Effect of altitude on brain intracellular pH and inorganic phosphate levels

Abstract

Normal brain activity is associated with task-related pH changes. Although central nervous system syndromes associated with significant acidosis and alkalosis are well understood, the effects of less dramatic and chronic changes in brain pH are uncertain. One environmental factor known to alter brain pH is the extreme, acute change in altitude encountered by mountaineers. However, the effect of long-term exposure to moderate altitude has not been studied. The aim of this two-site study was to measure brain intracellular pH and phosphate-bearing metabolite levels at two altitudes in healthy volunteers, using phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS). Increased brain pH and reduced inorganic phosphate (Pi) levels were found in healthy subjects who were long-term residents of Salt Lake City, UT (4720ft/1438m), compared with residents of Belmont, MA (20ft/6m). Brain intracellular pH at the altitude of 4720ft was more alkaline than that observed near sea level. In addition, the ratio of inorganic phosphate to total phosphate signal also shifted toward lower values in the Salt Lake City region compared with the Belmont area. These results suggest that long-term residence at moderate altitude is associated with brain chemical changes.

Keywords: Altitude; Hypoxia; Spectroscopy.

Fig. 1

(a) Region of interest (ROI) indicated by yellow boxes along three planes. Six outer saturation band were added to remove any signal from outside of ROI. (b) Representative ³¹P magnetic resonance spectrum. PCr, phosphocreatine; NTP, Nucleoside triphosphate; PME, phosphomonoester; PDE, phosphodiester; Pi, inorganic phosphate.

Fig. 2

(a) Scatter plot of brain intracellular pH values measured in Salt Lake City, UT, and Belmont, MA. The horizontal line represents the mean pH value in each group. (b) Scatter plot of the brain Pi levels at both sites.

Fig. 3

(a) Simulated pH versus signal-to-noise ratio (SNR). pH0 is computed from a noise-free spectrum, which is plotted as a dotted line. Simulated pH values with standard deviations are represented with open-diamond shaped markers. (b) pH standard deviation with respect to SNR in simulation.

Fig. 4

(a) Spectral overlap in data acquired from scanners in Salt Lake City and Belmont. (b) Zoom-in overlapping spectrum at methylphosphonic acid peak position in (a). (c) Zoom-in overlapping spectrum at phosphocholine and inorganic phosphate. MPA, methylphosphonic acid; PC, phosphocholine; Pi, inorganic phosphate.