OSKM gene therapy to improve neurogenesis and age-associated cognitive decline in middle-aged rats

PASQUINI C; PERALTA F; GOMEZ MARTINEZ CD; REGGIANI PC; MOREL GR

San Luis

Congreso; Congreso SAN; 2023

Sociedad Argentina de Neurociencias

Central nervous system changes over time are associated with a progressive impairment ofspatial deterioration and memory. These functional alterations correlate with morphologicaland molecular changes in the hippocampus. As a potential therapeutic target, we characterizethe aging of the hippocampus at the level of spatial memory evaluated by the Barnes mazetest and object recognition test.In preliminary studies, we implemented OSKM gene therapy using a polycistronic adenovectorexpressing OSKM and the GFP reporter gene. Spatial learning and memory performance wasalso assessed to test the effects of OSKM gene expression on animal cognition (SLR).12-month-old Sprague-Dawley rats were tested. We evaluated the learning and memorycapacities of the animals through the Barnes Maze and SLR tests. Five days later, theanimals were perfused and the brain was removed for immunohistochemical tests.In the treatment OSKM was injected bilaterally into the subgranular zone of the hippocampaldentate gyrus region of 12-month-old rats. Four weeks after injection, we performed theBarnes maze test and the SLR. One week later, the animals were sacrificed and the brainstored appropriately for later analysis. Spatial memory performance was assessed with theBarnes maze test. To assess spatial memory retention, we assessed the time animals spent intarget sector 3 (GS3) when the escape box was removed.It was seen that the rats treated with the OSKM genes for cognitive impairment, showed abetter learning ability compared to the untreated ones, but their memory did not showsignificant differences In terms of object recognition, an improvement was also seen in thetreated rats compared to control.