Artificial night illumination disrupts sleep, and attenuates mood and learning in diurnal animals: evidence from behavior and gene expression studies in zebra finches.

This study investigated the effects of an illuminated night on sleep, mood, and cognitive performance in non-seasonal diurnal zebra finches that were exposed for 6 weeks to an ecologically relevant dimly lit night (12L:12dLAN; 150 lx: 5 lx) with controls on the dark night (12L:12D; 150 lx: < 0.01 lx). Food and water were provided ad libitum. Under dLAN (dim light at night), birds showed disrupted nocturnal (frequent awakenings) and overall decreased sleep duration. They also exhibited a compromised novel object exploration, a marker of the bird's mood state, and committed more errors, took significantly longer duration to learn with low retrieval performance of the learned task when tested for a color-discrimination (learning) task under the dLAN. Further, compared to controls, there was reduced mRNA expression level of genes involved in the neurogenesis, neural plasticity (bdnf, dcx and egr1) and motivation (th, drd2, taar1 and htr2c; dopamine synthesis and signaling genes) in the brain (hippocampus (HP), nidopallium caudolaterale (NCL), and midbrain) of birds under dLAN. These results show concurrent negative behavioral and molecular neural effects of the dimly illuminated nights, and provide insights into the possible impact on sleep and mental health in diurnal species inhabiting an increasingly urbanized ecosystem.

Exposure to dim light at night alters daily rhythms of glucose and lipid metabolism in rats.

Nocturnal light pollution has been rapidly increasing during the last decades and even though dim artificial light at night (ALAN) has been associated with metabolic diseases, its mechanism is still far from clear. Therefore, the aim of our study was to thoroughly analyze the effects of ALAN on energy metabolism, metabolites, metabolic hormones, and gene expression. Male Wistar rats were kept in either the standard light:dark (12:12) cycle or exposed to ALAN (∼2 lx) during the whole 12-h dark phase for 2 weeks. Energy metabolism was measured in metabolic cages. In addition, we measured plasma and hepatic metabolites, clock and metabolic gene expression in the liver and epididymal adipose tissue, and plasma hormone levels. In ALAN rats, we observed an unexpected transitory daytime peak of locomotor activity and a suppression of the peak in locomotor activity at the beginning of the dark period. These changes were mirrored in the respiratory exchange ratio. Plasma metabolites became arrhythmic, and plasma and hepatic cholesterol levels were increased. Lost rhythmicity of metabolites was associated with disrupted behavioral rhythms and expression of metabolic genes. In the liver, the rhythms of metabolic sensors were either phase-advanced (Ppara, Pgc1a, Nampt) or arrhythmic (Sirt1, Lxra) after ALAN. The rhythmic pattern of Ppara and Sirt1 was abolished in the adipose tissue. In the liver, the amplitude of the daily rhythm in glycogen content was attenuated, the Glut2 rhythm was phase-advanced and Foxo1 lost its daily rhythmicity. Moreover, hepatic Foxo1 and Gck were up-regulated after ALAN. Interestingly, several parameters of lipid metabolism gained rhythmicity (adiponectin, Hmgcs2, Lpl, Srebf1c) in the liver, whereas Noct became arrhythmic in the adipose tissue. Peripheral clock genes maintained their robust oscillations with small shifts in their acrophases. Our data show that even a low level of ALAN can induce changes in the daily pattern of behavior and energy metabolism, and disturb daily rhythms of genes encoding key metabolic sensors and components of metabolic pathways in the liver and adipose tissue. Disturbed metabolic rhythms by ALAN could represent a serious risk factor for the development and progression of metabolic diseases.

External light-dark cycle shapes gut microbiota through intrinsically photosensitive retinal ganglion cells.

Gut microbiota are involved in many physiological functions such as metabolism, brain development, and neurodegenerative diseases. Many microbes in the digestive tract do not maintain a constant level of their relative abundance but show daily oscillations under normal conditions. Recent evidence indicates that chronic jetlag, constant darkness, or deletion of the circadian core gene can alter the composition of gut microbiota and dampen the daily oscillation of gut microbes. However, the neuronal circuit responsible for modulating gut microbiota remained unclear. Using genetic mouse models and 16s rRNA metagenomic analysis, we find that light-dark cycle information transmitted by the intrinsically photosensitive retinal ganglion cells (ipRGCs) is essential for daily oscillations of gut microbes under temporal restricted high-fat diet conditions. Furthermore, aberrant light exposure such as dim light at night (dLAN) can alter the composition, relative abundance, and daily oscillations of gut microbiota. Together, our results indicate that external light-dark cycle information can modulate gut microbiota in the direction from the brain to the gut via the sensory system.

