Project

Back to overview

Elucidating the Role of Lipid Metabolism for Life-long Neurogenesis in the Mammalian Brain

English title Elucidating the Role of Lipid Metabolism for Life-long Neurogenesis in the Mammalian Brain
Applicant Jessberger Sebastian
Number 157859
Funding scheme SNSF Consolidator Grants
Research institution
Institution of higher education University of Zurich - ZH
Main discipline Neurophysiology and Brain Research
Start/End 01.07.2015 - 30.06.2020
Approved amount 1'746'842.00
Show all

All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Cellular Biology, Cytology

Keywords (6)

hippocampus; stem cell; depression; neurogenesis; disease modeling; metabolism

Lay Summary (German)

Lead
Neurale Stammzellen produzieren lebenslang neue Nervenzellen in bestimmten Hirnregionen (adulte Neurogenese). Dieser Prozess ist wichtig für bestimmte Lern- und Gedächtnisprozessen und eine reduzierte bzw. veränderte Neurogenese ist assoziiert mit einer Reihe von neuropsychiatrischen Erkrankungen (z.B. mit Depressionen und Epilepsie). Die Aktivität von neuralen Stammzellen wird durch einen spezialisierten zellulären Metabolismus reguliert. Im Rahmen des vorliegenden Projektes soll untersucht werden, welche metabolischen Veränderungen von der Stammzelle zur neugeborenen Nervenzelle stattfinden und ob allenfalls Signalwege therapeutisch nutzbar gemacht werden können - etwa um im Tiermodell bei Depressionen die Neurogenese zu erhöhen. Ausserdem ist es Ziel herausfinden, inwiefern ein veränderter, stammzell-assozierter Zellmetabolismus bei kognitiven Prozessen im menschlichen Gehirn eine Rolle spielt.
Lay summary

 

Neurale Stammzellen im Gehirn produzieren lebenslang neue Nervenzellen. Dieser Prozess, adulte Neurogenese genannt, ist wichtig für verschiedene Formen von Lernen und Gedächtnis. Zudem steht eine verringerte oder veränderte Neurogenese im Zusammenhang mit einer Vielzahl von neuropsychiatrischen Erkrankungen wie Depressionen und Epilepsie. Die molekularen Mechanismen, die der adulten Neurogenese zugrundeliegen, sind zum grössten Teil noch unbekannt. In früheren Arbeiten haben wir einen neuen Mechanismus entdeckt, der die Aktivität von neuralen Stammzellen über eine Regulation des zellulären Metabolismus steuert. Im Rahmen des vorliegenden Projektes soll untersucht werden, welche metabolischen Veränderungen von der Stammzelle zur neugeborenen Nervenzelle stattfinden und ob allenfalls Signalwege therapeutisch nutzbar gemacht werden können – etwa um im Tiermodell bei Depressionen die Neurogenese zu erhöhen. Ausserdem ist es Ziel herausfinden, inwiefern ein veränderter, stammzell-assozierter Zellmetabolismus bei kognitiven Prozessen im menschlichen Gehirn eine Rolle spielt.

