Ms. Natasha Bobrowski-Khoury, in the laboratory of Dr. EdQuadros and the program of Neural & Behavioral Science will defend herthesis:

Modeling exposure to folate receptor alpha antibody during neuraldevelopment to understand its clinical significance. 

on Friday, December 9^that 2pm, in EB Lecture Hall 1A and via Zoom

Autism spectrum disorder (ASD) is a multifactorialneurodevelopmental disorder with defined core symptoms of impaired socialcommunication, stereotyped or repetitive behaviors, and cognitive deficits.These core symptoms present early in childhood, which distinguishes thisdisorder from other neurological disorders that share similar characteristics.To our knowledge, there is currently no pharmacologic treatment for the coresymptoms of ASD. A possible therapeutic strategy is supplementing folate, morespecifically the reduced form, folinic acid, during pregnancy. Folate is theumbrella term for biological forms of vitamin B9. The well recognized role offolates as precursors of DNA synthesis, single carbon exchange reactions and inmethylation reactions is a priori evidence of its requirement forcellular 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, therehas been no study, to our knowledge, that demonstrates the characteristics offolate uptake and distribution during gestation and early development.  This is critical to understand because of theemerging findings that folate receptor alpha autoantibodies (FRaAuAb)are linked to disruptions of neural development leading to ASD. Our lab hasshown that a rat model of exposure to IgG antibodies specific to rat folatereceptor alpha during gestation develops a behavioral phenotype comparable tothe human ASD. This phenotype appears to be preventable with folinic acid anddexamethasone treatment. Preliminary observations in this model also suggestthat the phenotype seen in rats directly exposed to FRAb is preserved insubsequent generations. Overall, this thesis provides new data on the uptakeand distribution of folate and folate receptor antibodies in utero (Study1, Part 1) and in juvenile stages of development (Study 1, Part 2) andobserves an appearance of deficits to a subsequent generation of animalspreviously exposed to FRAb directly (Study 2).  

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