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 - 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 - Gómez-Valadés, Alicia G. AU - Pozo, Macarena AU - Varela, Luis AU - Boudjadja, Mehdi Boutagouga AU - Ramírez, Sara AU - Chivite, Iñigo AU - Eyre, Elena AU - Haddad-Tóvolli, Roberta AU - Obri, Arnaud AU - Milà-Guasch, Maria AU - Altirriba, Jordi AU - Schneeberger, Marc AU - Imbernón, Mónica AU - Garcia-Rendueles, Angela R. AU - Gama-Perez, Pau AU - Rojo-Ruiz, Jonathan AU - Rácz, Bence AU - Alonso, Maria Teresa AU - Gomis, Ramon AU - Zorzano, Antonio AU - D’Agostino, Giuseppe AU - Alvarez, Clara V. AU - Nogueiras, Rubén AU - Garcia-Roves, Pablo M. AU - Horváth, Tamás AU - Claret, Marc TI - Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca2+ homeostasis with adipose tissue lipolysis JF - CELL METABOLISM J2 - CELL METAB VL - 33 PY - 2021 IS - 9 SP - 1820 EP - 1835 PG - 16 SN - 1550-4131 DO - 10.1016/j.cmet.2021.07.008 UR - https://m2.mtmt.hu/api/publication/32185509 ID - 32185509 LA - English DB - MTMT ER - TY - JOUR AU - Timper, Katharina AU - del Rio-Martin, Almudena AU - Cremer, Anna Lena AU - Bremser, Stephan AU - Alber, Jens AU - Giavalisco, Patrick AU - Varela, Luis AU - Heilinger, Christian AU - Nolte, Hendrik AU - Trifunovic, Aleksandra AU - Horváth, Tamás AU - Kloppenburg, Peter AU - Backes, Heiko AU - Bruening, Jens C. TI - GLP-1 Receptor Signaling in Astrocytes Regulates Fatty Acid Oxidation, Mitochondrial Integrity, and Function JF - CELL METABOLISM J2 - CELL METAB VL - 31 PY - 2020 IS - 6 SP - 1189 EP - 1205 PG - 17 SN - 1550-4131 DO - 10.1016/j.cmet.2020.05.001 UR - https://m2.mtmt.hu/api/publication/31519149 ID - 31519149 AB - Astrocytes represent central regulators of brain glucose metabolism and neuronal function. They have recently been shown to adapt their function in response to alterations in nutritional state through responding to the energy state-sensing hormones leptin and insulin. Here, we demonstrate that glucagon-like peptide (GLP)-1 inhibits glucose uptake and promotes beta-oxidation in cultured astrocytes. Conversely, postnatal GLP-1 receptor (GLP-1R) deletion in glial fibrillary acidic protein (GFAP)-expressing astrocytes impairs astrocyte mitochondrial integrity and activates an integrated stress response with enhanced fibroblast growth factor (FGF)21 production and increased brain glucose uptake. Accordingly, central neutralization of FGF21 or astrocyte-specific FGF21 inactivation abrogates the improvements in glucose tolerance and learning in mice lacking GLP-1R expression in astrocytes. Collectively, these experiments reveal a role for astrocyte GLP-1R signaling in maintaining mitochondrial integrity, and lack of GLP-1R signaling mounts an adaptive stress response resulting in an improvement of systemic glucose homeostasis and memory formation. LA - English DB - MTMT ER - TY - JOUR AU - Dore, Riccardo AU - Krotenko, Regina AU - Reising, Jan Philipp AU - Murru, Luca AU - Sundaram, Sivaraj Mohana AU - Di, Spiezio Alessandro AU - Mueller-Fielitz, Helge AU - Schwaninger, Markus AU - Joehren, Olaf AU - Mittag, Jens AU - Passafaro, Maria AU - Shanabrough, Marya AU - Horváth, Tamás AU - Schulz, Carla AU - Lehnert, Hendrik TI - Nesfatin-1 decreases the motivational and rewarding value of food JF - NEUROPSYCHOPHARMACOLOGY J2 - NEUROPSYCHOPHARMACOL VL - 45 PY - 2020 SP - 1645 EP - 1655 PG - 11 SN - 0893-133X DO - 10.1038/s41386-020-0682-3 UR - https://m2.mtmt.hu/api/publication/31319253 ID - 31319253 N1 - Funding Agency and Grant Number: Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [TR-SFB 134]; Deutsches Zentrum fur Diabetesforschung [01GI0925] Funding text: We thank Christine Eichholz and Angela Oldorp for excellent technical assistance, and the Department of Anatomy for the access to the laser capture microscope. This work was supported by grants from the Deutsche Forschungsgemeinschaft (TR-SFB 134 to CS and HL) and Deutsches Zentrum fur Diabetesforschung (DZD e.V. 01GI0925 to HL). AB - Homeostatic and hedonic pathways distinctly interact to control food intake. Dysregulations of circuitries controlling hedonic feeding may disrupt homeostatic mechanisms