Hippocampal age-related DNA methylation and OSKM gene therapy for improvement of memory

CHIAVELLINI, PRISCILA; CANATELLI-MALLAT M; GALLARDO D; PASQUINI C; LEHMANN M; ZOLLER JA; CIPRIANO A; CLEMENT J; MOREL GR; SEBASTIANO V; HORVATH S; GOYA RG

Newry

Simposio; Gordon Research Conference; 2022

Gordon Research Conference

The aging of the central nervous system is associated with a progressive deterioration of spatial learning and memory. These functional alterations are correlated with morphological and molecular changes in the hippocampus. As a potential therapeutic target, we characterized the hippocampal aging at the DNA methylation level and its correlation with spatial memory which was assessed through the Barnes maze test.In initial studies, we implemented OSKM gene therapy using a polycistronic adenovector expressing OSKM and the reporter gene GFP. Learning and spatial memory performance were also assessed to test the effects of the OSKM gene expression on the cognition of the animals. Sprague-Dawley rats aged 2.6-month and 26.6 month were analyzed. OSKM-Ad was injected bilaterally in the subgranular zone in the Dentate Gyrus region of the hippocampus of 26 month-old rats. Four weeks after injection, we performed the Barnes maze test. A week after, the animals were sacrificed and the hippocampus stored properly for molecular and cellular analysis. DNA methylation assessment of each age group showed that the methylation of 7222 CpGs in the hippocampus changed with age (q-value