Hippocampal aging and regenerative therapy

MOREL GR

La Plata

Encuentro; Ibero ICSA meeting; 2023

Ibero ICSA

Changes in the central nervous system (CNS) over time are associated with progressive impairment in neurogenesis and synaptic connections, leading to cognitive deficits, specifically spatial and object recognition memory decline. In this study, our focus is on investigating the impact of gene therapy using the Yamanaka genes which consist of four transcription factors (OSKM: Oct4, Sox2, Klf4, and c-Myc) in the hippocampus of middle-aged rats and determine its eventual restorative effect on object recognition memory and spatial memory. An adenovector harboring the OSKM genes or GFP was bilaterally injected into the dentate gyrus of the hippocampus of the female Sprague-Dawley rats: Young (Y)= 17 months and Middle-aged (MA)= 13 months. Four weeks after the injection, the spontaneous location recognition (SLR) tests and Barnes maze (BM) were conducted.n spontaneous location recognition (SLR), the two groups have a preference for the new location of the object only in the high degree of overlap condition but the 12-month-old animals, treated with the OSKM genes in the DG of the hippocampus, have a greater preference for the new object compared to those treated with GFP.In the Barnes Maze, it was observed that the animals decreased their latency time with the trials (B), but there are no significant differences between the two groups. There was also no difference observed in latency in the probe trial between groups (C).On the other hand, the middle-aged rat has a deficit in object recognition memory (SLR) but maintains intact spatial memory (Barnes Maze).The female Sprague-Dawley (Y and MA) rat has a deficit in object recognition memory but maintains intact spatial memory.OSKM gene therapy in the DG of the hippocampus recovers object recognition memory only in the high-overlap condition in both groups (Y and MA)