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A ketogenic diet differentially affects neuron and astrocyte transcription
Author(s) -
Koppel Scott J.,
Pei Dong,
Wilkins Heather M.,
Weidling Ian W.,
Wang Xiaowan,
Menta Blaise W.,
PerezOrtiz Judit,
Kalani Anuradha,
Manley Sharon,
Novikova Lesya,
Koestler Devin C.,
Swerdlow Russell H.
Publication year - 2021
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.15313
Subject(s) - astrocyte , neuron , biology , transcription factor , transcription (linguistics) , microbiology and biotechnology , signal transduction , neurodegeneration , transcriptional regulation , endocrinology , neuroscience , medicine , central nervous system , biochemistry , gene , linguistics , philosophy , disease
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.