Differential Na+/K+ Pump Isoform Expression in Higher and Lower Brain Regions of the Mouse
It has been demonstrated both clinically and experimentally that the higher brain is highly vulnerable to ischemia, while the lower brain is comparatively resilient. Discovering how lower brain neurons naturally resist ischemic stress may help to design new strategies for improving higher brain survival following ischemia. Our laboratory has proposed that differential expression of Na+/K+-ATPase isoforms, the ion pumps responsible for maintaining the electrochemical gradients of neurons, may underlie this phenomenon. Specifically, the α3 isoform, but not the α1 isoform, possesses kinetic properties that allow it to function efficiently under low energy conditions, rendering it ischemia-resistant. The goal of this thesis was to characterize regional expression of Na+/K+-ATPase α1 and α3 isoforms in the brains of Aldh2+/+ and Aldh2-/- mice across the lifespan, under both baseline (naïve) and chronic unpredictable stress (CUS) conditions. Quantitative polymerase chain reaction was used to analyze mRNA expression levels of α1 and α3 isoforms within higher and lower brain regions of 5 – 7 month old and 15 – 19 month old naïve Aldh2+/+ and Aldh2-/- mice, as well as in 3 month old mice that underwent a 28-day CUS protocol, along with age-matched controls. In both young and aged naïve cohorts, the α3 isoform was proportionally more highly expressed in the brainstem compared to the neocortex, while α1 was proportionally more highly expressed in the neocortex and less so, in the hippocampus, compared to the brainstem. Exposure to the CUS protocol did not significantly alter α1 or α3 mRNA expression in any brain region compared to controls. Stress mice exhibited regional differences in α1 and α3 expression that were consistent with the results in naïve animals. There were no significant effects of genotype or sex on the expression of either isoform. Parallel studies from our laboratory have shown that protein expression correlates with mRNA expression. Future work in our laboratory will investigate how α1 or α3 expression may change and protect neurons in response to acute ischemia.