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Bad Münster am Stein-Ebernburg, Germany

Schirmeier S.,Institute For Neuro Und Verhaltensbiologie | Klambt C.,Institute For Neuro Und Verhaltensbiologie
Mechanisms of Development | Year: 2015

The blood-brain barrier is an evolutionary ancient structure that provides direct support and protection of the nervous system. In all systems, it establishes a tight diffusion barrier that hinders uncontrolled paracellular diffusion into the nervous system. In invertebrates, the blood-brain barrier separates the nervous system from the hemolymph. Thus, the barrier-forming cells need to actively import ions and nutrients into the nervous system. In addition, metabolic or environmental signals from the external world have to be transmitted across the barrier into the nervous system. The first blood-brain barrier that formed during evolution was most likely based on glial cells. Invertebrates as well as primitive vertebrates still have a purely glial-based blood-brain barrier. Here we review the development and function of the barrier forming glial cells at the example of Drosophila. © 2015 Elsevier Ireland Ltd.

Volkenhoff A.,Institute For Neuro Und Verhaltensbiologie | Weiler A.,Institute For Neuro Und Verhaltensbiologie | Letzel M.,University of Munster | Stehling M.,MPI fur Molekulare Biomedizin | And 2 more authors.
Cell Metabolism | Year: 2015

Neuronal information processing requires a large amount of energy, indicating that sugars and other metabolites must be efficiently delivered. However, reliable neuronal function also depends on the maintenance of a constant microenvironment in the brain. Therefore, neurons are efficiently separated from circulation by the blood-brain barrier, and their long axons are insulated by glial processes. At the example of the Drosophila brain, we addressed how sugar is shuttled across the barrier to nurture neurons. We show that glial cells of the blood-brain barrier specifically take up sugars and that their metabolism relies on glycolysis, which, surprisingly, is dispensable in neurons. Glial cells secrete alanine and lactate to fuel neuronal mitochondria, and lack of glial glycolysis specifically in the adult brain causes neurodegeneration. Our work implies that a global metabolic compartmentalization and coupling of neurons and glial cells is a conserved, fundamental feature of bilaterian nervous systems independent of their size. © 2015 Elsevier Inc.

Schirmeier S.,Institute For Neuro Und Verhaltensbiologie | Matzat T.,Institute For Neuro Und Verhaltensbiologie | Klambt C.,Institute For Neuro Und Verhaltensbiologie
Brain Research | Year: 2015

Neuronal function requires constant working conditions and a well-balanced supply of ions and metabolites. The metabolic homeostasis in the nervous system crucially depends on the presence of glial cells, which nurture and isolate neuronal cells. Here we review recent findings on how these tasks are performed by glial cells in the genetically amenable model organism Drosophila melanogaster. Despite the small size of its nervous system, which would allow diffusion of metabolites, a surprising division of labor between glial cells and neurons is evident. Glial cells are glycolytically active and transfer lactate and alanine to neurons. Neurons in turn do not require glycolysis but can use the glially provided compounds for their energy homeostasis. Besides feeding neurons, glial cells also insulate neuronal axons in a way similar to Remak fibers in the mammalian nervous system. The molecular mechanisms orchestrating this insulation require neuregulin signaling and resemble the mechanisms controlling glial differentiation in mammals surprisingly well. We hypothesize that metabolic cross talk and insulation of neurons by glial cells emerged early during evolution as two closely interlinked features in the nervous system. This article is part of a Special Issue entitled SI: Myelin Evolution. © 2015 Elsevier B.V.

Sasse S.,Institute For Neuro Und Verhaltensbiologie | Neuert H.,Institute For Neuro Und Verhaltensbiologie | Klambt C.,Institute For Neuro Und Verhaltensbiologie
Wiley Interdisciplinary Reviews: Developmental Biology | Year: 2015

Glial cells are important constituents of the nervous system and a hallmark of these cells are their pronounced migratory abilities. In Drosophila, glial lineages have been well described and some of the molecular mechanisms necessary to guide migrating glial cells to their final target sites have been identified. With the onset of migration, glial cells are already specified into one of five main glial cell types. The perineurial and subperineurial glial cells are eventually located at the outer surface of the Drosophila nervous system and constitute the blood-brain barrier. The cortex glial cells ensheath all neuroblasts and their progeny and reside within the central nervous system. Astrocyte-like cells invade the neuropil to control synaptic function and ensheathing glial cells encase the entire neuropil. Within the peripheral nervous system, wrapping glial cells ensheath individual axons or axon fascicles. Here, we summarize the current knowledge on how differentiation of glial cells into the specific subtypes is orchestrated. Furthermore, we discuss sequencing data that will facilitate further analyses of glial differentiation in the fly nervous system. © 2015 Wiley Periodicals, Inc.

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