Rapamycin Improves Motor Behavior and Sociability but Impairs Memory in NS-Pten Knockout Mice
Abstract number :
3.059
Submission category :
1. Basic Mechanisms / 1E. Models
Year :
2021
Submission ID :
1825899
Source :
www.aesnet.org
Presentation date :
12/6/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:51 AM
Authors :
David Narvaiz, BS - Baylor University; Suzanne Nolan-Strle - Vanderbilt University; Andrew Holley - UT Southwestern; Greg Smith - David Geffen School of Medicine - UCLA; Conner Reynolds - UNT Health Science Center; Meagan Volquardsen - Psychology and Neuroscience - Baylor University; Katherine Blandin - Psychology and Neuroscience - Baylor University; Dexter Nguyen - Psychology and Neuroscience - Baylor University; Doan Tran - Psychology and Neuroscience - Baylor University; Joaquin Lugo - Associate Professor & Director, Psychology and Neuroscience, Baylor University
Rationale: The mammalian target of rapamycin (mTOR) is critical for proper brain growth and development. Genetic mutations to phosphatase and tensin homolog deleted on chromosome ten (PTEN) – a negative regulator of mTOR – produces hyperactive mTOR signaling followed by neuronal hypertrophy and a progressive development of seizures. In both mice and humans, PTEN mutations can also cause intellectual disabilities, developmental delays, and autistic-like behaviors. Rapamycin, an mTOR inhibitor, has been shown to reverse neuronal hypertrophy and reduce seizures in neuronal subset specific Pten knockout (KO) mice. While KO mice also demonstrate impaired memory, social and motor deficits, the impact of mTOR inhibition on the development of these behavioral deficits has not been determined in this model.
Methods: KO and wildtype (WT) mice were administered 10 mg/kg of rapamycin for 10 days beginning at postnatal day 28. Treatment and control groups were then subjected to the following behavioral test battery to determine the impact of mTOR inhibition on behavior: open field, elevated plus maze, marble burying, social chamber, and trace fear conditioning.
Results: KO mice administered rapamycin demonstrated improved marble burying compared to KO controls, p < .05. Rapamycin also increased sociability in all groups, p < .05. While mTOR inhibition had no impact on cued fear memory, p = .49, it reduced contextual fear memory in all groups, p < .05. Rapamycin had no impact on anxiety like behavior in the elevated plus maze and resulted in an overall, general reduction in activity in the open field.
Basic Mechanisms