The role of oligodendroglial exosome secretion in axon-glia communication, glial support, and maintenance of axonal integrity

• Applicant: Professorin Dr. Eva-Maria Krämer-Albers
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2012 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 217173479

• Final Report Year: 2023

Final Report Abstract

Oligodendrocytes form the myelin sheath around axons and provide essential support required for the long-term integrity of axons. Lack of this support causes axons to degenerate in the course of neurodegenerative diseases and aging. This research project revealed that extracellular vesicles (i.e. exosomes) are an essential component of glial support. In addition, the detailed mechanisms of action were explored. Triggered by neuronal activity, oligodendroglial exosomes deliver bioactive molecules and activate signalling pathways that promote axonal energy homeostasis and help neurons to manage stressful conditions. The specific exosome cargo increases mitochondrial ATP generation, provides antioxidant defence, and promotes axonal transport. Mice with compromised oligodendroglial exosome release and function develop secondary axonal degeneration. In conclusion, exosome transfer from oligodendrocytes to neurons is essential for axon maintenance and complements metabolic support of axons by energy-rich metabolites. A comprehensive understanding of how oligodendrocytes sustain axons is pivotal to the development of therapeutic interventions to combat axonal degeneration in various neurodegenerative diseases, such as multiple sclerosis.

Publications

• Delivery on call: exosomes as “care packages” from glial cells for stressed neurons. e-Neuroforum, 19(4), 85-91.
  Krämer-Albers, E.-M. & Frühbeis, C.
  
• Extracellular vesicles as mediators of neuron-glia communication. Frontiers in Cellular Neuroscience, 7(2013).
  Frühbeis, Carsten; Fröhlich, Dominik; Kuo, Wen Ping & Krämer-Albers, Eva-Maria
  
• Lieferung auf Abruf: Exosomen als „Care“-Pakete von Gliazellen für gestresste Neurone. e-Neuroforum, 19(4), 146-155.
  Krämer-Albers, Eva-Maria & Frühbeis, Carsten
  
• Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte–Neuron Communication. PLoS Biology, 11(7),e1001604.
  Frühbeis, Carsten; Fröhlich, Dominik; Kuo, Wen Ping; Amphornrat, Jesa; Thilemann, Sebastian; Saab, Aiman S.; Kirchhoff, Frank; Möbius, Wiebke; Goebbels, Sandra; Nave, Klaus-Armin; Schneider, Anja; Simons, Mikael; Klugmann, Matthias; Trotter, Jacqueline & Krämer-Albers, Eva-Maria
  
• Multifaceted effects of oligodendroglial exosomes on neurons: impact on neuronal firing rate, signal transduction and gene regulation. Philosophical Transactions of the Royal Society B: Biological Sciences, 369(1652), 20130510.
  Fröhlich, Dominik; Kuo, Wen Ping; Frühbeis, Carsten; Sun, Jyh-Jang; Zehendner, Christoph M.; Luhmann, Heiko J.; Pinto, Sheena; Toedling, Joern; Trotter, Jacqueline & Krämer-Albers, Eva-Maria
  
• Biological properties of extracellular vesicles and their physiological functions. Journal of Extracellular Vesicles, 4(1).
  Yáñez‐Mó, María; Siljander, Pia R.‐M.; Andreu, Zoraida; Bedina Zavec, Apolonija; Borràs, Francesc E.; Buzas, Edit I.; Buzas, Krisztina; Casal, Enriqueta; Cappello, Francesco; Carvalho, Joana; Colás, Eva; Cordeiro‐da Silva, Anabela; Fais, Stefano; Falcon‐Perez, Juan M.; Ghobrial, Irene M.; Giebel, Bernd; Gimona, Mario; Graner, Michael; Gursel, Ihsan; ... & De Wever, Olivier
  
• Extracellular Vesicles: Goodies for the Brain?. Neuropsychopharmacology, 41(1), 371-372.
  Krämer-Albers, Eva-Maria & Ping Kuo-Elsner, Wen
  
• Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 7(1):1535750
  Théry, C; Witwer, KW; Aikawa, E; Krämer-Albers, E. M.; Zocco, D & Zuba-Surma, EK
  
• Serum‐free media supplements carry miRNAs that co‐purify with extracellular vesicles. Journal of Extracellular Vesicles, 8(1).
  Auber, Martin; Fröhlich, Dominik; Drechsel, Oliver; Karaulanov, Emil & Krämer‐Albers, Eva‐Maria
  
• Extracellular vesicles in the oligodendrocyte microenvironment. Neuroscience Letters, 725(2020, 4), 134915.
  Krämer-Albers, Eva-Maria
  
• Oligodendrocytes Provide Antioxidant Defense Function for Neurons by Secreting Ferritin Heavy Chain. Cell Metabolism, 32(2), 259-272.e10.
  Mukherjee, Chaitali; Kling, Tina; Russo, Belisa; Miebach, Kerstin; Kess, Eva; Schifferer, Martina; Pedro, Liliana D.; Weikert, Ulrich; Fard, Maryam K.; Kannaiyan, Nirmal; Rossner, Moritz; Aicher, Marie-Louise; Goebbels, Sandra; Nave, Klaus-Armin; Krämer-Albers, Eva-Maria; Schneider, Anja & Simons, Mikael
  
• Oligodendrocytes support axonal transport and maintenance via exosome secretion. PLOS Biology, 18(12),e3000621.
  Frühbeis, Carsten; Kuo-Elsner, Wen Ping; Müller, Christina; Barth, Kerstin; Peris, Leticia; Tenzer, Stefan; Möbius, Wiebke; Werner, Hauke B.; Nave, Klaus-Armin; Fröhlich, Dominik & Krämer-Albers, Eva-Maria
  
• Was hält Neuronen fit? Kommunikation zwischen Hirnzellen. Buchbeitrag „Was hält uns jung?“ Hrsg. Helmut Fink, Rainer Rosenzweig ISBN 978-3-948787-01-1 (Print), ISBN 978-3-948787-02-8 (E-Book)
  Albers, E.M.
  
• “Brainstorming”: Extracellular Vesicles in Physical Activity and Neuronal Health. Trillium Exctracellular Vesicles, 2(1), 54-59.
  Brahmer, Alexandra & Krämer-Albers, Eva-Maria
  
• Extracellular Vesicles in neural cell interaction and CNS homeostasis. FASEB BioAdvances, 3(8), 577-592.
  Schnatz, Andrea; Müller, Christina; Brahmer, Alexandra & Krämer‐Albers, Eva‐Maria
  
• The power of imaging to understand extracellular vesicle biology in vivo. Nature Methods, 18(9), 1013-1026.
  Verweij, Frederik J.; Balaj, Leonora; Boulanger, Chantal M.; Carter, David R. F.; Compeer, Ewoud B.; D’Angelo, Gisela; El Andaloussi, Samir; Goetz, Jacky G.; Gross, Julia Christina; Hyenne, Vincent; Krämer-Albers, Eva-Maria; Lai, Charles P.; Loyer, Xavier; Marki, Alex; Momma, Stefan; Nolte-‘t Hoen, Esther N. M.; Pegtel, D. Michiel; Peinado, Hector; Raposo, Graça; ... & van Niel, Guillaume
  
• Mechanisms of axonal support by oligodendrocyte-derived extracellular vesicles. Nature Reviews Neuroscience, 24(8), 474-486.
  Krämer-Albers, Eva-Maria & Werner, Hauke B.