Ketogenic diet administration later in life improves memory by modifying the synaptic cortical proteome via the PKA signaling pathway in aging mice
Aging adversely affects brain function, leading to cognitive decline. While a cyclic ketogenic diet (KD) has been shown to enhance memory in aged mice with prolonged use, its short-term effects later in life and the underlying molecular mechanisms are poorly understood. This study by Acuña-Catalán et al. (2024) investigates the impact of a short-term KD treatment initiated during the elderly stage on brain function in aged mice. Behavioral tests and long-term potentiation (LTP) recordings demonstrate that KD improves working memory and enhances hippocampal LTP. Moreover, analysis of synaptosome proteome in aged mice on long-term KD reveals significant changes primarily in the presynaptic compartment, particularly associated with the protein kinase A (PKA) signaling pathway. In vivo western blot analysis supports these findings, showing increased levels of brain-derived neurotrophic factor (BDNF) and phosphorylation of PKA substrates. In conclusion, the authors demonstrate that even short-term administration of KD modifies brain function in aged mice and mirrors molecular changes observed with long-term KD use, notably involving the PKA signaling pathway. These alterations promote synaptic plasticity in the advanced stages of life. [NPID: BDNF, LTP, PKA, aging, brain-derived neurotrophic factor, ketogenic diet, long-term potentiation, protein kinase A, proteomics, β-hydroxybutyrate]
Year: 2024