and lead to eating disorders. The anorexigenic peptides nucleobindin-2 (NUCB2)/nesfatin-1 may be involved in the interaction of these pathways. The endogenous levels of this peptide are regulated by the feeding state, with reduced levels following fasting and normalized by refeeding. The fasting state is associated with biochemical and behavioral adaptations ultimately leading to enhanced sensitization of reward circuitries towards food reward. Although NUCB2/nesfatin-1 is expressed in reward-related brain areas, its role in regulating motivation and preference for nutrients has not yet been investigated. We here report that both dopamine and GABA neurons express NUCB2/nesfatin-1 in the VTA. Ex vivo electrophysiological recordings show that nesfatin-1 hyperpolarizes dopamine, but not GABA, neurons of the VTA by inducing an outward potassium current. In vivo, central administration of nesfatin-1 reduces motivation for food reward in a high-effort condition, sucrose intake and preference. We next adopted a 2-bottle choice procedure, whereby the reward value of sucrose was compared with that of a reference stimulus (sucralose + optogenetic stimulation of VTA dopamine neurons) and found that nesfatin-1 fully abolishes the fasting-induced increase in the reward value of sucrose. These findings indicate that nesfatin-1 reduces energy intake by negatively modulating dopaminergic neuron activity and, in turn, hedonic aspects of food intake. Since nesfatin-1 ' s actions are preserved in conditions of leptin resistance, the present findings render the NUCB2/nesfatin-1 system an appealing target for the development of novel therapeutical treatments towards obesity. LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Dávid Sándor AU - Tóth, István AU - Jócsák, Gergely AU - Bartha, Tibor AU - Frenyó V., László AU - Bárány, Zoltán Balázs AU - Horváth, Tamás AU - Zsarnovszky, Attila TI - Metabolic Lateralization in the Hypothalamus of Male Rats Related to Reproductive and Satiety States JF - REPRODUCTIVE SCIENCES J2 - REPROD SCI VL - 27 PY - 2020 IS - 5 SP - 1197 EP - 1205 PG - 9 SN - 1933-7191 DO - 10.1007/s43032-019-00131-3 UR - https://m2.mtmt.hu/api/publication/31260011 ID - 31260011 LA - English DB - MTMT ER - TY - JOUR AU - Taylor-Giorlando, Melissa AU - Scheinost, Dustin AU - Ment, Laura AU - Rothman, Dough AU - Horváth, Tamás TI - Prefrontal Cortical and Behavioral Adaptations to Surgical Delivery Mediated by Metabolic Principles JF - CEREBRAL CORTEX J2 - CEREB CORTEX VL - 29 PY - 2019 IS - 12 SP - 5061 EP - 5071 PG - 11 SN - 1047-3211 DO - 10.1093/cercor/bhz046 UR - https://m2.mtmt.hu/api/publication/31205043 ID - 31205043 N1 - Funding Agency and Grant Number: NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [AG052005, AG052986, AG051459, DK111178, NKFI-126998]; Hungarian National Research, Development and Innovation Office Funding text: This study was supported by NIH grants AG052005, AG052986, AG051459, DK111178 and NKFI-126998 from the Hungarian National Research, Development and Innovation Office (T.L.H). AB - We previously observed an association between mode of delivery and brain mitochondrial mechanisms in pups. We also showed that mitochondrial processes impact adult behavior. However, no experimental data is available to causally connect mode of delivery with cellular processes of neurons in the cerebral cortex and adult behavior. Here we show that surgical delivery of pups alters mitochondrial dynamics and spine synapses of layer 3 pyramidal neurons of the prefrontal cortex compared to the values of mice delivered vaginally. These alterations in ultrastructure seen in adult mice delivered surgically were associated with the development of behavioral phenotypes resembling those characteristic of animal models of psychiatric illness. This included impaired performance in prepulse inhibition as well as hyperlocomotion in the open field and elevated plus maze tests. Knocking out a mitochondria-related gene, UCP-2, blocked cellular and behavioral adaptations induced by surgical delivery. These results highlight a crucial role for brain mitochondrial adaptations in the process of birth to affect