Danielle S. LeServe
Research Technician II
Danielle S. LeServe, Marilia Garcia De Oliveira, Maria Julia Dalton, Felipe Rong, Gabriela Ribeiro, Gabriel Pasquarelli Do Nascimento, Rafael M. Rezende
Rafael M. Rezende
Research Category: Neurosciences
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by a range of symptoms, including deficits in social skills and communication and repetitive behaviors. Previous research has shown that the maternal immune activation (MIA) model produces a predictive mouse model for autism. In this model, pregnant mice are injected with viral mimic polyinosinic: polycytidylic acid (poly (I:C)) on gestational day 12.5. Pups whose mothers were injected with poly (I: C) show classic symptoms of autism, including repetitive behavior and impaired social interaction with a novel mouse. We found that offspring from poly (I:C)-treated dams showed a distinct fecal micro-RNA (miRNA) signature compared to offspring from PBS-injected dams. Fecal miRNAs are small non-coding RNA fragments that we have found to regulate gene expression in microbes, favoring or inhibiting their growth. We isolated three specific poly (I:C)) deficient miRNAs through extractions and gave the miRNAs back to offspring from poly (I:C)- and PBS-treated dams through oral gavage. We found that oral administration of a combination of these three miRNAs abolished the repetitive behavior and improved social interaction with a novel mouse, suggesting that orally administered fecal miRNAs may constitute a novel and promising therapeutic strategy to treat behavioral abnormalities associated with ASD.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with various symptoms, including poor social skills, communication, and repetitive behaviors. Past research has shown that maternal immune activation with an injection of a viral mimic named polyinosinic-polycytidylic acid (poly (I:C)) leads to ASD-like symptoms in the offspring, including repetitive behavior and impaired social interactions with novel mice. These offspring also display differences in fecal micro-RNAs (miRNAs), which are small fragments of RNA that are not involved in protein synthesis. Fecal miRNAs are produced by intestinal cells and play an essential role in modulating the microbiome, which is a collection of different microbes (bacteria, fungi, and viruses) and their metabolic products found in the gut. Fecal miRNAs can change the makeup of the microbiome by favoring or inhibiting certain microbes. We found three specific miRNAs that were reduced in the feces of offspring from poly (I:C) treated mothers. We then investigated whether giving these three miRNAs back to offspring by oral administration would alleviate their symptoms. We found that orally administered fecal miRNAs improved their social interaction with a novel mouse and abolished their repetitive behavior. These findings suggest fecal miRNAs may be a promising therapy to treat behavioral symptoms of ASD.