Brain Uptake of Folate Forms in the Presence of Folate Receptor Alpha Antibodies in Young Rats: Folate and Antibody Distribution

In a rat model, following exposure to rat folate receptor alpha antibodies (FR alpha Ab) during gestation, FR alpha Ab accumulates in the placenta and the fetus and blocks folate transport to the fetal brain and produces behavioral deficits in the offspring. These deficits could be prevented with folinic acid. Therefore, we sought to evaluate folate transport to the brain in young rat pups and determine what effect FR alpha Ab has on this process, to better understand the folate receptor autoimmune disorder associated with cerebral folate deficiency (CFD) in autism spectrum disorders (ASD). When injected intraperitoneally (IP), FR alpha Ab localizes to the choroid plexus and blood vessels including the capillaries throughout the brain parenchyma. Biotin-tagged folic acid shows distribution in the white matter tracts in the cerebrum and cerebellum. Since these antibodies can block folate transport to the brain, we orally administered various folate forms to identify the form that is better-absorbed and transported to the brain and is most effective in restoring cerebral folate status in the presence of FR alpha Ab. The three forms of folate, namely folic acid, D,L-folinic acid and levofolinate, are converted to methylfolate while L-methylfolate is absorbed as such and all are efficiently distributed to the brain. However, significantly higher folate concentration is seen in the cerebrum and cerebellum with levofolinate in the presence or absence of FR alpha Ab. Our results in the rat model support testing levofolinate to treat CFD in children with ASD.

Automated summary

In a rat model, exposure to rat folate receptor alpha antibodies during gestation leads to the accumulation of FR alpha Ab in the placenta and fetus, blocking folate transport to the fetal brain and causing behavioral deficits in the offspring. Administering folinic acid can prevent these deficits. This study aimed to investigate the effects of FR alpha Ab on folate transport in the brain of young rat pups to gain insight into the autoimmune disorder associated with cerebral folate deficiency in autism spectrum disorders.