Serotonin and Corticosterone Rhythms in Mice Exposed to Cigarette Smoke and in Patients with COPD: Implication for COPD-Associated Neuropathogenesis

Abstract

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD.

Time-of-Day Dictates Transcriptional Inflammatory Responses to Cytotoxic Chemotherapy

“…As sleep disruption elicits an inflammatory response2627, this may have contributed to the enhanced splenic inflammation observed in animals injected at ZT 2. Additionally, glucocorticoid concentrations peak during the early active phase in nocturnal rodents28, and they are negative regulators of inflammation, acting through multiple mechanisms2930. Therefore, elevated baseline concentrations of glucocorticoids in mice injected at ZT 14 may have contributed to the dampened inflammatory response observed in the spleen, a pattern observed in the present study (Fig.…”

Disruption of Sirtuin 1–Mediated Control of Circadian Molecular Clock and Inflammation in Chronic Obstructive Pulmonary Disease

“…All subjects and patients provided written informed consent. The clinical characteristics of smokers, nonsmokers, and patients with COPD are presented in Table 1, and plasma from these subjects was used for hormone measurement in our recent report (20). Resected peripheral lungs were used as described previously (13,15).…”

“…Twenty-four hours after seeding, The clinical characteristics of smokers, nonsmokers, and patients with COPD included in the study are presented in our recent report (20).…”

Morphine Addiction is Tolerated Better in Socialized Male Rats

“…So it seems an increase in corticosterone may have an adverse effect or is not enough for the restoration of mood disorder. Also, reduce in neurogenesis may have serious adverse effect on mood and also neurotransmitter deregulation like serotonin is responsible for depression (Sundar et al, 2014). As noted, reduction of memory is also responsible for relapse.…”