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Aberrant brain functional and structural developments in MECP2 duplication rats
Xu, Ming1,2; Qi, Shile3; Calhoun, Vince4; Dai, Jiankun5,8; Yu, Bin5,9; Zhang, Kaiwei5; Pei, Mengchao5; Li, Chenjian6,7; Wei, Yusheng6,7; Jiang, Rongtao1; Zhi, Dongmei1,2; Huang, Zhimin6,7; Qiu, Zilong5; Liang, Zhifeng5; Sui, Jing10
Source PublicationNeurobiology of Disease

Transgenic animal models with homologous etiology provide a promising way to pursue the neurobiological substrates of the behavioral deficits in autism spectrum disorder (ASD). Gain-of-function mutations of MECP2 cause MECP2 duplication syndrome, a severe neurological disorder with core symptoms of ASD. However, abnormal brain developments underlying the autistic-like behavioral deficits of MECP2 duplication syndrome are rarely investigated. To this end, a human MECP2 duplication (MECP2-DP) rat model was created by the bacterial artificial chromosome transgenic method. Functional and structural magnetic resonance imaging (MRI) with high-field were performed on 16 male MECP2-DP rats and 15 male wildtype rats at postnatal 28 days, 42 days, and 56 days old. Multimodal fusion analyses guided by locomotor-relevant metrics and social novelty time separately were applied to identify abnormal brain networks associated with diverse behavioral deficits induced by MECP2 duplication. Aberrant functional developments of a core network primarily composed of the dorsal medial prefrontal cortex (dmPFC) and retrosplenial cortex (RSP) were detected to associate with diverse behavioral phenotypes in MECP2-DP rats. Altered developments of gray matter volume were detected in the hippocampus and thalamus. We conclude that gain-of-function mutations of MECP2 induce aberrant functional activities in the default-mode-like network and aberrant volumetric changes in the brain, resulting in autistic-like behavioral deficits. Our results gain critical insights into the biomarker of MECP2 duplication syndrome and the neurobiological underpinnings of the behavioral deficits in ASD. 

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Document Type期刊论文
Corresponding AuthorLiang, Zhifeng; Sui, Jing
Affiliation1.Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences; Beijing, 100190, China
2.School of Artificial Intelligence, University of Chinese Academy of Sciences; Beijing, 100190, China
3.College of Computer Science and Technology, Nanjing University of Aeronautics and Astronautics; Nanjing, 211106, China
4.Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia Institute of Technology, Georgia State University, Emory University; Atlanta, GA 30303, USA
5.Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, CAS Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences; Shanghai, 200031, China
6.Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Peking University School of Life Sciences; Beijing, 100871, China
7.PKU-IDG/McGovern Institute for Brain Research, Peking-Tsinghua Center for Life Sciences; Beijing, 100871, China
8.Present address: Bruker BioSpin PCI; Shanghai, China
9.Present address: Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, NHC and CAMS Key Laboratory of Medical Neurobiology, MDP Frontier Science Center for Brain Research and Brain-Machine Integration, Zhejiang University School of Brain Science and Brain Medicine; Hangzhou, 310058, China
10.IDG/McGovern Institute for Brain Research, State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, 100875, China
First Author AffilicationChinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing 100190, Peoples R China
Recommended Citation
GB/T 7714
Xu, Ming,Qi, Shile,Calhoun, Vince,et al. Aberrant brain functional and structural developments in MECP2 duplication rats[J]. Neurobiology of Disease,2022,173:105838.
APA Xu, Ming.,Qi, Shile.,Calhoun, Vince.,Dai, Jiankun.,Yu, Bin.,...&Sui, Jing.(2022).Aberrant brain functional and structural developments in MECP2 duplication rats.Neurobiology of Disease,173,105838.
MLA Xu, Ming,et al."Aberrant brain functional and structural developments in MECP2 duplication rats".Neurobiology of Disease 173(2022):105838.
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