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AG Lutz



Leitung:
Prof. Dr. Beat Lutz

Scientific Managing Director LIR, Professor and Director of Institute of Physiological Chemistry University Medical Center of the Johannes Gutenberg-University Mainz

Mitarbeitende

Annika Beer, Doktorandin

Larglinda Islami, Doktorandin

Florian König, TA

Verena Könning, TA

Dr. Inigo Ruiz de Azua, Wissenschaftler

Dr. Margaryta Tevosian, Postdoktorandin

Dr. Constance Vennin, Postdoktorandin

Dr. Jingzhang Wei, Postdoktorand

Kurzbeschreibung der Arbeitsgruppe

Die Arbeitsgruppe untersucht die Bedeutung des Endocannabinoid-Systems als Mediator von Stressresilienz. Hierzu wird dieses neuromodulatorische System mittels genetischer, epigenetischer und pharmakologischer Methoden in Mäusen untersucht. Es werden nicht nur Gehirnfunktionen bezüglich Stressresilienz untersucht, sondern auch periphere neuronale, hormonelle und immunologische Mechanismen. Physische Aktivität kann ebenfalls die Stressantwort und die Resilienz beeinflussen. Es werden auch Untersuchungen über Lernen und Gedächtnis und Furchtextinktion eingeschlossen, da diese Prozesse ebenfalls die Stressresilienz betreffen.

Aktuelle Forschungsprojekte
  • Transkriptionale Netzwerkanalysen in Stressresilienz mittels Einzelzell-Sequenzierungen in ausgewählten neuralen Zellpopulationen in der Maus
  • Beschreibung von neuronalen Aktivitäten während der Furchtextinktion
  • Signalmediatoren im Blut zur Vermittlung von trainingsinduzierter Stressresilienz
  • Endocannabinoide in der Vermittlung der Stressresilienz
  • Kartierung aktivierter Gehirnregionen in Stressresilienz
  • Analyse von Gehirn-Organoiden, entwickelt aus induzierten humanen pluripotenten Stammzellen (iPSCs) und die Beeinflussung durch das Endocannabinoid-System
Externe Kooperationspartner:innen
  • Prof. Dr. Rafael Maldonado, Department of Experimental and Health Sciences, University Pompeu Fabra, Barcelona, Spanien
  • Prof. Dr. Stefan Remy, LIN Magdeburg
  • Dr. Giovanni Marsicano, INSERM Bordeaux, Frankreich
  • Prof. Dr. Dr. Michael Schmeißer, UM Mainz
Förderungen
  • DFG
  • ERA-NET Neuron / BMBF
  • Leibniz Gemeinschaft
Key Publications

Busquets-Garcia A, Gomis-González M, Srivastava RK, Cutando L, Ortega-Alvaro A, Ruehle S, Remmers F, Bindila L, Bellocchio L, Marsicano G, Lutz B*, Maldonado R*, Ozaita A* (2016). Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation. Proc Natl Acad Sci USA 113:9904-9. *shared senior authors

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Busch AM, Kovlyagina I, Lutz B, Todorov H, Gerber S (2022) beeRapp: an R shiny app for automated high-throughput explorative analysis of multivariate behavioral data. Bioinform Adv 2(1):vbac082. doi: 10.1093/bioadv/vbac082.

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Domingo-Rodriguez L, Ruiz de Azua I, Dominguez E, Senabre E, Serra I, Kummer S, Navandar M, Baddenhausen S, Hofmann C, Andero R, Gerber S, Navarrete M, Dierssen M, Lutz B*, Martín-García E*, Maldonado R* (2020). A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction. Nat Commun 11:782. doi: 10.1038/s41467-020-14458-y (* equal contributions)

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Fuss J, Steinle J, Bindila L, Auer MK, Kirchherr H, Lutz B, Gass P (2015). A runner's high depends on cannabinoid receptors in mice. Proc Natl Acad Sci USA 112:13105-13108

