Project description:To maintain homeostasis, the body including the brain reprograms its metabolism in response to altered nutrition or disease. However, the consequences of these challenges for the energy metabolism of the different brain cell types remain unknown. Here, we generated a proteome atlas of the major CNS cell types from young and adult mice, after feeding the therapeutically relevant low-carbohydrate, high-fat ketogenic diet (KD) and during neuroinflammation. Under steady-state conditions, CNS cell types prefer distinct modes of energy metabolism. Surprisingly, the comparison with KD revealed distinct cell type-specific strategies to manage the altered availability of energy metabolites. Astrocytes and neurons but not oligodendrocytes demonstrated metabolic plasticity. Unexpectedly, inflammatory demyelinating disease changed the neuronal metabolic signature in a similar direction as KD. Together, these findings highlight the importance of the metabolic crosstalk between CNS cells and between the periphery and the brain to manage altered nutrition and neurological disease.
Project description:To maintain homeostasis, the body including the brain reprograms its metabolism in response to altered nutrition or disease. However, the consequences of these challenges for the energy metabolism of the different brain cell types remain unknown. Here, we generated a proteome atlas of the major CNS cell types from young and adult mice, after feeding the therapeutically relevant low-carbohydrate, high-fat ketogenic diet (KD) and during neuroinflammation. Under steady-state conditions, CNS cell types prefer distinct modes of energy metabolism. Surprisingly, the comparison with KD revealed distinct cell type-specific strategies to manage the altered availability of energy metabolites. Astrocytes and neurons but not oligodendrocytes demonstrated metabolic plasticity. Unexpectedly, inflammatory demyelinating disease changed the neuronal metabolic signature in a similar direction as KD. Together, these findings highlight the importance of the metabolic crosstalk between CNS cells and between the periphery and the brain to manage altered nutrition and neurological disease.
Project description:To understand the transcriptional effect of fasting and feeding a ketogenic diet on mouse CNS astrocytes, we performed translating ribosomal affinity purification (TRAP) of mRNAs immunoprecipitated from hippocampus. TRAP mice express a ribosomal epitope tag upon Cre-induced recombination that can be immunoprecipitated following activation. We measured the abundance of actively translating mRNAs from a ribosomal pull-down that came from adult astrocyte (Aldh1l1-Cre)-specific TRAP mice that were subjected to one of three dietary conditions: four weeks of normal chow diet, four weeks of ketogenic diet (high-fat, low-carbohydrate)43, or an 18-hour fast. Immediately following the respective diets, forebrain and hippocampus was harvested from all groups, ribosomes were immunoprecipitated, and actively translating mRNAs in the ribosomes were purified.
Project description:The ketogenic diet has long been used to treat epilepsy, but its mechanism is not yet clearly understood. To explore the potential mechanism, the changes in gene expression induced by the ketogenic diet in the rat kainic acid (KA) epilepsy model were analyzed. Two-condition experiment, Normal diet-fed rat brain vs. Ketogenic diet-fed rat brain. Duplicate per array
Project description:Specific pathogen free wild-type C57Bl/6 male mice fed ketogenic diet (Bio-Serv AIN-76-A) for 4 weeks Keywords: RNA Expression Array Hearts from 12 week-old mice that were maintained on a standard polysacchardide-rich chow until the age of 8 weeks, at which time they were switched to a ketogenic diet (ad libitum) and maintained for 4 additional weeks prior to collection of tissues
Project description:The ketogenic diet has long been used to treat epilepsy, but its mechanism is not yet clearly understood. To explore the potential mechanism, the changes in gene expression induced by the ketogenic diet in the rat kainic acid (KA) epilepsy model were analyzed.