Investigating executive function disparities in mice with PD utilizing the 5-CSRT paradigm

Abstract

Abstract This study is centered on the evaluation of executive functions (EFs) in a Parkinson's disease (PD) mouse model using the 5-Choice Serial Reaction Time Task (5-CSRT), with a specific focus on investigating the potential impact of lyso-phosphatidylcholine (LPC) on executive dysfunction in the pathogenesis of PD. The overarching goal is to establish a comprehensive framework and baseline for touch screen behavior analysis in PD model mice.The research encompassed the utilization of SNCA*A53T transgenic mice and C57BL/6J wild-type mice. A rigorous assessment of the motor ability and primary cognitive function of A53T mice was conducted to validate the qualification of the A53T-PD mouse model. Baseline performance metrics for touch screen behavioral experiments were meticulously explored through 5-CSRT for each cohort of mice. Furthermore, key indicators reflective of executive dysfunction in PD mice were meticulously evaluated using principal components analysis (PCA) and receiver operating characteristic (ROC) curve analysis.The findings of this study unveiled heightened α-syn expression and diminished tyrosine hydroxylase (TH) expression in the midbrain of A53T mice, signaling motor and primary cognitive dysfunction within the PD model. Notably, the 5-CSRT analysis divulged decreased accuracy and trace number, alongside an escalation in the number of punishments within the A53T group in comparison to the Control group. Moreover, the LPC group, MPTP group, and MPTP + LPC group all showcased impaired executive function, with the MPTP + LPC group demonstrating a more pronounced impairment relative to the Control group.In summation, this study established baseline accuracy levels for 5-CSRT in both wild-type and A53T mice, identified pivotal indicators of executive dysfunction, and underscored the potential of 5-CSRT in discerning drug-induced PD models. The implications of these findings suggest that intervention can be effectively administered once the baseline session accuracy reaches 80%. Ultimately, this study offers valuable insights into the evaluation of EFs in PD model mice and sheds light on the potential impact of LPC on executive dysfunction within the context of PD pathogenesis.