S-057 | Gene therapy with OSKM genes enhances hippocampal-dependent recognition memory

S-057 | Gene therapy with OSKM genes enhances hippocampal-dependent recognition memory 150 150 SAN 2024 Annual Meeting

Cognition, Behavior, and Memory
Author: Diana Camila Pasquini Pasquini | Email: dpasquini@med.unlp.edu.ar


Diana Camila Pasquini Pasquini, Magdalena Vicens, Manuel Ronco

NEURODEGENERATIVE DISEASES, INIBIOLP, UNLP

It is well established that aging is associated with a reduction in hippocampal neurogenesis, leading to memory impairment in mammals. To investigate therapies that reactivate neurogenesis, decrease neuroinflammation, and promote senolitic effect we performed an experiment on 66 rats divided into three age groups: young (6 months, n=28), middle-aged (12 months, n=25), and senescent (24 months, n=13).OSKM-treated rats in each age group received stereotaxic bilateral injection of an adenoviral vector harboring Yamanaka genes (OSKM) into the dentate gyrus of the hippocampus. Placebo control rats received an adenoviral vector carrying the GFP reporter protein gene. Intact control rats without intervention. At 40 days of post-treatment, the time require to restore neurogenesis, spontaneous location recognition (SLR) and Barnes maze tests were performed to evaluate the effects of OSKM factors. In the spontaneous location recognition rats tested under two choice conditions: Low and High overlapping condition designed by the new object location. Results showed that control placebo and intact cohorts do not discriminate the novel locations in the two conditions. Interestingly, OSKM-treated rats present a major preference for the novel location in the High condition in all age groups. This suggests that the SLR-behavioural protocol is not adequate for detect age-related cognitive decline. Furthermore, recognition memory in the High overlapping condition was enhanced by OSKM factors.

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