Direct link to Lay Summary Last update: 24.02.2015

Responsible applicant and co-applicants

Employees

Publications

Publication
FASN-Dependent Lipid Metabolism Links Neurogenic Stem/Progenitor Cell Activity to Learning and Memory Deficits.
(2020), FASN-Dependent Lipid Metabolism Links Neurogenic Stem/Progenitor Cell Activity to Learning and Memory Deficits., in Cell Stem Cell, 1-24.
Lateral dispersion is required for circuit integration of newly generated dentate granule cells
Wang J., Shen J., Kirschen G.W., Gu Y., Jessberger S., Ge S. (2019), Lateral dispersion is required for circuit integration of newly generated dentate granule cells, in Nature Communications, 10(1), 1-9.
Mechanisms of cellular rejuvenation
Denoth-Lippuner A., Jessberger S. (2019), Mechanisms of cellular rejuvenation, in FEBS Letters, 593(23), 3381-3392.
Palmitoylation of BMPR1a regulates neural stem cell fate
Wegleiter T., Buthey K., Gonzalez-Bohorquez D., Hruzova M., Imtiaz M.K.B., Abegg A., Mebert I., Molteni A., Kollegger D., Pelczar P., Jessberger S. (2019), Palmitoylation of BMPR1a regulates neural stem cell fate, in Proceedings of the National Academy of Sciences of the United States of America, 116(51), 25688-25696.
Sleep or deplete: how the choroid plexus helps to keep neural stem cells in balance
Wegleiter T., Jessberger S. (2019), Sleep or deplete: how the choroid plexus helps to keep neural stem cells in balance, in EMBO Journal, 38(17), 1-3.
A novel environment-evoked transcriptional signature predicts reactivity in single dentate granule neurons
Jaeger B.N., Linker S.B., Parylak S.L., Barron J.J., Gallina I.S., Saavedra C.D., Fitzpatrick C., Lim C.K., Schafer S.T., Lacar B., Jessberger S., Gage F.H. (2018), A novel environment-evoked transcriptional signature predicts reactivity in single dentate granule neurons, in Nature Communications, 9(1), 1-15.
De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination
Montani L., Pereira J.A., Norrmén C., Pohl H.B.F., Tinelli E., Trötzmüller M., Figlia G., Dimas P., von Niederhäusern B., Schwager R., Jessberger S., Semenkovich C.F., Köfeler H.C., Suter U. (2018), De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination, in Journal of Cell Biology, 217(4), 1353-1368.
Human Adult Neurogenesis: Evidence and Remaining Questions
Kempermann G., Gage F.H., Aigner L., Song H., Curtis M.A., Thuret S., Kuhn H.G., Jessberger S., Frankland P.W., Cameron H.A., Gould E., Hen R., Abrous D.N., Toni N., Schinder A.F., Zhao X., Lucassen P.J., Frisén J. (2018), Human Adult Neurogenesis: Evidence and Remaining Questions, in Cell Stem Cell, 23(1), 25-30.
Life Science Alliance, from the Academic Editors
Cooper J.P., Ginhoux F., Jessberger S., Overholtzer M. (2018), Life Science Alliance, from the Academic Editors, in Life science alliance, 1(1), 201800044-201800044.
Live imaging of neurogenesis in the adult mouse hippocampus
Pilz G.-A., Bottes S., Betizeau M., Jörg D.J., Carta S., Simons B.D., Helmchen F., Jessberger S. (2018), Live imaging of neurogenesis in the adult mouse hippocampus, in Science, 359(6376), 658-662.
Quiescent Endothelial Cells Upregulate Fatty Acid β-Oxidation for Vasculoprotection via Redox Homeostasis
Kalucka J., Bierhansl L., Conchinha N.V., Missiaen R., Elia I., Brüning U., Scheinok S., Treps L., Cantelmo A.R., Dubois C., de Zeeuw P., Goveia J., Zecchin A., Taverna F., Morales-Rodriguez F., Brajic A., Conradi L.-C., Schoors S., Harjes U., Vriens K., Pilz G.-A., Chen R., Cubbon R., Thienpont B., Cruys B., Wong B.W., Ghesquière B., Dewerchin M., De Bock K., Sagaert X., Jessberger S., Jones E.A.V., Gallez B., Lambrechts D., Mazzone M., Eelen G., Li X., Fendt S.-M., Carmeliet P. (2018), Quiescent Endothelial Cells Upregulate Fatty Acid β-Oxidation for Vasculoprotection via Redox Homeostasis, in Cell Metabolism, 28(6), 880-e13.
A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity.
Knobloch Marlen, Pilz Gregor-Alexander, Ghesquière Bart, Kovacs Werner J, Wegleiter Thomas, Moore Darcie L, Hruzova Martina, Zamboni Nicola, Carmeliet Peter, Jessberger Sebastian (2017), A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity., in Cell reports, (9), 2144-2155.
The role of fatty acid beta-oxidation in lymphangiogenesis
Wong Brian W., Wang Xingwu, Zecchin Annalisa, Thienpont Bernard, Cornelissen Ivo, Kalucka Joanna, Garcia-Caballero Melissa, Missiaen Rindert, Huang Hongling, Burning Ulrike, Blacher Silvia, Vinckier Stefan, Goveia Jermaine, Knobloch Marlen, Zhao Hui, Dierkes Cathrin, Shi Chenyan, Haegerling Rene, Moral-Darde Veronica, Wyns Sabine, Lippens Martin, Jessberger Sebastian, Fendt Sarah-Maria, Luttun Aernout, Noel Agnes, Kiefer Friedemann, Ghesquiere Bart, Moons Lieve, Schoonjans Luc, Dewerchin Mieke, Eelen Guy, Lambrechts Diether, Carmeliet Peter (2017), The role of fatty acid beta-oxidation in lymphangiogenesis, in NATURE, (7639), 49-49.
Creating Age Asymmetry: Consequences of Inheriting Damaged Goods in Mammalian Cells
Moore Darcie, Jessberger Sebastian (2017), Creating Age Asymmetry: Consequences of Inheriting Damaged Goods in Mammalian Cells, in CellPress, 82.
Metabolism and neurogenesis
Knobloch Marlen, Jessberger Sebastian (2017), Metabolism and neurogenesis, in Elsevier, 45.
Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis
Beckervordersandforth R., Ebert B., Schäffner I., Moss J., Fiebig C., Shin J., Moore D.L., Ghosh L., Trinchero M.F., Stockburger C., Friedland K., Steib K., von Wittgenstein J., Keiner S., Redecker C., Hölter S.M., Xiang W., Wurst W., Jagasia R., Schinder A.F., Ming G.-L., Toni N., Jessberger S., Song H., Lie D.C. (2017), Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis, in Neuron, 93(3), 560-573.
Unexpected help to repair the cerebellum
Jaeger B.N., Jessberger S. (2017), Unexpected help to repair the cerebellum, in Nature Neuroscience, 20(10), 1319-1321.

