AUTHOR=Johnsen Laura Øllegaard , Sigad Ahmed , Friis Kathrine Abildskov , Berg Peder Matzen , Damkier Helle Hasager 

TITLE=NH4Cl-induced metabolic acidosis increases the abundance of HCO3− transporters in the choroid plexus of mice

JOURNAL=Frontiers in Physiology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2024.1491793

DOI=10.3389/fphys.2024.1491793

ISSN=1664-042X

ABSTRACT=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 HCO3 -across the choroid plexus in the brain ventricles. Acute regulation in response to acidosis is dependent on H + export and HCO3 -import across the plasma membrane. Acute regulation in response to alkalosis is dependent on HCO3 -export across the plasma membrane. The objective of the study was to investigate the contribution of the Na +dependent HCO3 -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 (NH4Cl) in the drinking water for three, five, or seven days. While in vivo, CSF pH measurements did not differ, measurements of CSF [HCO3 -] revealed a significantly lower CSF [HCO3 -] after three days of acid-loading. Immunoblotting of choroid plexus protein samples showed that the abundance of the basolateral Na + / HCO3 -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 NH4Cl, CSF [HCO3 -] levels were normalized. After the normalization of CSF [HCO3 - ], CSF secretion was no longer increased but the abundance of the basolateral Na + -dependent HCO3 - transporters Ncbe and NBCn1 increased. The luminal HCO3 -transporter, NBCe2, was unaffected by the treatment.In conclusion, we establish that 1) acidotic conditions increase the abundance of the basolateral Na +dependent HCO3 -transporters in the choroid plexus, 2) NH4Cl loading in mice lowers CSF [HCO3 -], and 3) leads to increased CSF secretion likely caused by the increased capacity for transepithelial transport of Na + and HCO3 -in the choroid plexus.