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Prevention of behavioral deficits in rats exposed to folate receptor antibodies: implication in autism
A Desai1, J M Sequeira2, E V Quadros2
1School of Graduate Studies, State University New York-Downstate Medical Center, Brooklyn, NY, USA.
Insights
Folate receptor alpha autoantibodies in pregnant rats caused developmental deficits in offspring, which were prevented by folinic acid. This suggests a potential cause for autism spectrum disorder (ASD) and other developmental disorders in humans.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Folate receptor alpha (FRα) autoantibodies are linked to fetal abnormalities and developmental disorders.
- Over 70% of children with autism spectrum disorder (ASD) test positive for FRα autoantibodies.
- High-dose folinic acid has shown benefits in treating children with ASD and FRα autoantibodies.
Purpose of the Study:
- To investigate the impact of FRα autoantibodies on fetal development and offspring neurodevelopment in a rat model.
- To determine if folinic acid or dexamethasone can prevent FRα autoantibody-induced developmental deficits.
Main Methods:
- Administration of antibodies to rat FRα during gestation in a rat model.
- Assessment of communication, learning, and cognitive deficits in offspring.
- Evaluation of the preventative effects of folinic acid and dexamethasone.
Main Results:
- Antibodies to rat FRα administered during gestation induced communication, learning, and cognitive deficits in offspring.
- Folinic acid and dexamethasone prevented these deficits.
- FRα autoantibodies were shown to trigger inflammation and block folate transport to the developing brain.
Conclusions:
- FRα autoantibodies during fetal development may contribute to brain dysfunction, including ASD and other developmental disorders.
- Identifying and treating women with FRα autoantibodies during pregnancy with high-dose folinic acid may reduce the risk of developmental deficits in offspring.
Abstract:
Folate receptor alpha (FRα) autoantibodies have been associated with fetal abnormalities and cerebral folate deficiency-related developmental disorders. Over 70% of the children with autism spectrum disorders (ASD) are positive for these autoantibodies and high-dose folinic acid is beneficial in treating these children. Here we show that antibodies (Abs) to the rat FRα administered during gestation produce communication, learning and cognitive deficits in a rat model that can be prevented by folinic acid and dexamethasone. FRα Ab can trigger inflammation as well as block folate transport to the fetus and to the developing brain to produce the functional deficits. In humans, exposure to FRα autoantibodies during fetal development and infancy could contribute to brain dysfunction such as that seen in ASD and other developmental disorders. Identifying women positive for the autoantibody and treating them with high-dose folinic acid along with other interventions to lower the autoantibody titer are effective strategies that may be considered to reduce the risk of having a child with developmental deficits.
