The brain is a fascinating organ. It is one of the metabollically most active organs of the human body. Although the brain contributes only up to 2% to the body mass, about 20% of the glucose and the oxygen consumed by the body are used in the human brain, mainly to support energy-requiring membrane transport processes. The brain is a complex organ that contains in addition to neurons a variety of glial cell types. Among these, astrocytes and oligodendrocytes, the so-called macroglial cells, are well known for their functions in neuronal support as well as in synapse and myelin formation. In addition, the brain contains also microglial cells in substantial numbers, the neuroprotective immunocompetent cells in the central nervous system. All types of brain cells fulfill special and essential functions in the brain.

Suppy of GSH precursors from astrocytes to neurons

The brain is one of the most metabolically active organs of the human body. In addition to an extensive glucose metabolism, an intense amino acid metabolism occurs in brain due to protein turnover and the synthesis and degradation of amino acids and amino acid-derived neurotransmitters. Due to cell type compartimentation of metabolic pathways energy is not wasted by equiping every brain cell type with every metabolic pathway. However, the loss of independence is the price the different cell types in the brain have to pay for a close coupling due to specialization for different functions. During the last two decades evidence is growing that an intensive metabolic exchange occurs between the different types of brain cells. The dependence of neurons on metabolites of astrocytes strongly suggest a metabolic cooperation between the neighboring cell types of the brain rather than competition of these cell types for extracellular substrates. Strong evidence on metabolite trafficking between astrocytes and neurons has been obtained for the metabolism of carbohydrates and amino acids as well as for the defense against xenobiotics and oxidative stress. A good example for a metabolic interaction between astrocytes and neurons is the supply of neurons by astrocytes with precursors for the synthesis of the protective tripeptide glutathione (GSH).

We investigate basal mechanisms of the metabolism of the individual types of brain cells, the metabolic interactions that take place between different types of brain cells, the mechanisms involved in the defence of brain cells against oxidative stress and toxins as well as the handling of nanoparticles by brain cells. As model systems for these studies we are using primary and secondary cell cultures of the four most important brain cell types (neurons, astrocytes, oligodendrocytes, microglial cells). Aim of our studies is to improve the understanding of metabolic processes in brain and to find the molecular basis for disturbances in brain metabolism that have been reported for neurological disorders. This knowledge will be used to develop new neuroprotective strategies against oxidative stress, drugs and environmental toxins.

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