Proteomics data reveals Wnt signaling involvement in the hippocampal-dependent behavioral impairment in THRSP-overexpressing ADHD mouse model

ABSTRACT: Despite the predominance and high heritability of Attention-Deficit/Hyperactivity Disorder (ADHD), its etiology remains elusive. Preclinical and clinical evidence partly points to impaired limbic system function, particularly that of the hippocampus (HPC). Children diagnosed with ADHD often struggle with deficits in executive function, temporal processing, and visuospatial memory, the defining hallmarks of the predominantly inattentive presentation (ADHD-PI), thought to be subserved by the HPC brain region. However, the specific genes/proteins involved and how they shape the hippocampal makeup to influence ADHD behavior are poorly understood. As an exploratory tool, hippocampal tissues from a mouse model overexpressing thyroid hormone-responsive protein (THRSP), with defining characteristics of ADHD-PI presentation, were utilized for proteomic analyses. Results revealed differential expressions of proteins involved in Wnt signaling. Compared to THRSP knockout (KO), THRSP OE mice have impaired attention and memory concomitant to dysregulated Wnt signaling affecting hippocampal cell proliferation (BrdU) and neurogenic markers expressions (i.e., NEU-N, GFAP), markers of neural stem cell (NSC) activity. Also, exposure to a combination of enriched environment and treadmill exercise improves behavioral deficits in THRSP OE mice and improves Wnt signaling and NSC activity.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Jiyeon Kim  

LAB HEAD: Eugene C. Yi

PROVIDER: PXD038525 | Pride | 2023-01-18

REPOSITORIES: Pride