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Frank W. Pfrieger"Synapses, glia and cholesterol : what is it all about?".

Abstract :


The formation of chemical synaptic connections between neurons is a critical phase during brain development and plays an important role in learning and memory. Up to now, however, the mechanisms of this fascinating process are poorly understood. Our study (Mauch et al., 2001) suggests a link between synaptogenesis and cholesterol and an obligatory dependence of neurons on astrocyte-derived cholesterol (Pfrieger, 2003). In my talk I will provide an update on the following research projects in our lab.

1. How does cholesterol enhance synaptogenesis? There are different ways how cholesterol can enhance the number and efficacy of synapses: It may act as a synaptogenic signal, for example after conversion to a steroid, it may serve as building material for synaptic components, or it may allow for the formation of microdomains (rafts) and thus enhance cellular processes that are essential for synaptogenesis. We are currently testing these hypotheses in our culture preparation of highly purified neurons using electrophysiological recordings and fluorescence imaging.

2. Do all CNS neurons depend on glia-derived cholesterol? Our finding that synaptogenesis in rat retinal ganglion cells depends on external cholesterol raises the question whether this also applies to other types of CNS neurons. So far, we cannot address this question, since there are no methods available to isolate neurons from postnatal brain to a sufficiently high degree and to cultivate them under defined, glia-free conditions. In this project, we are trying to establish such methods for neurons from different regions of the mouse CNS. These new cultures should allow us to study a wide range of glia-neuron and glia-synapse interactions in normal
and transgenic animals.
3. How do neurons maintain their cholesterol level? The idea that neurons depend on glia-derived cholesterol raises general questions concerning cholesterol homeostasis in CNS neurons. Despite the intense research on cholesterol, surprisingly little is known about this topic except that cholesterol metabolism in brain and blood are clearly separated. As a first approach, we study different aspects of cholesterol homeostasis, namely synthesis, release and uptake, in glia-free cultures of neurons from postnatal rodents using a variety of methods including radioactive labeling and thin-layer chromatography.

 

IFR