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  3. Hippocampal dentate gyri proteomics reveals Wnt signaling involvement in the behavioral impairment in the THRSP-overexpressing ADHD mouse model

Hippocampal dentate gyri proteomics reveals Wnt signaling involvement in the behavioral impairment in the THRSP-overexpressing ADHD mouse model

  • Commun Biol. 2023 Jan 16;6(1):55. doi: 10.1038/s42003-022-04387-5.
Raly James Perez Custodio # 1 2 3,  Hee Jin Kim # 2,  Jiyeon Kim 4,  Darlene Mae Ortiz 2,  Mikyung Kim 2 5,  Danilo Buctot 2,  Leandro Val Sayson 2,  Hyun Jun Lee 2,  Bung-Nyun Kim 6,  Eugene C Yi 7,  Jae Hoon Cheong 8
Affiliations

Affiliations

  • 1 Department of Ergonomics, Leibniz Research Centre for Working Environment and Human Factors - IfADo, Ardeystr. 67, 44139, Dortmund, Germany.
  • 2 Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarangro, Nowon-gu, Seoul, 01795, Republic of Korea.
  • 3 Institute for New Drug Development, College of Pharmacy, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do, 54896, Republic of Korea.
  • 4 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea.
  • 5 Department of Chemistry & Life Science, Sahmyook University, 815 Hwarangro, Nowon-gu, Seoul, 01795, Republic of Korea.
  • 6 Department of Psychiatry and Behavioral Science, College of Medicine, Seoul National University, 101 Daehakro, Jongno-gu, Seoul, 03080, Republic of Korea.
  • 7 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea. euyi@snu.ac.kr.
  • 8 Institute for New Drug Development, College of Pharmacy, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do, 54896, Republic of Korea. cheongjh@jbnu.ac.kr.
  • # Contributed equally.
PMID: 36646879 DOI: 10.1038/s42003-022-04387-5
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 OE) mice with defining characteristics of ADHD-PI were utilized in proteomics. Integrated proteomics and network analysis revealed an altered protein network involved in Wnt signaling. Compared with THRSP knockout (KO) mice, THRSP OE mice showed impaired attention and memory, accompanied by dysregulated Wnt signaling affecting hippocampal dentate gyrus cell proliferation and expression of markers for neural stem cell (NSC) activity. Also, combined exposure to an enriched environment and treadmill exercise could improve behavioral deficits in THRSP OE mice and Wnt signaling and NSC activity. These findings show new markers specific to the ADHD-PI presentation, converging with the ancient and evolutionary Wnt signaling pathways crucial for cell fate determination, migration, polarity, and neural patterning during neurodevelopment. These findings from THRSP OE mice support the role of Wnt signaling in neurological disorders, particularly ADHD-PI presentation.

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