Article
Biochemistry & Molecular Biology
Alla B. Arefieva, Polina D. Komleva, Vladimir S. Naumenko, Nikita V. Khotskin, Alexander V. Kulikov
Summary: This study investigated the effects of the pharmacological chaperone BH4 on the mutant TPH2 enzyme. The results showed that although BH4 demonstrated chaperone effects in vitro, it was unable to increase the activity of mutant TPH2 in vivo.
Article
Biochemistry & Molecular Biology
Alexander Mordhorst, Priyavathi Dhandapani, Susann Matthes, Valentina Mosienko, Michael Rothe, Mihail Todiras, Julie Self, Wolf-Hagen Schunck, Anja Schutz, Michael Bader, Natalia Alenina
Summary: Serotonin synthesis involves the hydroxylation of tryptophan, with most vertebrates having two known enzymes for this step. However, even in animals lacking these two enzymes, there is still some serotonin production, suggesting the presence of a third enzyme. The study found evidence that phenylalanine hydroxylase (PAH) may act as a third tryptophan hydroxylase in mammals, contributing to serotonin levels in the blood and potentially serving as a local source of serotonin in organs where other TPHs are not expressed.
Article
Clinical Neurology
Tatyana Strekalova, Evgeniy Svirin, Jonas Waider, Anna Gorlova, Raymond Cespuglio, Allan Kalueff, Igor Pomytkin, Angelika G. Schmitt-Boehrer, Klaus-Peter Lesch, Daniel C. Anthony
Summary: Gene-environment interaction determines vulnerability to stress-related neuropsychiatric disorders, with Tph2 gene variants linked to increased impulsivity and aggression. Tph2+/- mice exhibit increased aggression, reduced sociability, and altered brain metabolism of serotonin, dopamine, and norepinephrine after predator stress exposure, showing resilience to stress. This study highlights how GxE interaction studies can reveal genetically determined predispositions and uncover latent behaviors.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Polyna D. Komleva, Ghofran Alhalabi, Arseniy E. Izyurov, Nikita V. Khotskin, Alexander V. Kulikov
Summary: This study investigates the effects of the TPH2 and Raly-Agouti gene mutations on body mass, behavior, and the 5-HT and melanocortin systems in the brain of mice. The mutations increase TPH2 enzyme activity and Agouti gene expression, but have no effect on 5-HT and 5-HIAA levels or the expression of other genes. The mutations have different effects on weight gain and depressive-like behavior, and when combined, cause hind limb dystonia in mice.
Article
Behavioral Sciences
Zhang-Lin Liu, Xin-Qiang Wang, Ming-fan Liu, Bao-juan Ye
Summary: The TPH2 gene polymorphisms are associated with depression, with significant results in Chinese subjects. Further biological experiments are needed to understand the effects of different SNPs on depression.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2022)
Article
Medicine, Research & Experimental
P. D. Komleva, E. Yu. Bazhenova, N. V. Khotskin, E. A. Kulikova, A. V. Kulikov
Summary: The study examined the effect of the C1473G polymorphism in the Tph2 gene on motor activity and serotonin levels in the brain. It was found that this polymorphism influenced the level of 5-HIAA in the cortex and striatum. This finding is important for understanding the role of tryptophan hydroxylase 2 in the nervous system's adaptation during infections and for predicting and reducing the risks of mental disorders.
BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE
(2022)
Article
Parasitology
Michaela Herz, Klaus Brehm
Summary: The study reveals the important role of serotonin in E. multilocularis development and proliferation, with evidence that serotonin is crucial for parasite integrity and survival. Serotonin also stimulates parasite metacestode development and proliferation, potentially contributing to parasite formation and growth in the liver.
PARASITES & VECTORS
(2021)
Article
Endocrinology & Metabolism
Zhenya Zhu, Xiaolong Chen, Shuang Chen, Chenmin Hu, Rui Guo, Yuhao Wu, Ziyu Liu, Xiaoli Shu, Mizu Jiang
Summary: In this study, the effects of GsMTx4 on 5-HT secretion in QGP-1 cells were explored. It was found that GsMTx4 increased 5-HT levels in QGP-1 cells and affected the expression of Piezo1/2 ion channels, TPH1 enzyme, and p38 signaling pathway. GsMTx4 also influenced mouse intestinal motility and blocked the response of QGP-1 cells to ultrasound.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
D. V. Sherbakov, A. B. Arefieva, P. D. Komleva, A. E. Iz'urov, N. V. Khotskin, D. V. Bazovkina, A. V. Kulikov
Summary: The aim of this study was to investigate the mRNA distribution of TPH1 and TPH2 genes in brain structures under normal conditions and after inflammation. Saline or lipopolysaccharide (LPS) was administered to mice, and markers of inflammation and serotonin levels were assessed. The results showed significant changes in spleen and thymus mass, as well as alterations in serotonin levels and TPH activity in different brain regions. The expression of Tph1 gene was found to be low and did not significantly affect serotonin synthesis in the mouse brain.
