Embryonic stem cell transplants as a therapeutic strategy in a rodent model of autism

Autism is a neurodevelopmental disorder characterized by disruptions in three core behavioral domains: deficits in social interaction, impairments in communication, and repetitive and stereotyped patterns of behavior or thought. There are currently no drugs available for the treatment of the core sy...

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Bibliographic Details
Published in:Neuropsychopharmacology (New York, N.Y.) N.Y.), 2018-07, Vol.43 (8), p.1789-1798
Main Authors: Donegan, Jennifer J, Boley, Angela M, Lodge, Daniel J
Format: Article
Language:English
Subjects:
Action Potentials - physiology
Animals
Attention
Autism
Autistic Disorder - pathology
Autistic Disorder - physiopathology
Autistic Disorder - therapy
Cell Line
Cognitive ability
Disease Models, Animal
Embryonic Stem Cells - pathology
Embryonic Stem Cells - physiology
Embryonic Stem Cells - transplantation
Executive Function
Interneurons
Interneurons - pathology
Interneurons - physiology
Interneurons - transplantation
Male
Mice
Nervous system
Neurodevelopmental disorders
Neurosciences
Parvalbumin
Poly I-C
Polyinosinic:polycytidylic acid
Prefrontal cortex
Prefrontal Cortex - pathology
Prefrontal Cortex - physiopathology
Prepulse Inhibition
Pyramidal Cells - pathology
Pyramidal Cells - physiology
Rats, Sprague-Dawley
Side effects
Social Behavior
Social interaction
Stem cells
Stereotyped behavior
Transplants
Vocalization, Animal
γ-Aminobutyric acid
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Summary:Autism is a neurodevelopmental disorder characterized by disruptions in three core behavioral domains: deficits in social interaction, impairments in communication, and repetitive and stereotyped patterns of behavior or thought. There are currently no drugs available for the treatment of the core symptoms of ASD and drugs that target comorbid symptoms often have serious adverse side effects, suggesting an urgent need for new therapeutic strategies. The neurobiology of autism is complex, but converging evidence suggests that ASD involves disruptions in the inhibitory GABAergic neurotransmitter system. Specifically, people with autism have a reduction in parvalbumin (PV)-containing interneurons in the PFC, leading to the suggestion that restoring interneuron function in this region may be a novel therapeutic approach for ASD. Here we used a dual-reporter embryonic stem cell line to generate enriched populations of PV-positive interneurons, which were transplanted into the medial prefrontal cortex (mPFC) of the Poly I:C rodent model of autism. PV interneuron transplants were able to decrease pyramidal cell firing in the mPFC and alleviated deficits in social interaction and cognitive flexibility. Our results suggest that restoring PV interneuron function in the mPFC may be a novel and effective treatment strategy to reduce the core symptoms of autism.
ISSN:0893-133X
1740-634X
DOI:10.1038/s41386-018-0021-0