| Autor: |
Johnsen LØ; Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark., Sigad A; Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark., Friis KA; Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark., Berg PM; Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark., Damkier HH; Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark. |
| Jazyk: |
angličtina |
| Zdroj: |
Frontiers in physiology [Front Physiol] 2024 Oct 21; Vol. 15, pp. 1491793. Date of Electronic Publication: 2024 Oct 21 (Print Publication: 2024). |
| DOI: |
10.3389/fphys.2024.1491793 |
| Abstrakt: |
Regulation of cerebrospinal fluid (CSF) pH and brain pH are vital for all brain cells. The acute regulation of CSF pH is dependent on the transport of HCO 3 - across the choroid plexus in the brain ventricles. Acute regulation in response to acidosis is dependent on H + export and HCO 3 - import across the plasma membrane. Acute regulation in response to alkalosis is dependent on HCO 3 - export across the plasma membrane. The objective of the study was to investigate the contribution of the Na + -dependent HCO 3 - transporters, Ncbe, NBCn1, and NBCe2 to CSF pH regulation during chronic metabolic acidosis in mice. To induce metabolic acidosis, mice received 0.28 M ammonium chloride (NH 4 Cl) in the drinking water for three, five, or seven days. While in vivo, CSF pH measurements did not differ, measurements of CSF [HCO 3 - ] revealed a significantly lower CSF [HCO 3 - ] after three days of acid-loading. Immunoblotting of choroid plexus protein samples showed that the abundance of the basolateral Na + /HCO 3 - transporter, NBCn1, was significantly increased. This was followed by a significant increase in CSF secretion rate determined by ventriculo-cisternal perfusion. After five days of treatment with NH 4 Cl, CSF [HCO 3 - ] levels were normalized. After the normalization of CSF [HCO 3 - ], CSF secretion was no longer increased but the abundance of the basolateral Na + -dependent HCO 3 - transporters Ncbe and NBCn1 increased. The luminal HCO 3 - transporter, NBCe2, was unaffected by the treatment. In conclusion, we establish that 1) acidotic conditions increase the abundance of the basolateral Na + -dependent HCO 3 - transporters in the choroid plexus, 2) NH 4 Cl loading in mice lowers CSF [HCO 3 - ] and 3) leads to increased CSF secretion likely caused by the increased capacity for transepithelial transport of Na + and HCO 3 - in the choroid plexus.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Johnsen, Sigad, Friis, Berg and Damkier.) |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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