Article
Clinical Neurology
Congcong Liu, Keshuang Li, Meina Fu, Yingying Zhang, Cornelia Sindermann, Christian Montag, Xiaoxiao Zheng, Hongxing Zhang, Shuxia Yao, Zheng Wang, Bo Zhou, Keith M. Kendrick, Benjamin Becker
Summary: Serotonin plays a crucial role in emotion regulation and can contribute to the development and treatment of emotional dysregulations. A recent study found that individual variations in the TPH2 genetics may increase susceptibility to the detrimental effects of temporary decreases in 5-HT signaling, leading to increased anxiety and altered neural threat reactivity.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Valentina S. Evsiukova, Alla B. Arefieva, Ivan E. Sorokin, Alexander V. Kulikov
Summary: This study investigated the levels of serotonin and its main metabolite, 5-hydroxyindoleacetic acid, as well as the activities of the key enzymes involved in their synthesis and degradation in the brains of male and female turquoise killifish at different ages. The results showed that age had a significant effect on body mass, serotonin level, and enzyme activities in the killifish brain. The level of serotonin decreased with age, and there were age-related alterations in the activities of tryptophan hydroxylases and monoamine oxidase. These findings highlight the suitability of N. furzeri as a model organism for studying age-related changes in the serotonin system in the brain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Giulia Sbrini, Sabrina I. Hanswijk, Paola Brivio, Anthonieke Middelman, Michael Bader, Fabio Fumagalli, Natalia Alenina, Judith R. Homberg, Francesca Calabrese
Summary: Peripheral serotonin levels have an influence on brain functions under basal and dynamic situations. The lack of peripheral serotonin can reduce anxiety-like behavior, as well as neuronal activation and the expression of brain plasticity-related genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Tatyana Strekalova, Oleg Moskvin, Aayushi Y. Jain, Nikita Gorbunov, Anna Gorlova, Daria Sadovnik, Aleksei Umriukhin, Raymond Cespuglio, Wing Shan Yu, Anna Chung Kwan Tse, Allan V. Kalueff, Klaus-Peter Lesch, Lee Wei Lim
Summary: This study revealed that mice with partial genetic inactivation of Tph2 exhibit excessive aggression under stress. Transcriptomic analysis identified molecular markers related to neurodevelopmental deficits and emotional dysregulation. The findings highlight the interplay between Tph2 inactivation and severe stress experience in mediating female aggression.
JOURNAL OF NEURAL TRANSMISSION
(2023)
Article
Multidisciplinary Sciences
Atae Akhrif, Marcel Romanos, Katharina Peters, Ann-Kathrin Furtmann, Julian Caspers, Klaus-Peter Lesch, Eva M. Meisenzahl-Lechner, Susanne Neufang
Summary: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that often persists into adulthood. In this study, the interaction of genetic and environmental factors in causing ADHD symptoms, such as impulsivity, was investigated. The TPH2 gene and DNA methylation in the 5' untranslated region of TPH2 were found to be associated with brain activity and behavioral performance in ADHD patients. This study provides insights into how genetic and epigenetic factors contribute to ADHD and impulsivity.
Article
Psychiatry
Nuo Chen, Ming Zhao, Yaxin Guo, Nan Wu, Baihui Cao, Bing Zhan, Tian Zhou, Yubin Li, Faliang Zhu, Wanjun Chen, Yan Li, Lining Zhang
Summary: The lack of ACSS2 impairs BDNF-dependent synaptic plasticity and TPH2-mediated serotonin generation, leading to depressive-like behavior. D-mannose, an ACSS2 inducer, shows rapid and long-lasting antidepressant-like effects. ACSS2 promotes TPH2 histone acetylation and transcription through AMPK activation. D-mannose activates AMPK to increase nuclear ACSS2 levels, facilitating fast-acting and persistent antidepressant responses. ACSS2 and D-mannose may be potential targets and therapeutic agents for resisting depression.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Psychology, Developmental
Berit Skretting Solberg, Jan Haavik, Anne Halmoy
JOURNAL OF ATTENTION DISORDERS
(2019)
Review
Psychology, Developmental
Johanne Telnes Instanes, Kari Klungsoyr, Anne Halmoy, Ole Bernt Fasmer, Jan Haavik
JOURNAL OF ATTENTION DISORDERS
(2018)
Article
Neurosciences
Berit S. Solberg, Tetyana Zayats, Maj-Britt Posserud, Anne Halmoy, Anders Engeland, Jan Haavik, Kari Klungsoyr
BIOLOGICAL PSYCHIATRY
(2019)
Article
Behavioral Sciences
Erlend Joramo Brevik, Astri J. Lundervold, Jan Haavik, Maj-Britt Posserud
BRAIN AND BEHAVIOR
(2020)
Article
Nutrition & Dietetics
Lizanne J. S. Schweren, Henrik Larsson, Petra C. Vinke, Lin Li, Liv Grimstvedt Kvalvik, Alejandro Arias-Vasquez, Jan Haavik, Catharina A. Hartman
Summary: High stress and high neuroticism scores were weakly associated with poorer diet quality, but poor diet quality did not predict mental health problems. Overall diet quality did not mediate the relationship between stress/neuroticism and common mental health problems.
