Effects of chronic continuous hypoxia on the expression of SLC4A8 (NDCBE) in neonatal versus adult mouse brain

Na-coupled HCO3 transporters (NCBTs) play important roles in brain pH regulation. One NCBT, the Na-driven Cl-HCO3 exchanger (SLC4A8 or NDCBE), appears to be the major regulator of intracellular pH (pHi), at least in some hippocampal pyramidal neurons. NDCBE is widely expressed throughout the central nervous system in rodent brain. In a previous study, it has been demonstrated that CCH decreases the abundance of NBCn1 and NBCn2 proteins in four regions of the mouse brain: cerebral cortex (CX), subcortex (SCX), cerebellum (CB), and hippocampus (HC). Here we report the effect of CCH (11% O2) on the expression of NDCBE protein in mouse brain. Neonates (beginning at age P2) or adult mice (beginning at P90) were subjected to either normoxia or CCH for durations of 14 or 28 days. Membrane-protein levels were assessed by western blotting using our polyclonal antibody directed against NDCBE. In neonates, CCH significantly decreased NDCBE expression in HC after 14 days and SCX after 28 days, but had no significant effect for other combinations of region/duration. In adults, however, CCH significantly decreased (by 20–50%) the expression of NDCBE in all four brain regions, both with 14 and 28 day duration. Thus, the mouse brain exhibits marked developmental differences in the response of NDCBE protein expression to CCH. We hypothesize that decreases in adult NDCBE protein levels, which are probably out of proportion to the decreases in other proteins, may be part of an adaptive response that reduces energy consumption and/or stabilizes brain pHi. The smaller or absent responses in the young animals could be related to neonatal hypoxia tolerance.