NHCl-induced Metabolic Acidosis Increases the Abundance of HCO Transporters in the Choroid Plexus of Mice

Overview

Journal Front Physiol

Date 2024 Nov 5

PMID 39497701

Authors

Laura Ollegaard Johnsen

Ahmed Sigad

Kathrine Abildskov Friis

Peder Matzen Berg

Helle Hasager Damkier

Affiliations

Soon will be listed here.

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

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