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Content archived on 2024-05-14

The combination of gene targeting and biochip technology to study neurotrophin function during brain development

CORDIS provides links to public deliverables and publications of HORIZON projects.

Links to deliverables and publications from FP7 projects, as well as links to some specific result types such as dataset and software, are dynamically retrieved from OpenAIRE .

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The specific goal of this study is the regulation of the expression of brain derived neurotrophic factor (BDNF) after long term stimulation. Brain development is characterized by a spatiotemporally controlled sequence of cell migration, synaptogenesis and formation of topographic maps. Neurotrophins are likely to be instrumental during these processes, through major aspects remain to be unraveled. There is evidence that the survival and morphology of neurons can be influenced by neuronal activity. One member of the neurotrophin family, called brain derived neurotrophic factor, is responsible for activity dependant neuronal survival and differentiation. Short supra-physiological electrical stimulation as well as chemical induced depolarization by kainate level of BDNF mRNA in the brain is found in the hippocampus. In order to allow a molecular single cell analysis within this neuronal network under more physiological conditions, hippocampi slices will be organotypically cultured on micro electrode arrays (MEA with 60 electrodes). The MEA technique permits stimulation from a slice in different patterns from multiple sides for several weeks. Therefore, this method allows cultivation and simultaneous continuous electrical stimulation. To observe the activity regulated gene expression of BDNF over long term period, a fluorescent reporter gene (GFP) will be introduced into the mice genome at the BDNF locus. Consequently, activity induced BDNF expression can be monitored with confocal light scanning microscopy. The innovative technology of this project can be transferred into other sectors such as pharmaceutical industry: combination of chip, cell, and molecular facilitate in vitro evaluation of potential pharmaceuticals. The tissue MEA culture also offers an alternative to in vivo experimentation.

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