Analysis of the supportive role of glial cells in nutrient homeostsis of the Drosophila brain

• Applicant: Professorin Dr. Stefanie Schirmeier
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 214909443

• Final Report Year: 2015

Final Report Abstract

The nervous system consumes large amounts of energy that need to be efficiently delivered. Since neuronal function also depends on a strictly controlled extracellular milieu, neurons are well separated from circulation by the blood-brain barrier. This, in turn, necessitates efficient ways of supplying nutrients, which means strictly regulated transport. During the funding period I addressed the question how carbohydrates are shuttled into the nervous system to satisfy the high neuronal energy demand. I worked closely with two PhD students and we were able to show that carbohydrates are specifically taken up by the outer surface glial layer, the perineurial glial cells. This, for the first time, assigns a function to this cell type: nurturing the brain. We also found that glial metabolism relies on glycolysis, which, surprisingly, is dispensable in neurons. Moreover, glial glycolysis is essential for neuronal survival. The glial cells secrete alanine and lactate, which are both taken up and metabolized by neurons. Our results indicate that a metabolic division of labor, similar to that proposed for the mammalian nervous system, takes place in Drosophila. Therefore, it seems that such a compartmentalization is not just a feature of the tripartite synapse and long myelinated axons, but rather a global concept that developed early in the evolution of complex nervous systems.

Publications

• (2014). Closing the gap between glia and neuroblast proliferation. Developmental Cell 30, 249–250
  Limmer, S., and Klämbt, C.
  
• (2014). The Drosophila blood-brain barrier: development and function of a glial endothelium. Front Neurosci 8, 365
  Limmer, S., Weiler, A., Volkenhoff, A., Babatz, F., and Klämbt, C.
  
• (2015), Glial glycolysis is essential for neuronal survival in Drosophila. Cell Metabolism Volume 22, Issue 3, 1 September 2015, Pages 437-447
  Volkenhoff, A., Weiler, A., Letzel, M., Stehling, M., Klämbt, C. and Schirmeier, S.
  
• (2015), The Drosophila blood-brain-barrier as interface between neurons and hemolymph, Mechanisms of Development
  Schirmeier, S., Klämbt, C.