The Pattern of Breathing in Young Wild Type and Ts65Dn Mice During the Dark and Light Cycle

Abstract

Down syndrome (Ds) results from trisomy 21 and is the most common cause of mental retardation in the US. People with Ds display muscle weakness and cardiorespiratory complications that may contribute to their altered breathing. Ts65Dn mice, a model of Ds, have been shown to exhibit altered breathing at 12 months of age. It is unknown when breathing changes occur in these mice but it is hypothesized to be later in development based on muscle alterations reported in the literature. An additional study found hypoxemia to be more common in the dark vs. light cycle in Ts65Dn mice. We tested the hypothesis that 3‐month Ts65Dn mice would display an altered pattern of breathing compared to wild‐type (WT) mice, and that responses would differ between dark and light cycles. In order to test these hypotheses, unrestrained barometric plethysmography was used to quantify breathing frequency (breaths/min; BPM), tidal volume (TV; mL/breath) and minute ventilation (MV; mL/min) in 3‐month old Ts65Dn (n=3) and WT (n=4) mice. Mice were tested between hours 8–10 of the dark cycle and between hours 7–9 of the light cycle. Implantable LifeChips (Destron Fearing, Airport, TX) were used to monitor body temperature; changes of more than 1 degree were accounted for in the analyses. Ponemah software (Data Sciences International, St. Paul, MN) was used to analyze flow tracings during exposure to air (20.93% O2, balanced N2), hypoxia (10% O2, balanced N2), hypercapnia (5% CO2, balanced air) and hypoxic hypercapnia (10% O2, 5% CO2, balanced N2). Data are expressed as MEAN±SD; p<0.05; WT vs. Ts65Dn. Body weight was not different between WT and Ts65Dn mice (37.5±4.2 vs. 37.7±5.8g). The delta for dark minus light cycle were analyzed with repeated measures two‐way ANOVA, with strain and gas exposure as factors. An interaction between strain and gas exposures was found for MV and breathing frequency. No interaction was detected for TV. The delta for frequency are described for quiet breathing (12±7 vs. −3±36 BPM), hypoxia (6±31 vs. 8±15 BPM), hypercapnia (61±32 vs. 48±25 BPM), hypoxic hypercapnia (48±37 vs. 35±38 BPM) and recovery (−14±64 vs. 156±49 BPM). MV deltas are listed for quiet breathing (−0.9±21.9 vs. 20.8±33.8 mL/min), hypoxia (−0.9±38.8 vs. 24.9±21.9 mL/min), hypercapnia (32.5±72.3 vs. 71.1±68.1 mL/min), hypoxic hypercapnia (25.8±78.2 vs. 66.9±81.8 mL/min) and recovery (10.8±46.5 vs. 146.7±107.1 mL/min). Once more data are collected, the repeated measures two‐way ANOVA will be re‐run, and post‐hoc analysis will be performed for each gas exposure. Apnea count (no flow ≥0.5 sec) showed cycle (light/dark) and strain differences, along with a cycle by strain interaction. Light cycle apneas were more common (16±17/hr vs. 81±40/hr; WT vs. Ts65Dn) compared to the dark cycle (7±12/hr vs. 51±35/hr; WT vs. Ts65Dn); apneas were more prevalent in Ts65Dn mice overall. This preliminary study indicates the Ts65Dn mouse model may have a greater delta magnitude (dark minus light) when comparing the pattern of breathing to WT mice in dark and light cycles. The apnea count in Ts65Dn is suggestive of a lower neural drive to breath in these mice vs. WT. Additional data will be collected to identify if these initial findings continue in Ts65Dn and WT mice.Support or Funding InformationFunded by 1 R15 HD076379‐01A1, CNR supported by 1 R15 HD076379‐01A1S1.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.