TY - JOUR AU - Price, N.L. AU - Fernández-Tussy, P. AU - Varela, L. AU - Cardelo, M.P. AU - Shanabrough, M. AU - Aryal, B. AU - de, Cabo R. AU - Suárez, Y. AU - Horváth, Tamás AU - Fernández-Hernando, C. TI - microRNA-33 controls hunger signaling in hypothalamic AgRP neurons JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 15 PY - 2024 IS - 1 SN - 2041-1723 DO - 10.1038/s41467-024-46427-0 UR - https://m2.mtmt.hu/api/publication/34766210 ID - 34766210 N1 - Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, United States Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, United States Yale Center for Molecular and System Metabolism. Yale University School of Medicine, New Haven, CT, United States Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, United States Laboratory of Glia -Neuron Interactions in the control of Hunger. Achucarro Basque Center for Neuroscience, Vizcaya, Leioa, 48940, Spain IKERBASQUE, Basque Foundation for Science, Vizcaya, Bilbao, 48009, Spain Department of Pathology. Yale University School of Medicine, New Haven, CT, United States Department of Neuroscience. Yale University School of Medicine, New Haven, CT, United States Export Date: 3 April 2024 Correspondence Address: Fernández-Hernando, C.; Vascular Biology and Therapeutics Program, United States; email: carlos.fernandez@yale.edu Correspondence Address: Horvath, T.L.; Department of Comparative Medicine, United States; email: tamas.horvath@yale.edu Chemicals/CAS: Agouti-Related Protein; MicroRNAs; Mirn33 microRNA, mouse Funding details: National Institutes of Health, NIH, 1K01DK120794, AG067329, DA046160, DK045735, DK120891, DK126447, R35HL135820, R35HL155988 Funding details: American Heart Association, AHA, 20TPA35490416, 23CDA1055007, 874771 Funding details: Klarman Family Foundation, KFF Funding details: Ministerio de Ciencia e Innovación, MCIN Funding details: Agencia Estatal de Investigación, AEI, PID2021-125193OA-I00 Funding text 1: This work was at least in part supported by grants from the National Institutes of Health (R35HL135820 to CF-H; and R35HL155988 to YS; 1K01DK120794 to NP; and DK120891, DA046160, DK045735, AG067329 and DK126447 to TLH), the American Heart Association (20TPA35490416 to CF-H; and 874771 and 23CDA1055007 to PF-T), the Klarman Family Foundation to TLH and Plan Generación Conocimiento from the Spanish Ministry of Science and Innovation and Agencia Estatal de Investigación (PID2021-125193OA-I00 to LV). Schemes in Figs. , and and Supplementary Figs. 2a and d and 3a and f were generated using BioRender.com. AB - AgRP neurons drive hunger, and excessive nutrient intake is the primary driver of obesity and associated metabolic disorders. While many factors impacting central regulation of feeding behavior have been established, the role of microRNAs in this process is poorly understood. Utilizing unique mouse models, we demonstrate that miR-33 plays a critical role in the regulation of AgRP neurons, and that loss of miR-33 leads to increased feeding, obesity, and metabolic dysfunction in mice. These effects include the regulation of multiple miR-33 target genes involved in mitochondrial biogenesis and fatty acid metabolism. Our findings elucidate a key regulatory pathway regulated by a non-coding RNA that impacts hunger by controlling multiple bioenergetic processes associated with the activation of AgRP neurons, providing alternative therapeutic approaches to modulate feeding behavior and associated metabolic diseases. © The Author(s) 2024. LA - English DB - MTMT ER - TY - JOUR AU - Stutz, Bernardo AU - Waterson, Michael AU - Sestan-Pesa, Matija AU - Dietrich, Marcelo AU - Skarica, Mario AU - Sestan, Nenad AU - Rácz, Bence AU - Magyar, Aletta AU - Sótonyi, Péter AU - Liu, Zhong-Wu AU - Gao, Xiao-Bing AU - Matyas, Ferenc AU - Stoiljkovic, Milan AU - Horváth, Tamás TI - Hunger-promoting hypothalamic AgRP neurons control structure and function of the medial prefrontal cortex JF - JOURNAL OF NEUROCHEMISTRY J2 - J NEUROCHEM VL - 166 PY - 2023 SP - 138 EP - 139 PG - 2 SN - 0022-3042 UR - https://m2.mtmt.hu/api/publication/34221294 ID - 34221294 N1 - Supplement: 1 LA - English DB - MTMT ER - TY - JOUR AU - Sestan-Pesa, Matija AU - Shanabrough, Marya AU - Horváth, Tamás AU - Miletta, Maria