TY - JOUR
T1 - NH4Cl-induced metabolic acidosis increases the abundance of HCO3 - transporters in the choroid plexus of mice
AU - Johnsen, Laura Øllegaard
AU - Sigad, Ahmed
AU - Friis, Kathrine Abildskov
AU - Berg, Peder Matzen
AU - Damkier, Helle Hasager
N1 - Copyright © 2024 Johnsen, Sigad, Friis, Berg and Damkier.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - HCO transporter
KW - SLC4A
KW - acidosis
KW - cerebrospinal fluid
KW - choroid plexus
UR - http://www.scopus.com/inward/record.url?scp=85208618636&partnerID=8YFLogxK
U2 - 10.3389/fphys.2024.1491793
DO - 10.3389/fphys.2024.1491793
M3 - Journal article
C2 - 39497701
SN - 1664-042X
VL - 15
JO - Frontiers in Physiology
JF - Frontiers in Physiology
M1 - 1491793
ER -