Article
Neurosciences
Jamie L. Scholl, Rajeshwari R. Solanki, Michael J. Watt, Kenneth J. Renner, Gina L. Forster
Summary: In rats, withdrawal from chronic amphetamine increases OCT3 expression in specific brain regions, and corticosterone can increase OCT3 expression in the ventral hippocampus independently of glucocorticoid receptors (GRs). Mifepristone, a GR antagonist, does not block the effects of corticosterone on OCT3 expression and anxiety-like behavior.
Article
Biochemistry & Molecular Biology
David A. Doetsch, Salim Ansari, Ole Jensen, Lukas Gebauer, Christof Duecker, Jurgen Brockmoeller, Alexandra Sachkova
Summary: This study characterized the substrate spectrum of a proton-organic cation (H + OC) antiporter, which is responsible for transporting organic cations through membranes. Using hCMEC/D3 cells as a model, the researchers examined the uptake of 72 drugs and identified 37 of them as good substrates of the H + OC antiporter. Further analysis showed that the substrates had specific characteristics, such as being more hydrophobic and having a lower topological polar surface area.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Alexandra Sachkova, Ole Jensen, Christof Duecker, Salim Ansari, Juergen Brockmoeller
Summary: About 30% of small molecular drugs are organic cations that require membrane transporters to pass through biological membranes. The proton-organic cation antiporter, known as H+ OC antiporter, may have a significant role in the transport of organic cations through the blood-brain barrier. However, the gene coding for this antiporter has not yet been identified. This review summarizes the functional characteristics, expression, and substrate spectrum of the H+ OC antiporter.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Medicine, Research & Experimental
Johanna Vollmar, Yong Ook Kim, Jens Uwe Marquardt, Peter R. Galle, Detlef Schuppan, Tim Zimmermann
Summary: Organic cation transporters OCT have been found to play a crucial role in the uptake and detoxification of various substances. The study revealed that loss of Oct3 can enhance hepatocarcinogenesis and fibrosis, with associated changes in HNF4α expression. Additionally, differences in HNF4α expression were also observed in Oct3 knockout mice with cholestasis and fibrosis.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Kyra-Elisa Maria Redeker, Ole Jensen, Lukas Gebauer, Marleen Julia Meyer-Toennies, Juergen Brockmoeller
Summary: The human organic cation transporter 1 (OCT1) plays a crucial role in hepatic uptake of organic cations. Recent studies suggest that OCT1 can also transport neutral and anionic substrates, but with lower activity. Understanding the substrate spectrum and transport mechanisms of OCT1, including organic anions, is essential for a comprehensive understanding of its clinical relevance.
Article
Pharmacology & Pharmacy
Alexandra Sachkova, David Alexander Doetsch, Ole Jensen, Juergen Brockmoeller, Salim Ansari
Summary: The study found that all the psychostimulants studied, except for mescaline, were substrates of the H+/OC antiporter, emphasizing the need for a better characterization of this transport protein.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiaohong Zhang, Stephen H. Wright
Summary: In this study, the turnover rates (TORs) of MATE1 and OCT2 proteins expressed in CHO cells were determined using a quantitative western blot method. The results showed that MATE1 and OCT2 proteins represented 25% and 24%, respectively, of the total expression on the cell surface. The calculated TOR values for MATE1 and OCT2 were consistent with values determined for other transporters.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Stanislava Bukatova, Emese Renczes, Alexandra Reichova, Johan Filo, Anna Sadlonova, Boris Mravec, Daniela Ostatnikova, Jan Bakos, Zuzana Bacova
Summary: The study found an imbalance between excitation and inhibition in the brain of Shank3 deficient mice, especially during early development and adulthood, which may lead to behavioral abnormalities.
NEUROCHEMICAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Ole Jensen, Johannes Matthaei, Henry G. Klemp, Marleen J. Meyer, Jurgen Brockmoller, Mladen V. Tzvetkov
Summary: This study confirmed IBC as an endogenous biomarker of OCT1 activity in humans, with OCT1 potentially regulating cellular concentrations of specific regulators or co-substrates in lipid and energy metabolism. Unlike in mice, OCT1 in humans may not directly mediate the efflux of IBC, suggesting a different mechanism for the association between blood concentrations of carnitine derivatives and OCT1 genotype in humans.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Sandra Schorn, Ann-Kristin Dicke, Ute Neugebauer, Rita Schroter, Maren Friedrich, Stefan Reuter, Giuliano Ciarimboli
Summary: The study showed that organic cation transporter 2 (OCT2) is expressed in the pancreas and has a functional relationship with glucose transporter 2 (GLUT2). High glucose was found to stimulate OCT2 expression and activity, while overexpression of GLUT2 decreased OCT2 activity. This suggests a complex regulatory relationship between OCT2, GLUT2, and glucose levels in the pancreas.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Ole Jensen, Muhammad Rafehi, Lukas Gebauer, Jurgen Brockmoeller
Summary: Psychostimulants and hallucinogens have been found to be substrates of OCTs, with genetic polymorphisms in OCT1 playing a significant role in the cellular uptake of mescaline.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Johannes Matthaei, Juergen Brockmoeller, Werner Steimer, Konstanze Pischa, Stefan Leucht, Maria Kullmann, Ole Jensen, Typhaine Ouethy, Mladen Vassilev Tzvetkov, Muhammad Rafehi
Summary: The pharmacokinetics of the tricyclic antidepressant amitriptyline is primarily influenced by the genotypes of CYP2D6 and CYP2C19, with OCT1 genetic variation playing a minor role. Inhibition of OCT1 by amitriptyline and nortriptyline in vitro was observed, but significant effects of OCT1 genetic polymorphism on drug pharmacokinetics were not found in clinical studies with healthy volunteers and depressive disorder patients.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Minghao Chen, Guoquan You, Cong Xie, Ruopeng Yang, Wanyu Hu, Zhijie Zheng, Shuwen Liu, Ling Ye
Summary: The study reveals that the bioavailability of metformin is significantly reduced in CIA rats, which may be related to the up-regulation of renal protein OCT2 function.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Neurosciences
Jinan Li, Chang Liu, Samuel Kaefer, Mariam Youssef, Bo Zhao
Summary: Studies have shown that genetically disrupting mechanotransduction in mice partially protects hair cells from cisplatin-induced hair cell death, and functional mechanotransduction is required for the uptake of cisplatin in murine hair cells. Additionally, the otoprotective effects of cimetidine do not require mechanotransduction, suggesting that both the mechanotransduction channel and the organic cation transporter are critical for cisplatin ototoxicity in murine hair cells.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Saliha Harrach, Jasmin Haag, Martin Steinbuechel, Rita Schroeter, Ute Neugebauer, Jessica Bertrand, Giuliano Ciarimboli
Summary: The study found that Masitinib interacts with various OCTs, particularly OCT1 and hOCT2, to effectively transport across cell membranes. There are important differences in the interaction between mouse and human OCTs. Further research is needed to understand the in vitro and in vivo properties of Masitinib and its uptake mechanisms related to transporters, in order to contribute to successful and responsible therapy employment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Alejandro Orrico-Sanchez, Laetitia Chausset-Boissarie, Rodolphe Alves de Sousa, Basile Coutens, Sara Rezai Amin, Vincent Vialou, Franck Louis, Assia Hessani, Patrick M. Dansette, Teodoro Zornoza, Carole Gruszczynski, Bruno Giros, Bruno P. Guiard, Francine Acher, Nicolas Pietrancosta, Sophie Gautron
MOLECULAR PSYCHIATRY
(2020)
Article
Neurosciences
Odile Poirel, Lauren E. Mamer, Melissa A. Herman, Marie Arnulf-Kempcke, Myriam Kervern, Brigitte Potier, Stephanie Miot, Jing Wang, Franck-Cyril Favre-Besse, Isabelle Brabet, Younes Laras, Hugues-Olivier Bertrand, Francine Acher, Jean-Philippe Pin, Jean-Luc Puel, Bruno Giros, Jacques Epelbaum, Christian Rosenmund, Patrick Dutar, Stephanie Daumas, Salah El Mestikawy, Nicolas Pietrancosta
Article
Biochemistry & Molecular Biology
Laura Cutando, Emma Puighermanal, Laia Castell, Pauline Tarot, Federica Bertaso, Patricia Bonnavion, Alban de Kerchove d'Exaerde, Elsa Isingrini, Micaela Galante, Glenn Dallerac, Vincent Pascoli, Christian Luescher, Bruno Giros, Emmanuel Valjent
Summary: The study found that d-amphetamine and methylphenidate can increase phosphorylation of GluA1 in the membrane fraction of the mouse cerebellum; Bergmann glial cells are the source of pS845-GluA1 and intact NE release is required; NE regulates GluA1 phosphorylation in Bergmann glial cells in response to prescription stimulants.
Article
Neurosciences
Sanjeev K. Bhardwaj, Qiming Cui, Luc Moquin, Alain Gratton, Bruno Giros, Lalit K. Srivastava
Summary: Reduced expression of schizophrenia-associated gene DTNBP1 and its protein product dysbindin-1 in the brains of schizophrenia patients has been reported. Mouse models with DTNBP1 knockout show altered dopaminergic, glutamatergic, and GABAergic neurotransmission in cortico-limbic regions. Dysbindin-1 deficiency in dopamine neurons leads to impaired mesolimbic dopamine transmission, affecting locomotor behavior and prepulse inhibition.