Consolata TI - Impaired Ghrelin Signaling Does Not Lead to Alterations of Anxiety-like Behaviors in Adult Mice Chronically Exposed to THC during Adolescence JF - BIOMEDICINES J2 - BIOMEDICINES VL - 11 PY - 2023 IS - 1 PG - 13 SN - 2227-9059 DO - 10.3390/biomedicines11010144 UR - https://m2.mtmt.hu/api/publication/33912086 ID - 33912086 AB - As marijuana use during adolescence has been increasing, the need to understand the effects of its long-term use becomes crucial. Previous research suggested that marijuana consumption during adolescence increases the risk of developing mental illnesses, such as schizophrenia, depression, and anxiety. Ghrelin is a peptide produced primarily in the gut and is important for feeding behavior. Recent studies have shown that ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR), play important roles in mediating stress, as well as anxiety and depression-like behaviors in animal models. Here, we investigated the effects of chronic tetrahydrocannabinol (THC) administration during late adolescence (P42-55) in GHSR (GHSR (-/-)) knockout mice and their wild-type littermates in relation to anxiety-like behaviors. We determined that continuous THC exposure during late adolescence did not lead to any significant alterations in the anxiety-like behaviors of adult mice, regardless of genotype, following a prolonged period of no exposure (1 month). These data indicate that in the presence of intact or impaired ghrelin/GHSR signaling, THC exposure during late adolescence has limited if any long-term impact on anxiety-like behaviors in mice. LA - English DB - MTMT ER - TY - JOUR AU - Stevens, Hanna E. AU - Scuderi, Soraya AU - Collica, Sarah C. AU - Tomasi, Simone AU - Horváth, Tamás AU - Vaccarino, Flora M. TI - Neonatal loss of FGFR2 in astroglial cells affects locomotion, sociability, working memory, and glia-neuron interactions in mice JF - TRANSLATIONAL PSYCHIATRY J2 - TRANSL PSYCHIAT VL - 13 PY - 2023 IS - 1 PG - 13 SN - 2158-3188 DO - 10.1038/s41398-023-02372-y UR - https://m2.mtmt.hu/api/publication/33859437 ID - 33859437 N1 - Child Study Center, Yale School of Medicine, New Haven, CT 06520, United States Department of Psychiatry, Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52246, United States Department of Neuroscience, Yale University, New Haven, CT 06520, United States Department of Comparative Medicine, Department of Obstetrics and Gynecology, Yale School of Medicine, New Haven, CT 06520, United States Export Date: 21 December 2023 Correspondence Address: Stevens, H.E.; Child Study Center, United States; email: hanna-stevens@uiowa.edu Chemicals/CAS: glutamate ammonia ligase, 9023-70-5; tamoxifen, 10540-29-1; Receptor, Fibroblast Growth Factor, Type 2 Funding details: Roy J. Carver Charitable Trust, RJCCT, R01 MH067715 Funding details: University of Iowa, UI Funding text 1: This work was supported by the Roy J. Carver Charitable Trust (HES), National Institute of Mental Health R01 MH067715 (FMV), International PhD program in Neuropharmacology at the University of Catania Medical School, Italy (SS), and Ida P. Haller Chair in Child and Adolescent Psychiatry at the University of Iowa (HES). We thank Robert J. Taylor for mouse management and testing. AB - Fibroblast growth factor receptor 2 (FGFR2) is almost exclusively expressed in glial cells in postnatal mouse brain, but its impact in glia for brain behavioral functioning is poorly understood. We compared behavioral effects from FGFR2 loss in both neurons and astroglial cells and from FGFR2 loss in astroglial cells by using either the pluripotent progenitor-driven hGFAP-cre or the tamoxifen-inducible astrocyte-driven GFAP-creER(T2) in Fgfr2 floxed mice. When FGFR2 was eliminated in embryonic pluripotent precursors or in early postnatal astroglia, mice were hyperactive, and had small changes in working memory, sociability, and anxiety-like behavior. In contrast, FGFR2 loss in astrocytes starting at 8 weeks of age resulted only in reduced anxiety-like behavior. Therefore, early postnatal loss of FGFR2 in astroglia is critical for broad behavioral dysregulation. Neurobiological assessments demonstrated that astrocyte-neuron membrane contact was reduced and glial glutamine synthetase expression