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Prevention of behavioral deficits in rats exposed to folate receptor antibodies: implication in autism

Molecular Psychiatry volume 22, pages 1291–1297 (2017)Cite this article

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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.

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Acknowledgements

Funding for this work was provided by Autism Speaks grant no. 8202.

Author contributions

AD, JMS and EVQ designed the studies. AD and JMS conducted all experiments. AD, JMS and EVQ participated in the writing of the manuscript.

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Authors and Affiliations

  1. School of Graduate Studies, State University New York-Downstate Medical Center, Brooklyn, NY, USA

    A Desai

  2. Department of Medicine, State University New York-Downstate Medical Center, Brooklyn, NY, USA

    J M Sequeira & E V Quadros

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  1. A Desai
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Corresponding author

Correspondence to E V Quadros.

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Competing interests

Two of the authors (JMS and EVQ) are inventors on a US patent for the detection of FRalpha autoantibodies issued to the Research Foundation of the State University of New York, USA. The other author declares no conflict of interest.

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Desai, A., Sequeira, J. & Quadros, E. Prevention of behavioral deficits in rats exposed to folate receptor antibodies: implication in autism. Mol Psychiatry 22, 1291–1297 (2017). https://doi.org/10.1038/mp.2016.153

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