NGFN-PLUS

Glutamatergic and epigenetic profiling with microarrays

Coordinator:    Prof. Dr. Peter J. Gebicke-Haerter
Institution: ZI Mannheim
Homepage: www.zi-mannheim.de/267
The most extensively investigated neurotransmitter system in addiction research has been the dopaminergic system. Recently, the glutamatergic system has gained increased interest, because it tightly interacts with the dopaminergic system and with additional systems like the GABA-ergic and the opioid systems. In this light, the project wants to study changes of molecular interactions in brains of animals devoid of or overexpressing genes of the glutamate system under the influence of alcohol. Gene chips containing fractions (oligonucleotides) of 750 selected genes belonging to the glutamate system are being used for analyses of transcripts obtained from various murine brain regions at different time points during development of the animals. The identified, differentially expressed genes will then be subjected to analyses by epigenetic chips that search for changes of methylation patterns. Owing to the scheduled series of time-course experiments, the results will provide detailed insights into alcohol-dependent regulation of glutamate-associated genes during the development of the brain and the function of a few selectively overexpressed or knocked down genes in those conditions.
The gene patterns will be used in computer simulations to identify pivotal molecular bifurcations and time points where the drug forces apart controls from alcohol-treated ones.
Eventually, the results will be used to evaluate their significance for new or improved treatment strategies in human alcoholic patients.


                    
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