increased only by early postnatal FGFR2 loss. We conclude that altered astroglial cell function dependent on FGFR2 in the early postnatal period may result in impaired synaptic development and behavioral regulation, modeling childhood behavioral deficits like attention deficit hyperactivity disorder (ADHD). LA - English DB - MTMT ER - TY - JOUR AU - Ralevski, Alexandra AU - Apelt, Federico AU - Olas, Justyna J. AU - Mueller-Roeber, Bernd AU - Rugarli, Elena I. AU - Kragler, Friedrich AU - Horváth, Tamás TI - Plant mitochondrial FMT and its mammalian homolog CLUH controls development and behavior in Arabidopsis and locomotion in mice JF - CELLULAR AND MOLECULAR LIFE SCIENCES J2 - CELL MOL LIFE SCI VL - 79 PY - 2022 IS - 6 SN - 1420-682X DO - 10.1007/s00018-022-04382-3 UR - https://m2.mtmt.hu/api/publication/34855345 ID - 34855345 LA - English DB - MTMT ER - TY - JOUR AU - Wang, Qi AU - Zhang, Bichen AU - Stutz, Bernardo AU - Liu, Zhong-Wu AU - Horváth, Tamás AU - Yang, Xiaoyong TI - Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity JF - SCIENCE ADVANCES J2 - SCI ADV VL - 8 PY - 2022 IS - 35 PG - 13 SN - 2375-2548 DO - 10.1126/sciadv.abn8092 UR - https://m2.mtmt.hu/api/publication/33911811 ID - 33911811 AB - The ventromedial hypothalamus (VMH) is known to regulate body weight and counterregulatory response. However, how VMH neurons regulate lipid metabolism and energy balance remains unknown. O-linked beta-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. Here, we report that genetic ablation of OGT in VMH neurons inhibits neuronal excitability. Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. The obesity phenotype is associated with adipocyte hypertrophy and reduced lipolysis of white adipose tissues. In addition, OGT deletion in VMH neurons down-regulates the sympathetic activity and impairs the sympathetic innervation of white adipose tissues. These findings identify OGT in the VMH as a homeostatic set point that controls body weight and underscore the importance of the VMH in regulating lipid metabolism through white adipose tissue-specific innervation. LA - English DB - MTMT ER - TY - BOOK AU - Horváth, Tamás AU - Hirsch, J. AU - Molnár, Z. TI - Body, Brain, Behavior: Three Views and a Conversation PB - Elsevier CY - Amsterdam PY - 2022 SP - 1 EP - 415 SP - 415 SN - 9780128180938 DO - 10.1016/B978-0-12-818093-8.00032-X UR - https://m2.mtmt.hu/api/publication/33880969 ID - 33880969 N1 - Departments of Comparative Medicine, Neuroscience and Ob/Gyn, Yale University School of Medicine, New Haven, CT, United States Department of Anatomy and Histology, University of Veterinary Medicine, Budapest, Hungary Departments of Comparative Medicine, Psychiatry and Neuroscience, Yale University School of Medicine, New haven, CT, United States Department Medical Physics and Biomedical Engineering, University College London, United Kingdom Department of Physiology, Anatomy and Genetics, Oxford Martin School, St John’s College, University of Oxford, Oxford, United Kingdom Charité-Universitätsmedizin Berlin, Berlin, Germany Acibadem Mehmet Ali Aydinlar Üniversitesi, Istanbul, Turkey Cited By :3 Export Date: 26 May 2023 AB - Body, Brain, Behavior: Three Views and a Conversation describes brain research on the frontiers, with a particular emphasis on the relationship between the brain and its development and evolution, peripheral organs, and other brains in communication. The book expands current views of neuroscience by illustrating the integration of these disciplines. By using a novel method of conversations between 3 scientists of different disciplines, cellular, endocrine, developmental, and social processes are seamlessly woven into topics that relate to contemporary living in health and disease. This book is a critical read for anyone who wants to become familiar with the inner workings of the nervous system and its intimate connections to the universe of contemporary life issues. © 2022 Elsevier Inc. