Prolonged red light disrupts circadian hormones associated with phrenic neuroplasticity
Authors: Budd Lucas , Mitchell Gordon , Marciante Alexandria 
Published: May 2023

Neurodegenerative disease and spinal cord injury impair breathing ability, significantly impacting the quality and duration of life. New therapeutic interventions for these conditions aim to improve respiratory function by using intermittent exposure to periods of low oxygen (acute intermittent hypoxia; AIH). AIH elicits one form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF) via competing cellular mechanisms initiated by serotonin and adenosine, respectively. Circadian rhythm and the daily rest/active cycle have recently been shown to modulate the serotonin vs adenosine balance and pLTF. Melatonin and corticosterone are light-sensitive hormones that regulate neuroplasticity and molecules necessary for some forms of pLTF, particularly adenosine. Since the impact of these light-sensitive hormones on pLTF has not been directly investigated, we performed a preparatory investigation concerning the impact of dim red light on daily cycles. We hypothesized that prolonged exposure to low-intensity red light during the active/dark phase (rLEN) impacts light-sensitive hormones. Male Sprague-Dawley rats (3-4 months) were housed in a 12 on/12 off light cycle in 3 different light conditions: 1) normal-cycle (light onset 0700h; n=6); 2) reverse-cycle (light onset 1900h; n=8); or 3) reverse-cycle with rLEN (32 Lux) during the dark phase (light onset 1900h; n=6). Serum samples were collected at mid time-points in the daily rest/active cycle ( i.e. 12PM and 12AM). Competitive ELISAs were used to quantify serum melatonin and corticosterone levels; an adenosine assay was used to quantify spinal adenosine. During the midactive phase, melatonin levels were significantly reduced in rLEN rats (63pg/mL; p<0.050) vs rats in normal- (104pg/mL) and reverse- (107pg/mL) cycle housing. Spinal adenosine levels were similar between normal- (15uM) and reverse- (20uM) cycled rats in the midactive phase, but were significantly lower in the rLEN rats (2uM; p<0.001). Melatonin and spinal adenosine levels during midrest were not different between groups. Corticosterone levels during the midactive phase were similar between normal- (46.6ng/mL) and reverse- (34.3ng/mL) cycled rats, but were significantly lower with rLEN (23.5ng/mL; p<0.050). Corticosterone during the midrest phase in the normal- (12ng/mL) and reverse- (12.4ng/mL) cycle were similar, but was significantly elevated in rLEN rats (25ng/mL; p=0.022). We also observed a shift in sleep behavior in rLEN rats. Thus: 1) rats housed in normal and reverse light cycle exhibit appropriate cycles in light-sensitive hormones; but 2) even low intensity rLEN during the active phase disrupts these light-sensitive & stress-related hormones. These data yield striking evidence for the need to limit rLEN exposure to rodent models, and may have important implications for the use of AIH as a therapeutic modality to improve breathing (or non-respiratory motor) function in people with disrupted circadian rhythms. Supported by: NIH HL147554, HL148030, T32HL134621-5 (ABM), the American Physiology Society (LRB) and the UF McKnight Brain Institute. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.