CLINICAL NUTRITION
(2021)
Article
Chemistry, Medicinal
Nibal Betari, Kristoffer Sahlholm, Yuta Ishizuka, Knut Teigen, Jan Haavik
FUTURE MEDICINAL CHEMISTRY
(2020)
Review
Behavioral Sciences
Carmen Schiweck, Gara Arteaga-Henriquez, Mareike Aichholzer, Sharmili Edwin Thanarajah, Sebastian Vargas-Caceres, Silke Matura, Oliver Grimm, Jan Haavik, Sarah Kittel-Schneider, Josep Antoni Ramos-Quiroga, Stephen Faraone, Andreas Reif
Summary: ADHD and BD have a high degree of comorbidity in adults, with substantial heterogeneity in comorbidity rates. Patients with comorbid ADHD tend to have an earlier onset of BD. Cultural, geographical, and methodological differences should be considered for evaluating diagnostic criteria to prevent misdiagnosis and provide optimal care for both disorders.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Nutrition & Dietetics
Lizanne J. S. Schweren, Daan van Rooij, Huiqing Shi, Henrik Larsson, Alejandro Arias-Vasquez, Lin Li, Liv Grimstvedt Kvalvik, Jan Haavik, Jan Buitelaar, Catharina Hartman
Summary: Disinhibition is closely related to dietary habits among middle-aged/older adults, but the effects are very weak, and no association with MVPA was found.
Article
Chemistry, Medicinal
Nibal Betari, Knut Teigen, Kristoffer Sahlholm, Jan Haavik
Summary: The study found that beclomethasone dipropionate can act as a stabilizer of TPHs, with pharmacological effects, and may inspire further development of steroid scaffolds as potential antidepressant drugs.
FUTURE MEDICINAL CHEMISTRY
(2021)
Review
Behavioral Sciences
Selina Cannon Homaei, Helene Barone, Rune Kleppe, Nibal Betari, Andreas Reif, Jan Haavik
Summary: Neurometabolic diseases (NMDs), caused by genetic abnormalities, can interfere with the normal development and function of the nervous system. Many NMDs are associated with neuropsychiatric manifestations, including symptoms of ADHD, and share similar neurochemical mechanisms with ADHD. Understanding these relationships can have important therapeutic implications.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2022)
Article
Psychiatry
Giuseppe Fanelli, Barbara Franke, Ward De Witte, I. Hyun Ruisch, Jan Haavik, Veerle van Gils, Willemijn J. Jansen, Stephanie J. B. Vos, Lars Lind, Jan K. Buitelaar, Tobias Banaschewski, Soren Dalsgaard, Alessandro Serretti, Nina Roth Mota, Geert Poelmans, Janita Bralten
Summary: The prevalence of somatic insulinopathies, such as metabolic syndrome, obesity, and type 2 diabetes mellitus, is higher in Alzheimer's disease, autism spectrum disorder, and obsessive-compulsive disorder. There is a genetic overlap between these neuropsychiatric disorders and insulin-related diseases/traits, indicating a potential shared genetic mechanism.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Genetics & Heredity
Lin Li, Mark J. Taylor, Katarina Baelter, Tian Xie, Berit Skretting Solberg, Jan Haavik, Alejandro Arias Vasquez, Catharina A. Hartman, Henrik Larsson
Summary: This study found that genetic factors play a more prominent role in ADHD symptoms in individuals with higher consumption of sugar and unhealthy foods.
Review
Health Care Sciences & Services
Gyrid Nygaard, Peter D. Szigetvari, Ann Kari Grindheim, Peter Ruoff, Aurora Martinez, Jan Haavik, Rune Kleppe, Marte Flydal
Summary: Dopa-responsive dystonia (DRD) is a rare movement disorder linked to defective dopamine synthesis, mainly associated with mutations in the GCH1 gene. However, some patients do not respond well to L-DOPA treatment, especially in severe cases of TH deficiency. This highlights the need for more effective and personalized treatment options.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Chemistry, Medicinal
Tore Ivar Malmei Aarsland, Johanne Telnes Instanes, Maj-Britt Rocio Posserud, Arve Ulvik, Ute Kessler, Jan Haavik
Summary: This study systematically reviewed the changes in tryptophan metabolism and kynurenine levels after electroconvulsive therapy (ECT) and assessed methodological issues. The results showed no evidence of an effect of ECT on any outcome variable. Future studies should consider larger sample sizes, important covariates, and variability within and between subjects.
Article
Biochemistry & Molecular Biology
Peter D. Szigetvari, Sudarshan Patil, Even Birkeland, Rune Kleppe, Jan Haavik
Summary: This study investigates the effects of phenylketonuria and tyrosinemia type 1 on dopamine synthesis by exposing dopamine-producing cell lines to phenylalanine and tyrosine. The results show that high levels of phenylalanine and low or high levels of tyrosine decrease cellular dopamine levels and alter related proteins and processes. A mathematical model is developed to predict how external aromatic amino acids can affect dopamine synthesis in cells.
NEUROCHEMISTRY INTERNATIONAL
(2023)