Photoperiod Manipulation Reveals a Light-Driven Component to Daily Patterns of Ventilation in Male C57Bl/6J Mice

Abstract

Obstructive sleep apnea is a common sleep disorder that increases risk for cardiovascular disease and mortality. The severity of sleep-disordered breathing in obstructive sleep apnea patients fluctuates with the seasons, opening the possibility that seasonal changes in light duration, or photoperiod, can influence mechanisms of breathing. Photoperiod can have profound effects on internal timekeeping and can reshape metabolic rhythms in mammals. While the daily rhythm in ventilation is largely shaped by the metabolic rate, less is known about whether ventilatory rhythms are altered in accordance with metabolism under different photoperiods. Here, we investigate the relationship between ventilation and metabolism under different photoperiods using whole-body plethysmography and indirect calorimetry. We find that the daily timing of ventilation is chiefly synchronized to dark onset and that light cues are important for maintaining daily ventilatory rhythms. Moreover, changes in ventilatory patterns are not paralleled by changes in oxygen consumption, energy expenditure, or respiratory exchange rate under different photoperiods. We conclude that ventilatory patterns are not only shaped by the metabolic rate and circadian timing but are also influenced by other light-driven factors. Collectively, these findings have clinical implications for the seasonal variations in sleep-disordered breathing found in individuals with obstructive sleep apnea.

The Molecular Circadian Clock of Phox2b-expressing Cells Drives Daily Variation of the Hypoxic but Not Hypercapnic Ventilatory Response in Mice

“…The molecular clock within the respiratory rhythm generator itself may contribute to the daily V E rhythm, as daily ventilation cycles seem predominantly driven by respiratory rate rather than tidal volume. 3 , 4 Moreover, it is unknown whether clock genes in other respiratory structures such as the cervical spinal cord and diaphragm, 13 or the lungs/airway 29 , 30 impact the daily rhythm in V E . Molecular clock dysfunction in any number of these non-Phox2b structures may contribute to the disrupted V E rhythm observed in global BMAL1 KO mice, warranting further investigation.…”

In light of breathing: environmental light is an important modulator of breathing with clinical implications

“…For example, minute ventilation, the product of respiratory rate and tidal volume, exhibits a daily rhythm that peaks during the active phase in rodents ( Stephenson et al, 2001 ; Seifert and Mortola, 2002 ; Purnell and Buchanan, 2020 ; Jones et al, 2021 ) and humans ( Bosco et al, 2003 ; Adamczyk et al, 2008 ). The daily rhythm in breathing can be phase shifted by acute perturbation of the light:dark cycle ( Mortola, 2007 ) and, in some instances ( Spengler et al, 2000 ; Jones et al, 2021 ), but not all ( Bosco et al, 2003 ), may be weakened by an absence of light cues. Thus, the daily rhythm in breathing is fundamentally organized by the external light environment.…”

“…Light duration/availability changes seasonally in many locations of the world, which can alter various aspects of circadian physiology ( Coomans et al, 2015 ). It was recently demonstrated in C57Bl/6 J mice that altering light duration to mimic seasonal changes in light availability while preserving the endogenous circadian period leads to changes in the respiratory pattern across the day and weakens the relationship between ventilation and metabolism in a time-dependent manner ( Jones et al, 2021 ). Indeed, mice housed under short days with only 5 h of light demonstrate a daily rhythm in minute ventilation that is controlled by tidal volume rather than the normally prevailing respiratory rate.…”

“…Additionally, time-dependent differences were observed under the short day after normalizing ventilation to metabolic rate, suggesting some dissociation of minute ventilation and metabolism across the day. In turn, mice housed on longer days with 19 h of light demonstrate a non-detectable rhythm in minute ventilation due to more variable breathing during the light phase ( Jones et al, 2021 ). These findings point to a role of seasonal light duration in reorganizing daily respiratory patterns.…”

“…For example, an observable daily rhythm in breathing persists even when controlling for sleep–wake state ( Stephenson et al, 2001 ) and activity level ( Seifert and Mortola, 2002 ). Additionally, rhythms in body temperature and metabolic rate can be phase-uncoupled from breathing under situations of light perturbation ( Spengler et al, 2000 ; Mortola, 2007 ; Jones et al, 2021 ). Therefore, SCN-dictated behaviors alone seem insufficient to fully organize the daily rhythm in breathing.…”