S-062 | Gene therapy with OSKM genes improves hippocampus-dependent episodic memory

S-062 | Gene therapy with OSKM genes improves hippocampus-dependent episodic memory 150 150 SAN 2024 Annual Meeting

Cognition, Behavior, and Memory
Author: Manuel Andres Ronco | Email: maroncoescuela@gmail.com


Magdalena Vicens, Diana Camila Pasquini, Manuel Andres Ronco

NEURODEGENERATIVE DISEASES, INIBIOLP, UNLP

Changes in the central nervous system (CNS) over time are associated with a progressive deterioration of neurogenesis and synaptic connections, leading to cognitive deficits, specifically loss of spatial memory and loss of recognition memory. objects. These functional alterations correlate with morphological and molecular changes throughout the CNS, mainly in the hippocampus. In this study, we aim to investigate the impact of gene therapy using Yamanaka genes (Oct4, Sox2, Klf4 and c-Myc) on the hippocampus of middle-aged rats. Our hypothesis is that the expression of these genes that encode four transcription factors, when expressed for a short period, allows the maintenance of cellular identity and the simultaneous reversal of age-associated epigenetic marks (Horvat reference), promoting neurogenesis in the hippocampus.
In the treatment, an adenovector carrying OSKM genes was injected bilaterally into the subgranular zone of the dentate gyrus region of the hippocampus in 62 rats aged 6, 12, and 24 months. Four weeks later, the Barnes maze and SLR tests were performed. To determine spatial memory retention in the Barnes maze, we assessed the time animals spent in target sector 3 (GS3) when the escape box was removed.
It will be observed that rats treated with the OSKM genes will demonstrate better learning ability compared to the untreated group (Barnes maze). Regarding object recognition, an improvement will also be observed with bilateral OSKM treatment in the subgranular

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