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Jimenez-Blasco D, Busquets-Garcia A, Hebert-Chatelain E, Serrat R, Vicente-Gutierrez C, Ioannidou C, Gómez-Sotres P, Lopez-Fabuel I, Resch-Beusher M, Resel E, Arnouil D, Saraswat D, Varilh M, Cannich A, Julio-Kalajzic F, Bonilla-Del Río I, Almeida A, Puente N, Achicallende S, Lopez-Rodriguez ML, Jollé C, Déglon N, Pellerin L, Josephine C, Bonvento G, Panatier A, Lutz B, Piazza PV, Guzmán M, Bellocchio L, Bouzier-Sore AK, Grandes P, Bolaños JP, Marsicano G (2020) Glucose metabolism links astroglial mitochondria to cannabinoid effects. Nature. 583:603-608. doi: 10.1038/s41586-020-2470-y

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Kalisch R, Baker DG, Basten U, Boks MP, Bonanno GA, Brummelman E, Chmitorz A, Fernàndez G, Fiebach CJ, Galatzer-Levy I, Geuze E, Groppa S, Helmreich I, Hendler T, Hermans EJ, Jovanovic T, Kubiak T, Lieb K, Lutz B, Müller MB, Murray RJ, Nievergelt CM, Reif A, Roelofs K, Rutten BPF, Sander D, Schick A, Tüscher O, Diest IV, Harmelen AV, Veer IM, Vermetten E, Vinkers CH, Wager TD, Walter H, Wessa M, Wibral M, Kleim B (2017). The resilience framework as a strategy to combat stress-related disorders. Nat Hum Behav (11):784-790. doi: 10.1038/s41562-017-0200-8.z

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Lange MD, Daldrup T, Remmers R, Szkudlarek HJ, Lesting J, Guggenhuber G, Ruehle S, Jüngling K, Seidenbecher T, Lutz B, Pape HC (2017). Cannabinoid CB1 receptors in distinct circuits of the extended amygdala determine fear responsiveness to unpredictable threat. Mol Psychiatry 22(10):1422-1430.

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Leschik J, Gentile A, Cicek C, Péron S, Tevosian M, Beer A, Radyushkin K, Bludau A, Ebner K, Neumann I, Singewald N, Berninger B, Lessmann V, Lutz B (2022) Brain-derived neurotrophic factor expression in serotonergic neurons improves stress resilience and promotes adult hippocampal neurogenesis. Prog Neurobiol 217:102333. doi: 10.1016/j.pneurobio.2022.102333.

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Leschik J, Lutz B, Gentile A (2021). Stress-Related Dysfunction of Adult Hippocampal Neurogenesis-An Attempt for Understanding Resilience? Int J Mol Sci 22(14):7339.

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Lomazzo E, Bindila L, Remmers F, Lerner R, Schwitter C, Hoheisel U, Lutz B (2015). Therapeutic potential of inhibitors of endocannabinoid degradation for the treatment of stress-related hyperalgesia in an animal model of chronic pain. Neuropsychopharmacol 40:488-501.

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Lutz B, Marsicano G, Maldonado R, Hillard CJ (2015). The endocannabinoid system in gating fear, anxiety and stress. Nat Rev Neurowsci 16:705-718.

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Martínez-Torres S, Bergadà-Martínez A, Ortega JE, Galera-López L, Hervera A, de Los Reyes-Ramírez L, Ortega-Álvaro A, Remmers F, Muñoz-Moreno E, Soria G, Del Río JA, Lutz B, Ruíz-Ortega JÁ, Meana JJ, Maldonado R, Ozaita A (2023). Peripheral CB1 receptor blockade acts as a memory enhancer through a noradrenergic mechanism. Neuropsychopharmacology 48(2):341-350.

Navandar M, Elena Martín-García E, Maldonado R, Lutz B, Gerber S, Ruiz de Azua I# (2021). Transcriptomic signatures in prefrontal cortex confer vulnerability versus resilience to food and cocaine addiction-like behavior in mouse. Scientific Reports 11(1):9076. (#equal contributions)

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Pascual Cuadrado D, Todorov H, Lerner R, Islami L, Bindila L, Gerber S, Lutz B (2022) Long-term molecular differences between resilient and susceptible mice after a single traumatic exposure. Br J Pharmacol 179(17):4161-4180. doi: 10.1111/bph.15697.

