Anne-Liek van Deijk
The role of glial lipid metabolism in neuronal plasticity: towards dietary modulation of synaptic function
One of the main functions of astrocytes is their contribution to the modulation of synaptic transmission. It has been demonstrated that astrocytes act as lipid providers to neurons, at least in vitro. Previous research in our group has shown that deletion of the SREBP cleavage activated protein (SCAP), a gene required for cholesterol and fatty acid synthesis, in astrocytes in mice resulted in reduced levels of cholesterol and specific fatty acids in the whole brain. This resulted in brain hypotrophy, as well as defects in motor control and behavior. To overcome the reduced levels of lipids, SCAP mutant mice were exposed to a diet containing high levels of lipids, which significantly improved the survival as well as motor and behavioral function. This suggests that disrupted lipid synthesis in astrocytes may underlie prominent CNS neuropathologies and that lipid supplementation should be considered as therapeutic intervention when brain lipid metabolism is compromised.
This project focuses on neuron-astrocyte interactions at the tripartite synapse and how these are modulated by dietary lipid supplements. Since defective astrocyte function may interfere with nutritional support of neurons by astrocytes, dietary supplements may be a promising approach to bypass this defective nutritional support. For this purpose, we will make use of 1) in vitro co-cultures in which neurite outgrowth and synaptogenesis are strongly dependent on astrocyte factors, and 2) in vivo mouse models to determine the consequence of defective astrocyte function on synaptic function and the rescue of neurological phenotypes by dietary supplements.
With this project I hope to contribute to a better understanding of defective lipid metabolism in the brain and come up with an effective diet to overcome neurological deficits caused by reduced lipid levels.
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