Published in Molecular Psychiatry, a team of scientists from the University of Minnesota Medical School, University of Texas Health San Antonio, and the Biomedical Research Institute (BRI) of the Foundation for Research and Technology Hellas (FORTH) in Greece found that the disruption of a circadian clock gene may be involved in the development of autism spectrum disorder.
Autism spectrum disorder, or ASD, refers to a neurodevelopmental disorder characterized by a wide range of behavioral conditions including challenges with social skills, repetitive behaviors, speech and nonverbal communication. According to the Centers for Disease Control and Prevention, ASD affects one in 44 children in the U.S.
About 50-80% of children with ASD have sleep problems, compared to less than 30% in the general population. The causes of sleep problems in ASD are not entirely clear, but a malfunctioning body clock could be the culprit.
It has long been recognized that the function of the body clock is frequently disrupted in autism patients and these patients often exhibit various sleep problems, said Ruifeng Cao, MD, PhD, an assistant professor of neuroscience at the U of M Medical School, Duluth Campus and co-author of the study. But, it is not known whether clock gene disruption can directly cause autism.
The study found that the disruption of an essential clock gene in preclinical models can lead to autistic-like phenotypes. Specifically, the global or cerebellar deletion of the Bmal1 gene can cause severe impairments in sociability, social communication and excessive repetitive behaviors.
The models also illustrated damages to their cerebellum or cerebellar ataxia. The research team further studied the pathological changes in the cerebellum and found a number of cellular and molecular changes that indicate neurodevelopmental deficits.
Clock gene disruption could be a mechanism underlying several forms of autism and potentially other neurodevelopmental conditions, and this finding paves the way for further exciting research, said Christos Gkogkas, PhD, a lab principal investigator in neurobiology at BRI of FORTH.
The research team plans to continue to study other clock genes that are found mutated in ASD. More importantly, they recommend development of novel therapeutic strategies based on their findings.
The study is supported by grants from the National Institute of Health and the Winston and Maxine Wallin Neuroscience Discovery Fund.
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The research team consists of Drs. Harry Orr, Alfonso Araque, Paulo Kofuji, and Jonathan Gewirtz (now at Arizona State University) from the U of M Medical School; Dr. Victor Jin from UT Health San Antonio; and Dr. Christos Gkogkas from BRI-FORTH in Greece.
About the University of Minnesota Medical SchoolThe University of Minnesota Medical School is at the forefront of learning and discovery, transforming medical care and educating the next generation of physicians. Our graduates and faculty produce high-impact biomedical research and advance the practice of medicine. We acknowledge that the U of M Medical School, both the Twin Cities campus and Duluth campus, is located on traditional, ancestral and contemporary lands of the Dakota and the Ojibwe, and scores of other Indigenous people, and we affirm our commitment to tribal communities and their sovereignty as we seek to improve and strengthen our relations with tribal nations. For more information about the U of M Medical School, please visit med.umn.edu.
The Biomedical Research Institute of FORTHThe Biomedical Research Institute (BRI) of FORTH at Ioannina consists of 18 research teams that comprise 140 members. The groups of BRI work in basic molecular and cellular biology areas of biomedical research with high interest in public health and biomedicine, such as vascular biology, stem cell biology and regenerative medicine, cancer biology, neurobiology, and biomedical technology.
The Foundation for Research and Technology - Hellas (FORTH) is one of the largest research centers in Greece, comprising nine Research Institutes. FORTH conducts specialized scientific research in strategic high-added value sectors, focusing on interdisciplinary research and development (R&D) activities in areas of major scientific, societal and economic interest.
Molecular Psychiatry
Observational study
Animals
Autistic-like behavior and cerebellar dysfunction in Bmal1 mutant mice ameliorated by mTORC1 inhibition
17-Mar-2022
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Research Brief: Clock gene mutation found to contribute to the development of autism - EurekAlert
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