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ORIGINAL RESEARCH article

Front. Psychiatry
Sec. Autism
Volume 15 - 2024 | doi: 10.3389/fpsyt.2024.1396716
This article is part of the Research Topic Effects of Autism Spectrum Disorder (ASD) Risk Genes on Phenotypes of Each Hierarchy View all 4 articles

Deficiency of Autism Susceptibility Gene Trio in Cerebellar Purkinje Cells Leads to delayed Motor Impairments

Provisionally accepted
Jinxin Wang Jinxin Wang 1,2Yimeng Li Yimeng Li 2Dai Zhang Dai Zhang 3Jun Li Jun Li 3*
  • 1 IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, Beijing, China
  • 2 Chinese Institute for Brain Research, Beijing (CIBR), Beijing, Beijing Municipality, China
  • 3 Peking University Sixth Hospital, Beijing, Beijing Municipality, China

The final, formatted version of the article will be published soon.

    Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by social interaction deficits, restricted interests and repetitive behaviors. The co-occurrence of motor impairments exacerbates the severity and societal impact of ASD, but the underlying mechanism remains to be elucidated. Research on the comorbidities of ASD including motor impairments could benefit in the life quality improvement in patients with ASD. Here we aimed at investigating the motor behaviors in mice with Trio deletion in Purkinje cells (PCs), and further exploring the cellular and molecular mechanisms. The protein level of Calbindin as PCs' marker was determined. Behaviors including spontaneous locomotion activity, rotarod, beam balance and gait were tested in mice with the ages of 12-week and 20-week. Magnetic resonance imaging (MRI) scanning with T2 and DTI sequencing was performed in 12-week old mice. Although Trio fl/fl; Pcp2-Cre mice showed significant impairments of spontaneous locomotion activity in both 12-week and 20-week ages, only the 20-week but not 12-week Trio fl/fl; Pcp2-Cre mice showed extra mild abnormal motor, fine motor coordination, and gait. The decreased expression of Calbindin existed in both 12-week and 20-week old mice compared with control. Differentially expressed genes analysis from RNA-Seq and Gene Co-expression Network Analysis (GCNA) showed that Syne1 and its co-expressed genes were upregulated in Trio fl/fl; Pcp2-Cre mice compared to controls. In addition, abnormal ADC values suggested the long-term chronic damage in the cerebellum. Together, our findings indicate that the motor dysfunction in ASD are affected by Trio deletion in PCs with delayed in onset, accompanied with alterations in MRI, histological, and epigenetic level.

    Keywords: Autism Spectrum Disorder, TRIO, Motor Dysfunctions, Cerebellum, Purkinje Cells

    Received: 06 Mar 2024; Accepted: 02 Sep 2024.

    Copyright: © 2024 Wang, Li, Zhang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jun Li, Peking University Sixth Hospital, Beijing, 100191, Beijing Municipality, China

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