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 (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....
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/5/1167 |
| _version_ | 1797614651447443456 |
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| author | Natasha Bobrowski-Khoury Jeffrey M. Sequeira Edward V. Quadros |
| author_facet | Natasha Bobrowski-Khoury Jeffrey M. Sequeira Edward V. Quadros |
| author_sort | Natasha Bobrowski-Khoury |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T07:14:24Z |
| format | Article |
| id | doaj.art-389b0781c82e4eb38bce69109c390352 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-11T07:14:24Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-389b0781c82e4eb38bce69109c3903522023-11-17T08:20:32ZengMDPI AGNutrients2072-66432023-02-01155116710.3390/nu15051167Brain Uptake of Folate Forms in the Presence of Folate Receptor Alpha Antibodies in Young Rats: Folate and Antibody DistributionNatasha Bobrowski-Khoury0Jeffrey M. Sequeira1Edward V. Quadros2School of Graduate Studies, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, USADepartment of Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, USADepartment of Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, USAIn 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.https://www.mdpi.com/2072-6643/15/5/1167folatefolate receptor alphalevofolinatebrain uptakeautismcerebral folate deficiency |
| spellingShingle | Natasha Bobrowski-Khoury Jeffrey M. Sequeira Edward V. Quadros Brain Uptake of Folate Forms in the Presence of Folate Receptor Alpha Antibodies in Young Rats: Folate and Antibody Distribution Nutrients folate folate receptor alpha levofolinate brain uptake autism cerebral folate deficiency |
| title | Brain Uptake of Folate Forms in the Presence of Folate Receptor Alpha Antibodies in Young Rats: Folate and Antibody Distribution |
| title_full | Brain Uptake of Folate Forms in the Presence of Folate Receptor Alpha Antibodies in Young Rats: Folate and Antibody Distribution |
| title_fullStr | Brain Uptake of Folate Forms in the Presence of Folate Receptor Alpha Antibodies in Young Rats: Folate and Antibody Distribution |
| title_full_unstemmed | Brain Uptake of Folate Forms in the Presence of Folate Receptor Alpha Antibodies in Young Rats: Folate and Antibody Distribution |
| title_short | Brain Uptake of Folate Forms in the Presence of Folate Receptor Alpha Antibodies in Young Rats: Folate and Antibody Distribution |
| title_sort | brain uptake of folate forms in the presence of folate receptor alpha antibodies in young rats folate and antibody distribution |
| topic | folate folate receptor alpha levofolinate brain uptake autism cerebral folate deficiency |
| url | https://www.mdpi.com/2072-6643/15/5/1167 |
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