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

Cognition, Behavior, and Memory

Author: Diana Camila Pasquini Pasquini | Email: dpasquini@med.unlp.edu.ar

Diana Camila Pasquini , Martina Canatteli , Priscila Chiavelini , Gustavo Morel

3° FCM

Changes in the central nervous system (CNS) over time are associated with a progressive deterioration in neurogenesis and synaptic connections, which generate loss of spatial memory, object recognition memory, lethargy, among other effects. of the aging of the CNS. These functional alterations correlate with morphological and molecular changes throughout the CNS. In this work we will focus on studying the hippocampus, a region of active neurogenesis, as a potential therapeutic target. We characterize aging at the level of spatial memory evaluated by the Barnes maze test and the object recognition test.

It is known that when the expression of four genes encoding four transcription factors, Oct4-Sox2-Klf4-c-Myc, is induced for a short period of time, cell identity can be maintained and, at the same time, reversal of marks. epigenetic characteristics associated with age (Horvat reference), observing a phenotype with less cognitive deterioration.

It was injected bilaterally into the subgranular zone of the dentate gyrus region of the hippocampus of 6 12-month-old rats. After performing the Barnes maze test and the SLR, it was found that the rats treated with the OSKM genes for cognitive impairment showed a better learning capacity compared to the untreated ones. Regarding object recognition, an improvement was also found in the treated rats.