한빛사논문
- 조회736
Gaeun Park1,2,15, Wooyoung Eric Jang3,15, Seoyeon Kim4,5,15, Edson Luck Gonzales6, Jungeun Ji4,5, Seunghwan Choi7, Yujin Kim4,5, Ji Hwan Park8, Hazara Begum Mohammad8, Geul Bang9, Minkyung Kang1,2, Soobin Kim1,2, Se Jin Jeon6, Jin Young Kim9, Kwang Pyo Kim3,10, Chan Young Shin6,*, Joon-Yong An4,5,7,*, Min-Sik Kim8,11,12,* and Yong-Seok Lee1,2,13,14,*
1Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
2Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
3Department of Applied Chemistry, Institute of Natural Science, Global Center for Pharmaceutical Ingredient Materials, Kyung Hee University, Yongin 17104, Republic of Korea.
4Department of Integrated Biomedical and Life Science, Korea University, Seoul 02841, Republic of Korea.
5BK21FOUR R&E Center for Learning Health Systems, Korea University, Seoul 02841, Republic of Korea.
6School of Medicine and Center for Neuroscience Research, Konkuk University, Seoul 05029, Republic of Korea.
7School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 02841, Republic of Korea.
8Department of New Biology, DGIST, Daegu 42988, Republic of Korea.
9Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Ochang 28119, Republic of Korea.
10Department of Biomedical Science and Technology, Kyung Hee Medical Science Research Institute, Kyung Hee University, Seoul 02447, Republic of Korea.
11New Biology Research Center, DGIST, Daegu 42988, Republic of Korea.
12Center for Cell Fate Reprogramming and Control, DGIST, Daegu 42988, Republic of Korea.
13Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
14Wide River Institute of Immunology, Seoul National University, Hongcheon 25159, Republic of Korea.
15These authors contributed equally: Gaeun Park, Wooyoung Eric Jang, Seoyeon Kim.
*Corresponding author: correspondence to Chan Young Shin, Joon-Yong An, Min-Sik Kim or Yong-Seok Lee
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social behavior and communication, repetitive behaviors, and restricted interests. In addition to genetic factors, environmental factors such as prenatal drug exposure contribute to the development of ASD. However, how those prenatal factors induce behavioral deficits in the adult stage is not clear. To elucidate ASD pathogenesis at the molecular level, we performed a high-resolution mass spectrometry-based quantitative proteomic analysis on the prefrontal cortex (PFC) of mice exposed to valproic acid (VPA) in utero, a widely used animal model of ASD. Differentially expressed proteins (DEPs) in VPA-exposed mice showed significant overlap with ASD risk genes, including differentially expressed genes from the postmortem cortex of ASD patients. Functional annotations of the DEPs revealed significant enrichment in the Wnt/β-catenin signaling pathway, which is dysregulated by the upregulation of Rnf146 in VPA-exposed mice. Consistently, overexpressing Rnf146 in the PFC impaired social behaviors and altered the Wnt signaling pathway in adult mice. Furthermore, Rnf146-overexpressing PFC neurons showed increased excitatory synaptic transmission, which may underlie impaired social behavior. These results demonstrate that Rnf146 is critical for social behavior and that dysregulation of Rnf146 underlies social deficits in VPA-exposed mice.
논문정보
- Research article
- 2023년 08월 (BRIC 등록일 2023-08-02)
- 국내 연구진
- 생명과학 > 신경생물학
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