Datasets

FASN-dependent metabolism links neurogenic stem/progenitor cell activity to intellectual disability

Author Jaeger, Baptiste
Publication date 18.03.2020
Persistent Identifier (PID) GSE115851
Repository GEO


Palmitoylation of BMPR1a regulates neural stem cell fate

Author Wegleiter, Thomas
Publication date 27.11.2019
Persistent Identifier (PID) PXD014355
Repository PRIDE


A fatty acid oxidation-dependent metabolic shift regulates adult neural stem cell quiescence

Author Wegleiter, Thomas
Publication date 15.11.2019
Persistent Identifier (PID) PXD005598
Repository PRIDE


Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Seminar Series, Faculty of Medical Sciences, Kyushu University Talk given at a conference Heterogeneity of neurogenic stem cells in the adult brain 04.12.2019 Fukuoka, Japan Jessberger Sebastian;
42nd Meeting Molecular Biology Society Japan Talk given at a conference Molecular and Cellular Mechanisms Regulating Neural Stem Cell Activity 03.12.2019 Fukuoka, Japan Jessberger Sebastian;
Crick Institute Seminar Series Talk given at a conference Functional and molecular diversity of neural stem cells in the adult brain 25.09.2019 London, Great Britain and Northern Ireland Jessberger Sebastian;
INFORM meeting Talk given at a conference Metabolic control of neural stem cells 01.09.2019 Amsterdam, Netherlands Jessberger Sebastian;
ISSCR Annual meeting Talk given at a conference Stem cell divisions in the adult brain 26.06.2019 Los Angeles , United States of America Jessberger Sebastian;
Marabou Foundation conference Talk given at a conference Neural stem cells and aging 14.06.2019 Stockholm, Sweden Jessberger Sebastian;
4th Eurogenesis meeting Talk given at a conference Heterogeneity of neurogenic stem cells in the adult brain 10.06.2019 Bordeaux, France Jessberger Sebastian;
XVI Portuguese Society for Neuroscience (Keynote lecture) Talk given at a conference Elucidating the molecular and cellular dynamics of neurogenesis 29.05.2019 Lisbon, Portugal Jessberger Sebastian;
DZNE Dresden Opening Symposium (Keynote lecture) Talk given at a conference Single cell dynamics of adult neural stem cells 09.05.2019 Dresden, Germany Jessberger Sebastian;
EMBO YIP Morphogenesis meeting Talk given at a conference Brain stem cells 06.05.2019 Copenhagen, Denmark Jessberger Sebastian;
CERVO Brain Research Center at Université Laval Seminar Series Talk given at a conference Elucidating the molecular and cellular dynamics of neurogenesis 25.04.2019 Quebec City, Canada Jessberger Sebastian;
2nd Neurogenesis Fusion conference Talk given at a conference Heterogeneity of neurogenic stem cells in the adult brain 05.03.2019 Nassau, Bahamas Jessberger Sebastian;
EMBO Conference Molecular Neuroscience: From cells to circuits in health and disease Talk given at a conference Principles of neurogenic cell divisions in the adult brain 04.02.2019 Bangalore, India Jessberger Sebastian;
IREM Seminar Series Talk given at a conference Elucidating the molecular and cellular mechanisms of neural stem cell activity 28.01.2019 Zurich, Switzerland Jessberger Sebastian;
IGBMC Seminar Series Talk given at a conference Molecular and cellular mechanisms regulating neural stem cell activity 25.01.2019 Zurich, Switzerland Jessberger Sebastian;
3rd BioMed PhD day (Keynote) Talk given at a conference How neural stem cells generate new neurons throughout life 18.01.2019 Barcelona, Spain Jessberger Sebastian;
1st CSCB-EMBO Young Investigator Conference Talk given at a conference Molecular mechanisms regulating neural stem cell activity 22.11.2018 Suzhou, China Jessberger Sebastian;
Alexander von Humboldt Stiftung / Auswahlausschuss Talk given at a conference Abendvortrag: Neue Nervenzellen für alte Gehirne 15.11.2018 Bonn, Germany Jessberger Sebastian;
Seminar series, Instituto de Neurociencias de Alicante Talk given at a conference Molecular and cellular mechanisms regulating neural stem cell activity 09.11.2018 Alicante, Spain Jessberger Sebastian;
3rd Gage Lab Symposium Talk given at a conference Cellular principles of adult neurogenesis 30.10.2018 La Jolla, United States of America Jessberger Sebastian;
