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Cell Rep Med ; 5(6): 101593, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38843842

RESUMEN

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.


Asunto(s)
Envejecimiento , Proteínas Quinasas Dependientes de AMP Cíclico , Dieta Cetogénica , Potenciación a Largo Plazo , Memoria , Proteoma , Transducción de Señal , Animales , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Envejecimiento/fisiología , Envejecimiento/metabolismo , Dieta Cetogénica/métodos , Proteoma/metabolismo , Ratones , Masculino , Memoria/fisiología , Potenciación a Largo Plazo/fisiología , Ratones Endogámicos C57BL , Hipocampo/metabolismo , Sinapsis/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Plasticidad Neuronal/fisiología , Fosforilación
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