097 | Examining the influence of the Cdk5/p35 Complex on Working Memory and the Effects of Methylphenidate Treatment in an ADHD Mouse Model

Cognition, Behavior, and Memory

Author: Florencia Dadam | Email: fdadam@unc.edu.ar

Florencia Dadam , Martin Basmadjian , Eugenia Sosa , Daiana Solorzano , Anahi Rodriguez , María Soledad Miró , Sebastián Leonangeli , María Gabriela Paglini

1° Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-UNC.
2° Instituto de Virología “Dr. José María Vanella” , In.Vi.V.-CONICET-UNC.
3° Centro de Investigaciones en Bioquímica Clínica e Inmunología CIBICI-CONICET-UNC

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental condition characterized by symptoms of hyperactivity, impulsivity, and memory deficits. The treatment of ADHD includes the use of psycho-stimulants, such as methylphenidate (MTPH). One of the crucial symptoms of ADHD is working memory (WM) impairment that is defined as a short-term memory used for the planning and execution of cognitive functions. Transgenic mice lacking p35 (p35KO), the activating subunit of Cdk5 present key hallmarks of ADHD animal models..Cdk5/p35 complex regulates neuronal survival, dopaminergic neurotransmission and synaptic plasticity among others.
Given that, we aimed to study the contribution of the Cdk5/p35 complex to WM and explore the impact of MTPH treatment, taking into account potential sex differences. We used transgenic mice deficient p35KO and wild type (WT) control of 21-25 postnatal days. We assessed WM using the Y-maze task and neuronal activity in brain related areas using c-FOS immunostaining. Data was analyzed using ANOVA.
The p35KO mice of both sexes exhibited impaired WM compared with WT mice. Also, the performance of p35KO males treated with MTPH was similar to WT male control group, which suggests an improvement of WM induced by MTPH.
In conclusion, our study emphasizes the importance of the Cdk5/p35 complex in WM processes. Moreover, it demonstrates the potential of MTPH to rescue WM impairments caused by disrupted Cdk5 activation in males.