A ketogenic diet differentially affects neuron and astrocyte transcription

Ketogenic diets (KDs) alter brain metabolism. Multiple mechanisms may account for their effects, and different brain regions may variably respond. Here, we considered how a KD affects brain neuron and astrocyte transcription. We placed male C57Bl6/N mice on either a 3-month KD or chow diet, generated enriched neuron and astrocyte fractions, and used RNA-Seq to assess transcription. Neurons from KD-treated mice generally showed transcriptional pathway activation while their astrocytes showed a mix of transcriptional pathway suppression and activation. The KD especially affected pathways implicated in mitochondrial and endoplasmic reticulum function, insulin signaling, and inflammation. An unbiased analysis of KD-associated expression changes strongly implicated transcriptional pathways altered in AD, which prompted us to explore in more detail the potential molecular relevance of a KD to AD. Our results indicate a KD differently affects neurons and astrocytes, and provide unbiased evidence that KD-induced brain effects are potentially relevant to neurodegenerative diseases such as AD.