Summary
This study reveals that drug transport across the blood-cerebrospinal fluid barrier is governed by circadian rhythms and sex hormones, with transporters such as Oat3 and Abcc4 showing time-of-day-dependent expression. For healthcare and pharmaceutical applications, these findings suggest that drug dosing schedules—particularly for agents like methotrexate—may need to account for time of day and hormonal status to optimize efficacy and minimize toxicity.
Key Findings
- Circadian expression of Abcc1 and Oat3 was found in female rats, while Abcg4 showed circadian expression in male rats, indicating sex-specific differences in transporter rhythmicity.
- Oat3 circadian expression in female rats was dependent on ovarian hormones, as confirmed by comparison between sham-operated and ovariectomized rats.
- Methotrexate (MTX) transport across the human blood-cerebrospinal fluid barrier in vitro exhibited a circadian pattern, with Abcc4 identified as partially responsible for this rhythmic transport across the basal membrane of choroid plexus epithelial cells.
Categories
Sleep & Circadian Health: Demonstrates circadian rhythmicity in choroid plexus transporter expression, with sex-hormone-dependent oscillations in Oat3, Abcc1, and Abcg4.
The Science of Light: Provides mechanistic insight into peripheral circadian oscillators (choroid plexus) and how sex hormones modulate molecular clock outputs in non-SCN tissues.
Author(s)
RM Mineiro
Publication Year
2020
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