GRK 2162 Neurodevelopment and Vulnerability of the Central Nervous System Talk given at a conference Elucidating the molecular and cellular dynamics of neurogenesis in the adult hippocampus 19.09.2018 Erlangen, Germany Jessberger Sebastian;
Lund Stem Cell Center retreat (Keynote lecture) Talk given at a conference Molecular mechanisms regulating neural stem cell activity 06.09.2018 Bastad, Sweden Jessberger Sebastian;
Stem Cell Conference Basel Talk given at a conference Cellular principles of lifelong neurogenesis 29.08.2018 Basel, Switzerland Jessberger Sebastian;
Abcam Adult Neurogenesis 2018 Conference Talk given at a conference Molecular and Cellular Mechanisms controlling neural stem cell activity 02.05.2018 Dresden, Germany Jessberger Sebastian;
3rd EMBO YIP Morphogenesis Talk given at a conference Brain Stem Cells 11.04.2018 Marseille, France Jessberger Sebastian;
17th Day of Clinical Research  Talk given at a conference How the brain builds new nerve cells throughout life 05.04.2018 Zurich, Switzerland Jessberger Sebastian;
Alpine Anatomical Research Conference (Keynote Lecture) Talk given at a conference Molecular and Cellular Mechanisms controlling neural stem cell activity 25.03.2018 Obergurgl, Austria Jessberger Sebastian;
Brain & Heart Symposium 2018 (Keynote Lecture) Talk given at a conference Mechanisms of Neurogenesis 04.03.2018 Sils Maria, Switzerland Jessberger Sebastian;
Life Science Zurich / Translational Medicine Event Talk given at a conference Understanding the principles of somatic stem cell regulation 22.01.2018 Zurich, Switzerland Jessberger Sebastian;
Cambridge Stem Cell Institute Seminar series Talk given at a conference Molecular and cellular mechanisms regulating neural stem cell activity 11.09.2017 Cambridge, Great Britain and Northern Ireland Jessberger Sebastian;
Randall Seminar series / King’s College Talk given at a conference Mechanisms of Neurogenesis 09.05.2017 London, Great Britain and Northern Ireland Jessberger Sebastian;
EMBO Young Investigator meeting Talk given at a conference Mechanisms of Neurogenesis 03.03.2017 Paris, France Jessberger Sebastian;
MDC Lecture series Talk given at a conference Molecular and cellular mechanisms regulating neural stem cell activity 20.01.2017 Berlin, Germany Jessberger Sebastian;
BrainDisC Conference Bernstein Center Talk given at a conference Molecular and cellular mechanisms regulating neurogenesis 27.09.2016 Freiburg, Germany Jessberger Sebastian;
Bridges to the Future: German-Israeli Scientific Relations Talk given at a conference Molecular and cellular mechanisms regulating neurogenesis 21.09.2016 Tel Aviv, Israel Jessberger Sebastian;
12th European Congress on Epileptology Talk given at a conference Molecular and cellular mechanisms regulating neurogenesis 11.09.2016 Prague, Czech Republic Jessberger Sebastian;
3rd Neurogenesis Meeting Talk given at a conference Cell division in the adult brain 11.07.2016 Bordeaux, France Jessberger Sebastian;
5th Lugano Stem Cell Meeting Talk given at a conference Molecular and cellular control of neural stem cell activity 20.06.2016 Lugano, Switzerland Jessberger Sebastian;
6th International IZKF Symposium Talk given at a conference Stem cell aging and cell division 16.06.2016 Kloster Banz, Germany Jessberger Sebastian;
REMBO meeting (Can Tallada) Talk given at a conference Mechanisms of stem cell maintenance 08.06.2016 Girona, Spain Jessberger Sebastian;
Wyss Center Lecture Series Talk given at a conference Molecular and cellular mechanisms regulating neural stem cell activity 31.05.2016 Zürich, Switzerland Jessberger Sebastian;
What's New in Adult Neurogenesis?(College de France) Talk given at a conference A mechanism for asymmetric segregation of age in neural stem cells 19.05.2016 Paris, France Jessberger Sebastian;
Institut Pasteur Seminar series Talk given at a conference Molecular and cellular mechanisms regulating neural stem cell activity 22.04.2016 Paris, France Jessberger Sebastian;
ULB Interdisciplinary Seminars Talk given at a conference Mechanisms of Neurogenesis 14.04.2016 Brussels, Belgium Jessberger Sebastian;
EMBO sectorial meeting Tissue Morphogenesis Talk given at a conference Asymmetric cell division of neural stem cell 07.02.2016 Dresden, Germany Jessberger Sebastian;


