Brain Uptake of Folate Forms in the Presence of Folate Receptor Alpha Antibodies in Young Rats: Folate and Antibody Distribution.
Brain Uptake of Folate Forms in the Presence of Folate Receptor Alpha Antibodies in Young Rats: Folate and Antibody Distribution.
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DOI：
10.3390/nu15051167
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发表时间：
2023-02-25
期刊：
影响因子：
5.9
通讯作者：
Quadros EV
中科院分区：
文献类型：
--
作者：
Bobrowski-Khoury N;Sequeira JM;Quadros EV
在大鼠模型中，在妊娠期间暴露于大鼠叶酸受体α抗体(FRαAb)后，FRαAb在胎盘和胎儿中积聚，阻止叶酸向胎儿大脑的运输，并在后代中产生行为缺陷。这些缺陷可以用叶酸预防。因此，我们试图评估幼鼠的叶酸向大脑的转运，并确定FRαAb在这一过程中的作用，以更好地了解自闭症谱系障碍中与脑叶酸缺乏相关的叶酸受体自身免疫紊乱。当通过腹膜腔注射(IP)时，FRαAb定位于脉络丛和血管，包括贯穿脑实质的毛细血管。生物素标记的叶酸显示分布在大脑和小脑的白质束中。由于这些抗体可以阻止叶酸向大脑的运输，我们口服了不同的叶酸形式，以确定哪种形式的叶酸被更好地吸收和运输到大脑，并且在存在FRαAb的情况下最有效地恢复大脑的叶酸状态。叶酸的三种形式，即叶酸、D、L-叶酸和左旋叶酸，被转化为甲基叶酸，而L-甲基叶酸被吸收，所有这些都被有效地分配到大脑。然而，在存在或不存在FRαAb的情况下，左亚叶酸在大脑和小脑中的叶酸浓度显著增加。我们在大鼠模型中的结果支持左亚叶酸治疗ASD儿童CFD的试验。
In a rat model, following exposure to rat folate receptor alpha antibodies (FRαAb) during gestation, FRαAb 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 FRαAb 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), FRαAb 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 FRαAb. 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 FRαAb. Our results in the rat model support testing levofolinate to treat CFD in children with ASD.