1. Ketogenic diet administration later in life improves memory by modifying the synaptic cortical proteome via the PKA signaling pathway in aging mice.
- Author
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Acuña-Catalán D, Shah S, Wehrfritz C, Nomura M, Acevedo A, Olmos C, Quiroz G, Huerta H, Bons J, Ampuero E, Wyneken U, Sanhueza M, Arancibia F, Contreras D, Cárdenas JC, Morales B, Schilling B, Newman JC, and González-Billault C
- Subjects
- Animals, Mice, Male, Mice, Inbred C57BL, Hippocampus metabolism, Synapses metabolism, Brain-Derived Neurotrophic Factor metabolism, Neuronal Plasticity physiology, Phosphorylation, Cyclic AMP-Dependent Protein Kinases metabolism, Aging physiology, Aging metabolism, Signal Transduction, Diet, Ketogenic methods, Proteome metabolism, Memory physiology, Long-Term Potentiation physiology
- Abstract
Aging compromises brain function leading to cognitive decline. A cyclic ketogenic diet (KD) improves memory in aged mice after long-term administration; however, short-term effects later in life and the molecular mechanisms that govern such changes remain unclear. Here, we explore the impact of a short-term KD treatment starting at elderly stage on brain function of aged mice. Behavioral testing and long-term potentiation (LTP) recordings reveal that KD improves working memory and hippocampal LTP. Furthermore, the synaptosome proteome of aged mice fed a KD long-term evidence changes predominantly at the presynaptic compartment associated to the protein kinase A (PKA) signaling pathway. These findings were corroborated in vivo by western blot analysis, with high BDNF abundance and PKA substrate phosphorylation. Overall, we show that a KD modifies brain function even when it is administered later in life and recapitulates molecular features of long-term administration, including the PKA signaling pathway, thus promoting synaptic plasticity at advanced age., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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