Self-organised

Title Date Place
Fusion Conference: Neurogenesis: Implications for Lifelong Development and Disease 02.03.2016 Cancun, Mexico

Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions 100 Ways of Thinking / ZNZ brain Weekend German-speaking Switzerland 2018
Other activities Rämibühl 1. Klasse "Stadt des Wissens" German-speaking Switzerland 2017

Awards

Title Year
Robert Bing Prize of the Swiss Academy of Medical Sciences 2016

Associated projects

Number Title Start Funding scheme
196869 Intravital imaging-based analyses of stem cell-associated structural and functional plasticity of the murine hippocampus throughout life 01.11.2020 Project funding (Div. I-III)
156943 Mechanisms and functional relevance of mitochondrial metabolism for adult neural stem cell activity 01.01.2015 Project funding (Div. I-III)
138335 Molekular Mechanismen Adulter Neurogenese 01.10.2011 Project funding (Div. I-III)
196869 Intravital imaging-based analyses of stem cell-associated structural and functional plasticity of the murine hippocampus throughout life 01.11.2020 Project funding (Div. I-III)

Abstract

Neural stem/progenitor cells (NSPCs) generate new neurons throughout life in discrete areas of the mammalian brain. This process, called adult neurogenesis, is critical for tissue homeostasis and adult-brain function. Furthermore, altered or failing neurogenesis has been associated with a number of neuro-psychiatric diseases such as major depression and age-related cognitive decline. To ensure the life-long generation of newborn neurons, the activity of NSPCs is tightly controlled by a number of extrinsic and intrinsic mechanisms. We have previously identified a critical role for specialized lipid metabolism in NSPCs that is required for the proper generation of new neurons in the adult mouse brain. With the program proposed here I aim i) to investigate the nature and fate of lipids in NSPCs and to characterize the cell-cycle associated dynamics of lipid storage organelles using diverse tools incl. time-lapse confocal microscopy and lipidomics, ii) to analyse the role of lipid-associated signalling (e.g., post-translational modifications of proteins by palmitoylation) and their dependency on newly-synthesized fatty acids using candidate-based and unbiased strategies, iii) to test if enhancement of de novo lipogenesis in NSPCs is sufficient to increase neurogenesis and ameliorate disease symptoms in animal models of major depression, which may lead to the validation of a novel molecular target to treat neurogenesis-associated diseases, iv) to evaluate the role of fatty acid synthase (Fasn), the key enzyme of de novo lipogenesis, as a putative new mediator of human cognition by generating a mouse model of human disease and targeting human embryonic stem cells. The insights gained from the studies proposed here have the potential to substantially advance our understanding of adult NSPC biology, to identify a new molecular target to treat neurogenesis-associated disease, and to create a novel link between adult neurogenesis and cognitive dysfunction.
-