The ketogenic diet as an epigenetic modulator

STUPNIKI S.; RÍAS E.; DIONISIO L.; BAIER C.J.; SPITZMAUL G.

San Luis

Congreso; SAN 2023 Meeting; 2023

Sociedad Argentina de Investigación en Neurociencias

The ketogenic diet (KD) is high in fat and very low in carbohydrates, leading to ketonebodies synthesis. They serve not only as an alternative energy source but also asepigenetic modulators. We administered the KD to B6 mice from P21 to P80, alongside acontrol group that was fed a regular diet. Behavioral tests were conducted to evaluatethe effects of KD on sociability, recognition memory, and anxiety-like behavior. Weobtained mRNA from hippocampus to evaluate gene expression related to neuronalexcitability regulation (Kcnq2), oxidative stress (Foxo3, Sod2, Sod1) and memoryprocessing (Chrna7). KD mice exhibited increased sociability. They showed a lowerexploratory ratio during the NOR test, indicating a short-term recognition memoryimpairment. In the open field, KD mice displayed increased thigmotaxis, suggestingelevated anxiety-like behavior. In KD mice, Sod1 and Sod2 expression significantlyincreased, while and Kcnq2 and Chrna7 decreased. Our results suggest that alteredChrna7 expression due to KD may play a role in the observed impairment in the shorttermrecognition memory. The upregulation of Sod1 and Sod2 highlight KD´s potentialrole modulating oxidative stress pathways. Changes in Kcnq2 expression couldmodulate neuronal excitability. Coupled with increased antioxidant enzyme expression,this could contribute to the diet’s neuroprotective effects and possibly underlie itstherapeutic potential in ASD and epilepsy.