Institute of Pharmacology and Toxicology
University of Zurich
Tel. +41 44 635 6085
Secr. Tel. +41 44 635 5969
Our group uses a wide range of imaging tools to study the cell-to-cell communication pathways involved in energy metabolism and information processing in cerebral cortex. Furthermore, we are working on dissecting the interaction of neurons and astrocytes with the vascular system, which is responsible for maintaining adequate delivery of oxygen and energy substrates to the brain. As well as studying these systems, the development of imaging systems for in vivo research is an additional research focus of the group.
1 professor, 6 postdocs, 6 doctoral students, 1 administrative person
For details, please see: http://www.pharma.uzh.ch/research/functionalimaging.html
The brain relies on a continuous energy supply. Under normal circumstances, glucose represents the main energy substrate for the brain. Although the brain constitutes only 2% of the body weight, the energy-consuming processes of the brain account for about 25% of total body glucose utilization. In total, the human brain of an adult burns approximately 120 gram of glucose during a whole day.
For decades the notion that glucose is taken up and metabolized by individual brain cells according to their relative need was carved in stone. However, twenty years ago, a novel concept was introduced. The so-called astrocyte-neuron lactate shuttle hypothesis postulates main glucose uptake by astrocytes – brain cells located between neurons and blood vessels. Only after glycolytic degradation, lactate is transported to neurons where it serves as an energy substrate.
Past in vivo studies did not have the capability to resolve aspects of brain energy metabolism on a sufficient temporal and spatial level. As a consequence, the validity of the model has not been unambiguously demonstrated yet.
Recently, we established the combined use of genetically encoded substrate sensors and two-photon laser scanning microscopy in the intact brain. This toolset allows real-time measurements of substrate concentrations (e.g. glucose, lactate, pyruvate) in individual cellular compartments.
At present, we focus mainly on the following questions:
A more complete understanding of the mechanisms and compartments involved in brain energetics is fundamental for a full understanding not only of the physiology but also the pathophysiology of brain function. Indeed, many neurological pathologies such as neurodegenerative diseases, stroke, epilepsy, migraine and brain tumors display abnormalities in brain energy metabolism.
Optical imaging: in-vivo two-photon microscopy, multiwavelength spectroscopy, laser speckle contrast imaging, voltage sensitive dye imaging
Radiotracer research: Quantitative measurements of radiotracer kinetics using PET and beta-probes
Electrophysiology: Acute and chronic multichannel extracellular recordings
Vascular anatomy: Immunohistochemistry, corrosion casts, synchrotron-based x-ray microscopy
Modeling: Multiscale modeling of fluid dynamics of cerebral blood flow
BIO 402, BIO 405
Advanced Courses in Neurosciences (ZNZ PhD program)
Swiss National Science Foundation, SystemsX.ch, OPO Stiftung, ZIHP, Forschungskredit UZH, EMBO, Canadian Heart and Stroke Foundation
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