jager, Stefan Sleijfer, John W. M. Martens
Summary: This study investigated the mutated genes and mutation patterns, as well as the expression levels of relevant genes, in 101 breast cancer metastatic lesions with ER-positive tumors. The analyses revealed two distinct patient groups, one showing ongoing, active ER and its associated signal route, and the other showing lower ER expression levels. The study highlights the importance of combining mutation and expression analyses to identify patients who may still benefit from anti-hormonal treatment targeting ER.
Article
Multidisciplinary Sciences
Di Dai, Qian Qin, Xinyu Zhu, Qiuyuan Fang, Xianzong Meng, Lin Bai, Guang Yang, Ling Shan, Chunqing Liu
Summary: The detection of neurotransmitters has been widely used to study neuropsychiatric diseases. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has advantages in determining neurotransmitter levels. However, there are still challenges in neurotransmitter detection. Our lab has developed a rapid and sensitive HPLC-MS/MS protocol that can simultaneously detect 5 neurotransmitters with an easy pretreatment procedure. The protocol provides reference values for the lab using an Agilent HPLC-MS/MS system with a triple quadrupole analyzer.
Meeting Abstract
Oncology
Daniel Vis, Sander Palit, Marie Corradi, Martijn Lolkema, Niven Mehra, Edwin Cuppen, Lodewyk F. A. Wessels, Rene Bernards, Wilbert Zwart, Michiel S. van der Heijden, Andries M. Bergman