Article
Neurosciences
Elise Morice, Valerie Enderlin, Sophie Gautron, Serge Laroche
Summary: The mitogen-activated protein kinases (MAPK) play a crucial role in memory consolidation, with MSK1 and MSK2 mediating signal transduction downstream of MAPK. While loss of Msk1 affects synaptic transmission and spatial recognition memory, the deletion of Msk2 does not impact these aspects. However, neither Msk1 nor Msk2 deletion affects LTP in vivo, as well as LTP-induced phosphorylation of CREB and expression of EGR1.
Article
Neurosciences
Cuong Pham, Karine Herault, Martin Oheim, Steeve Maldera, Vincent Vialou, Bruno Cauli, Dongdong Li
Summary: This study investigated astrocytic responses to the neurotoxic A beta fragment present in Alzheimer's disease patients through fluorescence imaging of signaling pathways. The results showed that A beta 25-35 induced different Ca2+ responses in astrocytes in different states, accompanied by a multiphasic release of signaling molecules.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Editorial Material
Neurosciences
Sophie Gautron
BIOLOGICAL PSYCHIATRY
(2021)
Article
Neurosciences
Florian Rebeillard, Stephanie De Gois, Nicolas Pietrancosta, Thi Hue Mai, Rene Lai-Kuen, Brigitte L. Kieffer, Bruno Giros, Renaud Massart, Michele Darmon, Jorge Diaz
Summary: GPR88 is highly expressed in striatal medium spiny neurons and has an atypical intranuclear localization in cortical neurons. It interacts with nuclear proteins ATRX, TOP2B, and BAZ2B involved in chromatin remodeling.
Article
Neurosciences
Amaia Nunez-delMoral, Iria Brocos-Mosquera, Vincent Vialou, Luis F. Callado, Amaia M. Erdozain
Summary: This study characterized the expression of hevin protein in adult human brain by Western blot, revealing specific immunoreactive bands with different glycosylation patterns. The study also found differences in hevin expression in various brain regions and its presence in certain diseases and physiological fluids.
Editorial Material
Medicine, Research & Experimental
Vincent Vialou
M S-MEDECINE SCIENCES
(2022)
Article
Neurosciences
Francesco Petrelli, Tamara Zehnder, Anthony Laugeray, Sarah Mondoloni, Corrado Cali, Luca Pucci, Alicia Molinero Perez, Bianca Maria Bondiolotti, Eva De Oliveira Figueiredo, Glenn Dallerac, Nicole Deglon, Bruno Giros, Lorenzo Magrassi, Jean-Pierre Mothet, Manuel Mameli, Linda D. Simmler, Paola Bezzi
Summary: This study investigates the relationship between VMAT2 in astrocytes and the regulation of DA levels, finding that impairment of astrocytic control of DA leads to reduced DA levels, excessive grooming, and compulsive repetitive behaviors. The expression of VMAT2 in human PFC astrocytes validates the translational relevance of these findings.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Amaia Nunez-delMoral, Paula C. Bianchi, Iria Brocos-Mosquera, Augusto Anesio, Paola Palombo, Rosana Camarini, Fabio C. Cruz, Luis F. Callado, Vincent Vialou, Amaia M. Erdozain
Summary: A protein called hevin is highly expressed in the adult brain and plays a role in stress resilience and motivated behaviors. This study found that hevin levels are elevated in the brain tissue of individuals with alcohol use disorder, and that alcohol exposure and withdrawal can alter hevin levels. Moreover, suppressing hevin expression in a specific brain region leads to increased alcohol consumption.
Article
Multidisciplinary Sciences
Jill Rocchetti, Caroline Fasano, Gregory Dal-Bo, Elisa Guma, Salah El Mestikawy, Tak-Pan Wong, Gohar Fakhfouri, Bruno Giros
Summary: Evidence suggests that excessive dopamine affects cognitive function in schizophrenia and antipsychotic drugs fail to improve cognitive deficits. Blocking D2 dopamine receptors leads to reshaping of mesohippocampal fibers, synaptic transmission deficits, and impairments in learning and memory. It is currently unknown how excessive dopamine affects hippocampal-related cognitive functions and the impact of antipsychotic drugs on hippocampal functions in this state.
Article
Psychiatry
Alejandro Orrico-Sanchez, Bruno P. Guiard, Stella Manta, Jacques Callebert, Jean-Marie Launay, Franck Louis, Antoine Paccard, Carole Gruszczynski, Catalina Betancur, Vincent Vialou, Sophie Gautron
Summary: This study provides the first evidence of the physiological relevance of OCT2-mediated tryptophan transport and its biological consequences on serotonin homeostasis in the brain and SSRI efficacy.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)