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Modeling exposure to folate receptor antibodies during neural development to understand its clinical significance.
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Quadros, Edward
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Fall 2022
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Abstract
Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder with
defined core symptoms of impaired social communication, stereotyped or repetitive behaviors,
and cognitive deficits. These core symptoms present early in childhood, which distinguishes this
disorder from other neurological disorders that share similar characteristics. To our knowledge,
there is currently no pharmacologic treatment for the core symptoms of ASD. A possible
therapeutic strategy is supplementing folate, more specifically the reduced form, folinic acid,
during pregnancy. Folate is the umbrella term for biological forms of vitamin B9. The well
recognized role of folates as precursors of DNA synthesis, single carbon exchange reactions and
in methylation reactions is a priori evidence of its requirement for cellular replication,
metabolism, and epigenetic control of gene expression. This is especially important during the
early stages of neural development. While the role of folate in cellular metabolism has been
clearly defined, there has been no study, to our knowledge, that demonstrates the characteristics
of folate uptake and distribution during gestation and early development. This is critical to
understand because of the emerging findings that folate receptor alpha autoantibodies
(FRAuAb) are linked to disruptions of neural development leading to ASD. Our lab has shown
that a rat model of exposure to IgG antibodies specific to rat folate receptor alpha during
gestation develops a behavioral phenotype comparable to the human ASD. This phenotype
appears to be preventable with folinic acid and dexamethasone treatment. Preliminary
observations in this model also suggest that the phenotype seen in rats directly exposed to
FRAb is preserved in subsequent generations. Overall, this thesis provides new data on the
uptake and distribution of folate and folate receptor antibodies in utero (Study 1, Part 1) and in
juvenile stages of development (Study 1, Part 2) and observes an appearance of deficits to a
subsequent generation of animals previously exposed to FRAb directly (Study 2)
Citation
Bobrowski-Khoury, N. (2022) Modeling exposure to folate receptor antibodies during neural development to understand its clinical significance [Doctoral Dissertation, SUNY Downstate Health Sciences University]. SUNY Open Access Repository. https://soar.suny.edu/handle/20.500.12648/14746