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Ruiz de Azua I, Lutz B (2019). Multiple endocannabinoid-mediated mechanisms in the regulation of energy homeostasis in brain and peripheral tissues. Cell Mol Life Sci 76(7):1341-1363. doi: 10.1007/s00018-018-2994-6.

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Ruiz de Azua I, Mancini G, Srivastava RK, Rey AA, Cardinal P, Tedesco L, Zingaretti CM, Sassmann A, Quarta C, Schwitter C, Conrad A, Wettschureck N, Vemuri VK, Makriyannis A, Hartwig J, Mendez-Lago M, Bindila L, Monory K, Giordano A, Cinti S, Marsicano G, Offermanns S, Nisoli E, Pagotto U, Cota D, Lutz B (2017). Adipocyte cannabinoid receptor CB1 regulates energy homeostasis and alternatively activated macrophages. J Clin Invest 127:4148-4162. doi: 10.1172/JCI83626

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Ruiz de Azua I*, Martin-Garcia E*, Domingo-Rodriguez L, Aparisi Rey A, Pascual Cuadrado D, Islami L, Turunen P, Remmers F, Lutz B#, Maldonado R# (2021). Cannabinoid CB1 receptor in dorsal telencephalic glutamatergic neurons drives overconsumption of palatable food and obesity. Neuropsychopharmacol 46(5):982-991. (*equal contribution, # shared senior authorship)

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Suárez J, Rivera P, Aparisi Rey A, Pérez-Martín M, Arrabal S, Rodríguez de Fonseca F, Ruiz de Azua I, Lutz B (2019). Adipocyte cannabinoid CB1 receptor deficiency alleviates high fat diet-induced memory deficit, depressive-like behavior, neuroinflammation and impairment in adult neurogenesis. Psychoneuroendocrinology 110:104418. doi: 10.1016/j.psyneuen.2019.104418

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Srivastava RK, Lutz B, Ruiz de Azua I (2022) The Microbiome and Gut Endocannabinoid System in the Regulation of Stress Responses and Metabolism. Front Cell Neurosci 16:867267. doi: 10.3389/fncel.2022.867267.

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Vennin C, Hewel C, Todorov H, Wendelmuth M, Radyushkin K, Heimbach A, Horenko I, Ayash S, Müller MB, Schweiger S, Gerber S, Lutz B (2022) A Resilience Related Glial-Neurovascular Network Is Transcriptionally Activated after Chronic Social Defeat in Male Mice. Cells 11(21):3405. doi: 10.3390/cells11213405

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Zimmermann T, Maroso M, Beer A, Baddenhausen S, Ludewig S, Fan W, Vennin C, Loch S, Berninger B, Hofmann C, Korte M, Soltesz I, Lutz B, Leschik J (2018). Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus. Cereb Cortex 28(12):4454-4471. doi: 10.1093/cercor/bhy258.

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Zimmermann T, Bartsch JC, Beer A, Lomazzo E, Guggenhuber S, Lange MD, Bindila L, Pape HC, Lutz B (2019). Impaired anandamide/palmitoylethanolamide signaling in hippocampal glutamatergic neurons alters synaptic plasticity, learning, and emotional responses. Neuropsychopharmacology 44(8):1377-1388. doi: 10.1038/s41386-018-0274-7

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Ruiz de Azua I*, Martin-Garcia E*, Domingo-Rodriguez L, Aparisi Rey A, Pascual Cuadrado D, Islami L, Turunen P, Remmers F, Lutz B#, Maldonado R# (2021). Cannabinoid CB1 receptor in dorsal telencephalic glutamatergic neurons drives overconsumption of palatable food and obesity. Neuropsychopharmacol 46(5):982-991. (*equal contribution, # shared senior authorship)

>> Link zu Pubmed