2023
DOI: 10.1038/s42003-022-04387-5
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Hippocampal dentate gyri proteomics reveals Wnt signaling involvement in the behavioral impairment in the THRSP-overexpressing ADHD mouse model

Abstract: Children with attention-deficit/hyperactivity disorder (ADHD) often struggle with impaired executive function, temporal processing, and visuospatial memory, hallmarks of the predominantly inattentive presentation (ADHD-PI), subserved by the hippocampus. However, the specific genes/proteins involved and how they shape hippocampal structures to influence ADHD behavior remain poorly understood. As an exploratory tool, hippocampal dentate gyri tissues from thyroid hormone-responsive protein overexpressing (THRSP O… Show more

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Cited by 9 publications
(6 citation statements)
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References 69 publications
(95 reference statements)
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“…Y-maze test (YMT): Cognition of the mice was evaluated through spatial learning and memory. Each mouse was placed in one of the Y-maze (45 × 10 × 20 cm) arms and allowed to explore freely for 10 min based on a previous study [ 31 ]. The study defines an “arm entry” as the entry of all four paws (mice) into an arm and the “alternation behavior” (actual alternations) as a consecutive entry into three arms.…”
Section: Methodsmentioning
confidence: 99%
“…Y-maze test (YMT): Cognition of the mice was evaluated through spatial learning and memory. Each mouse was placed in one of the Y-maze (45 × 10 × 20 cm) arms and allowed to explore freely for 10 min based on a previous study [ 31 ]. The study defines an “arm entry” as the entry of all four paws (mice) into an arm and the “alternation behavior” (actual alternations) as a consecutive entry into three arms.…”
Section: Methodsmentioning
confidence: 99%
“…Dysregulation in the canonical Wnt signaling pathway in ADHD and its alteration after MPH therapy was confirmed by various researchers as reviewed elsewhere ( Yde Ohki et al, 2020 ). In a mouse model overexpressing the thyroid hormone-responsive protein with defining characteristics of ADHD, a proteomic analysis of the hippocampus found an altered network of proteins involved in Wnt signaling; catenin β1 was found to be upregulated, and hippocampal gene expression of Wnt ligands, inhibitors, receptors, and co-receptors: i.e., significant reductions of the Wnt7a gene, as well as upregulation of Wnt inhibitors Dkk4 and Igfbp5 and enhanced Lrp6 expression was found ( Custodio et al, 2023 ). In humans, a significant association was found between sex-specific genetic variations of LRP5 or LRP6 co-receptors and child and adolescent ADHD ( Grünblatt et al, 2019 ).…”
Section: Wnt/mtor Pathways Evidence In Alzheimer’s Disease and Attent...mentioning
confidence: 99%
“…Results converge with the evolutionary Wnt signaling pathways crucial for neurodevelopment, supporting the role of Wnt signaling in ADHD, specifically ADHD-PI presentation. 210 Second, it remains unclear how THRSP modulates the dopamine-related genes altered in THRSP OE mice. THRSP is a thyroid-hormone-related protein.…”
Section: Directionsmentioning
confidence: 99%
“…Notably, our preliminary findings indicate that altered dopamine-related genes and thyroid hormones (T3) may be responsible for this behavior, given that the dopaminergic system and thyroid hormones are directly involved in regulating attention and cognitive behaviors. , Also, recently, our new study provided significant findings through identification of hippocampal dentate gyri (DG) molecular signatures in THRSP OE mice rather than typical “culprits,” such as those identified (dopaminergic and thyroid system hypothesis). Results converge with the evolutionary Wnt signaling pathways crucial for neurodevelopment, supporting the role of Wnt signaling in ADHD, specifically ADHD-PI presentation . Second, it remains unclear how THRSP modulates the dopamine-related genes altered in THRSP OE mice.…”
Section: Conclusion Challenges and Future Directionsmentioning
confidence: 99%