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Stutz, Bernardo AU - Waterson, Michael J. AU - Šestan-Peša, Matija AU - Dietrich, Marcelo O. AU - Škarica, Mario AU - Sestan, Nenad AU - Rácz, Bence AU - Magyar, Aletta AU - Sótonyi, Péter AU - Liu, Zhong-Wu AU - Gao, Xiao-Bing AU - Mátyás, Ferenc AU - Stoiljkovic, Milan AU - Horváth, Tamás TI - AgRP neurons control structure and function of the medial prefrontal cortex JF - MOLECULAR PSYCHIATRY J2 - MOL PSYCHIATR VL - 27 PY - 2022 SP - 3951 EP - 3960 PG - 10 SN - 1359-4184 DO - 10.1038/s41380-022-01691-8 UR - https://m2.mtmt.hu/api/publication/33035643 ID - 33035643 LA - English DB - MTMT ER - TY - JOUR AU - Endle, Heiko AU - Horta, Guilherme AU - Stutz, Bernardo AU - Muthuraman, Muthuraman AU - Tegeder, Irmgard AU - Schreiber, Yannick AU - Snodgrass, Isabel Faria AU - Gurke, Robert AU - Liu, Zhong-Wu AU - Sestan-Pesa, Matija AU - Radyushkin, Konstantin AU - Streu, Nora AU - Fan, Wei AU - Baumgart, Jan AU - Li, Yan AU - Kloss, Florian AU - Groppa, Sergiu AU - Opel, Nils AU - Dannlowski, Udo AU - Grabe, Hans J. AU - Zipp, Frauke AU - Rácz, Bence AU - Horváth, Tamás AU - Nitsch, Robert AU - Vogt, Johannes TI - AgRP neurons control feeding behaviour at cortical synapses via peripherally derived lysophospholipids JF - NATURE METABOLISM J2 - NAT METAB VL - 4 PY - 2022 IS - 6 SP - 683 EP - 692 PG - 10 SN - 2522-5812 DO - 10.1038/s42255-022-00589-7 UR - https://m2.mtmt.hu/api/publication/32909442 ID - 32909442 AB - Phospholipid levels are influenced by peripheral metabolism. Within the central nervous system, synaptic phospholipids regulate glutamatergic transmission and cortical excitability. Whether changes in peripheral metabolism affect brain lipid levels and cortical excitability remains unknown. Here, we show that levels of lysophosphatidic acid (LPA) species in the blood and cerebrospinal fluid are elevated after overnight fasting and lead to higher cortical excitability. LPA-related cortical excitability increases fasting-induced hyperphagia, and is decreased following inhibition of LPA synthesis. Mice expressing a human mutation (Prg-1R346T) leading to higher synaptic lipid-mediated cortical excitability display increased fasting-induced hyperphagia. Accordingly, human subjects with this mutation have higher body mass index and prevalence of type 2 diabetes. We further show that the effects of LPA following fasting are under the control of hypothalamic agouti-related peptide (AgRP) neurons. Depletion of AgRP-expressing cells in adult mice decreases fasting-induced elevation of circulating LPAs, as well as cortical excitability, while blunting hyperphagia. These findings reveal a direct influence of circulating LPAs under the control of hypothalamic AgRP neurons on cortical excitability, unmasking an alternative non-neuronal route by which the hypothalamus can exert a robust impact on the cortex and thereby affect food intake. LA - English DB - MTMT ER - TY - JOUR AU - Gao, Xiao-Bing AU - Horváth, Tamás TI - From Molecule to Behavior: Hypocretin/orexin Revisited From a Sex-dependent Perspective JF - ENDOCRINE REVIEWS J2 - ENDOCR REV PY - 2021 PG - 18 SN - 0163-769X DO - 10.1210/endrev/bnab042 UR - https://m2.mtmt.hu/api/publication/32881945 ID - 32881945 N1 - Export Date: 19 October 2022 CODEN: ERVID Correspondence Address: Gao, X.-B.; Departments of Comparative Medicine, United States; email: xiao-bing.gao@yale.edu Correspondence Address: Horvath, T.L.; Departments of Comparative Medicine, United States; email: tamas.horvath@yale.edu Chemicals/CAS: Intracellular Signaling Peptides and Proteins; Neuropeptides; Orexins Funding details: National Institutes of Health, NIH, DA046160, DK120891 Funding text 1: The authors’ studies have been supported by National Institutes of Health grants DA046160 (T.L.H. and X.B.G.) and DK120891 (X.B.G. and T.L.H.). AB - The hypocretin/orexin (Hcrt/Orx) system in the perifornical lateral hypothalamus has been recognized as a critical node in a complex network of neuronal systems controlling both physiology and behavior in vertebrates. Our understanding of the Hcrt/Orx system and its array of functions and actions has grown exponentially in merely 2 decades. This review will examine the latest progress in discerning the roles played by the Hcrt/Orx system in regulating homeostatic functions and in executing instinctive and learned behaviors. Furthermore, the gaps that currently exist in our knowledge of sex-related differences in this field of study are discussed. LA - English DB - MTMT ER -