neuronal circuitry in support of normal and altered adult behaviors. Further, these findings were supported with neuroimaging data from human neonates delivered vaginally and surgically, suggesting that the murine findings have human clinical relevance. LA - English DB - MTMT ER - TY - JOUR AU - Stutz, Bernardo AU - Nasrallah, Carole AU - Nigro, Mariana AU - Curry, Daniel AU - Liu, Zhong-Wu AU - Gao, Xiao-Bing AU - Elsworth, John D. AU - Mintz, Liat AU - Horváth, Tamás TI - Dopamine neuronal protection in the mouse Substantia nigra by GHSR is independent of electric activity JF - MOLECULAR METABOLISM J2 - MOL METAB VL - 24 PY - 2019 SP - 120 EP - 138 PG - 19 SN - 2212-8778 DO - 10.1016/j.molmet.2019.02.005 UR - https://m2.mtmt.hu/api/publication/30707414 ID - 30707414 N1 - Funding Agency and Grant Number: NIH from the Hungarian National Research, Development and Innovation Office [AG052005, AG052986, AG051459, DK111178, NKFI-126998]; Michael J. Fox Foundation; Science without Borders fellowship from The Brazilian Federal Agency for Support and Assessment of Post-graduate Education (CAPES); Science without Borders fellowship from the National Council for Scientific and Technological Development (CNPq) Funding text: This study was supported by NIH grants AG052005, AG052986, AG051459, DK111178 and NKFI-126998 from the Hungarian National Research, Development and Innovation Office (T.L.H), and the Michael J. Fox Foundation.; B.S. and M.N. are recipients of the Science without Borders fellowships from The Brazilian Federal Agency for Support and Assessment of Post-graduate Education (CAPES) and from the National Council for Scientific and Technological Development (CNPq), respectively. AB - Objective: Dopamine neurons in the Substantia nigra (SN) play crucial roles in control of voluntary movement. Extensive degeneration of this neuronal population is the cause of Parkinson's disease (PD). Many factors have been linked to SN DA neuronal survival, including neuronal pacemaker activity (responsible for maintaining basal firing and DA tone) and mitochondrial function. DIn-101, a naturally occurring splice variant of the human ghrelin gene, targets the ghrelin receptor (GHSR) present in the SN DA cells. Ghrelin activation of GHSR has been shown to protect SN DA neurons against 1-methyl-4-phenyl-1,2,5,6 tetrahydropyridine (MPTP) treatment. We decided to compare the actions of DIn-101 with ghrelin and identify the mechanisms associated with neuronal survival. Methods: Histologial, biochemical, and behavioral parameters were used to evaluate neuroprotection. Inflammation and redox balance of SN DA cells were evaluated using histologial and real-time PCR analysis. Designer Receptors Exclusively Activated by Designer Drugs (DREADD) technology was used to modulate SN DA neuron electrical activity and associated survival. Mitochondria! dynamics in SN DA cells was evaluated using electron microscopy data. Results: Here, we report that the human isoform displays an equivalent neuroprotective factor. However, while exogenous administration of mouse ghrelin electrically activates SN DA neurons increasing dopamine output, as well as locomotion, the human isoform significantly suppressed dopamine output, with an associated decrease in animal motor behavior. Investigating the mechanisms by which GHSR mediates neuroprotection, we found that dopamine cell-selective control of electrical activity is neither sufficient nor necessary to promote SN DA neuron survival, including that associated with GHSR activation. We found that DIn101 pre-treatment diminished MPTP-induced mitochondria! aberrations in SN DA neurons and that the effect of DIn101 to protect dopamine cells was dependent on mitofusin 2, a protein involved in the process of mitochondria! fusion and tethering of the mitochondria to the endoplasmic reticulum. Conclusions: Taken together, these observations unmasked a complex role of GHSR in dopamine neuronal protection independent on electric activity of these cells and revealed a crucial role for mitochondrial dynamics in some aspects of this process. (C) 2019 Published by Elsevier GmbH. LA - English DB - MTMT ER -