12 Nov Mechanism Identified Linking ASD and Intellectual Disability, Opening Door To Development of Treatment Options
MedicalResearch.com Interview with:
Woo-Yang Kim, Ph.D
Department of Developmental Neuroscience
University of Nebraska Medical Center
Omaha, NE 68198-5960
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Autism impairs the ability of individuals to communicate and interact with others. About 75 percent of individuals with autism also have intellectual disability, which is characterized by significant limitations in cognitive functions and adaptive behaviors. While autism and intellectual disability are currently defined using behavioral criteria, little is known about the neuropathogenesis of these conditions.
Recent genetic studies have reported that haploinsufficiency of ARID1B causes autism and intellectual disability. However, the neurobiological function of ARID1B during brain development is unknown.
Our study investigated the neurobiological role of the gene in brain development. Using genetically-modified mice, we found that Arid1b haploinsufficiency leads to an excitation-inhibition imbalance by reducing the number of GABAergic interneurons in the cerebral cortex. Furthermore, we showed that treatment with a GABAA-receptor positive allosteric modulator rescues ASD-like behavior and cognitive dysfunction in Arid1b-haploinsufficient mice, suggesting an association between lower numbers of GABAergic interneurons and behavioral outcomes.
Our findings suggest a pathogenic mechanism for Autism Spectrum Disorder and intellectual disability.
MedicalResearch.com: What should clinicians and patients take away from your report?
Response: There are no drugs or genetic treatments to prevent Autism Spectrum Disorder or intellectual disability. The only treatment options focus on behavioral management and educational and physical therapies.
Development of therapeutic tools requires identification and targeting of causative factors. Important messages of our study include:
1) Identification of cellular and molecular basis for ARID1B haploinsufficiency-related neurodevelopmental disorders;
2) Creation of an animal model for autism and intellectual disability;
3) Pharmacological manipulation of GABA signaling as a potential treatment strategy for cognitive and social dysfunctions in autism- or intellectual disability-associated disorders.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Our study created a designer mouse that can be used for future studies for autism and intellectual disability. Brain and neural circuit development in this mouse model remains to be elucidated. Particularly, future research may further define specific mechanisms for autism and intellectual disability and identify which of the many GABA neurons are specifically involved.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
- Eui-Man Jung, Jeffrey Jay Moffat, Jinxu Liu, Shashank Manohar Dravid, Channabasavaiah Basavaraju Gurumurthy, Woo-Yang Kim. Arid1b haploinsufficiency disrupts cortical interneuron development and mouse behavior. Nature Neuroscience, 2017; DOI: 1038/s41593-017-0013-0
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