Effect of inspired oxygen concentration on periodic breathing in methyl‐CpG‐binding protein 2 (Mecp2) deficient mice

Abstract

Rett syndrome (RTT) is characterized by periodic breathing (PB). The goal of this study was to determine if moderate hyperoxia or hypoxia affected the incidence and/or characteristics of PB in Mecp2+/− mice. Individual mice were exposed for 30 min to air, 40% or 12% oxygen. Respiratory pattern was monitored by telemetric measurement of pleural pressure. PB was defined as 3 or more periods of 3 to 20 incrementing then decrementing amplitude breaths separated by apneas. Hyperoxia increased incidence of PB in Mecp2+/− mice from 115.3 ± 27.5 to 219 ± 58.9 s and number of PB episodes from 8.1 ± 1.6 to 12.3 ± 2.4. Episode duration was the same. 40% oxygen increased A/V from 0.44 ± 0.04 to 0.58 ± 0.05. Hypoxia did not significantly affect the incidence (71.3 ± 31 vs 115.3 ± 27.5 sec), number of episodes (4.6 ± 1.6 vs 8.1 ± 1.6), period length nor A/V in Mecp2+/− mice. The duration of PB episodes was decreased in 12 % oxygen (10.2 ± 1.6 vs 14.1 ± 1.5 sec). This paradoxical effect of inspired oxygen concentration suggests that the increased loop gain in Mecp2+/− mice is not due to an augmented hypoxic drive from peripheral chemoreceptors. Rather the results suggest that this mouse model of RTT has an unbalanced contribution from excitatory and inhibitory inputs to inspiratory central neurons such that hyperoxic modulation of the inhibitory influences exacerbates their breathing instability. Support: FY06-314 March of Dimes