Artificial Light at Night Reduces Anxiety-like Behavior in Female Mice with Exacerbated Mammary Tumor Growth.

Artificial light at night (ALAN) is a pervasive phenomenon. Although initially assumed to be innocuous, recent research has demonstrated its deleterious effects on physiology and behavior. Exposure to ALAN is associated with disruptions to sleep/wake cycles, development of mood disorders, metabolic disorders, and cancer. However, the influence of ALAN on affective behavior in tumor-bearing mice has not been investigated. We hypothesize that exposure to ALAN accelerates mammary tumor growth and predict that ALAN exacerbates negative affective behaviors in tumor-bearing mice. Adult (>8 weeks) female C3H mice received a unilateral orthotropic injection of FM3A mouse mammary carcinoma cells (1.0 × 105 in 100 µL) into the fourth inguinal mammary gland. Nineteen days after tumor inoculation, mice were tested for sucrose preference (anhedonia-like behavior). The following day, mice were subjected to an open field test (anxiety-like behavior), followed by forced swim testing (depressive-like behavior). Regardless of tumor status, mice housed in ALAN increased body mass through the first ten days. Tumor-bearing ALAN-housed mice demonstrated reduced latency to tumor onset (day 5) and increased terminal tumor volume (day 21). Exposure to ALAN reduced sucrose preference independent of tumor status. Additionally, tumor-bearing mice housed in dark nights demonstrated significantly increased anxiety-like behavior that was normalized via housing in ALAN. Together, these data reaffirm the negative effects of ALAN on tumorigenesis and demonstrate the potential anxiolytic effect of ALAN in the presence of mammary tumors.

Aberrant Lighting Causes Anxiety-like Behavior in Mice but Curcumin Ameliorates the Symptoms.

In the modern research field, laboratory animals are constantly kept under artificial lighting conditions. However, recent studies have shown the effect of artificial light on animal behavior and metabolism. In the present study on mice, following three weeks of housing in dim light at night (dLAN; 5lux) and complete darkness (DD; 0lux), we monitored the effect on body weight, daily food intake, anxiety-like behavior by employing the open field test, and expression of the period (PER1) gene. We also studied the effect of oral administration of different concentrations of curcumin (50, 100, and 150 mg/kg) for three weeks in the same mice and monitored these parameters. The exposure to dLAN had significantly increased the anxiety-like behavior and body weight possibly through the altered metabolism in mice, whereas exposure to DD caused increased anxiety but no significant difference in weight gain. Moreover, the expression of the PER1 gene involved in sleep was also found to be decreased in the aberrant light conditions (dLAN and DD). Although the treatment of curcumin had no effect on body weight, it ameliorated the anxiety-like behavior possibly by modulating the expression of the PER1 gene. Thus, alteration in the light/dark cycle had a negative effect on laboratory animals on the body weight and emotions of animals. The present study identifies the risk factors associated with artificial lighting systems on the behavior of laboratory animals and the ameliorative effects of curcumin, with a focus on anxiety-like behavior.

Sleep Network Deterioration as a Function of Dim-Light-At-Night Exposure Duration in a Mouse Model.

Artificial light, despite its widespread and valuable use, has been associated with deterioration of health and well-being, including altered circadian timing and sleep disturbances, particularly in nocturnal exposure. Recent findings from our lab reveal significant sleep and sleep electroencephalogram (EEG) changes owing to three months exposure to dim-light-at-night (DLAN). Aiming to further explore the detrimental effects of DLAN exposure, in the present study, we continuously recorded sleep EEG and the electromyogram for baseline 24-h and following 6-h sleep deprivation in a varied DLAN duration scheme. C57BL/6J mice were exposed to a 12:12 h light:DLAN cycle (75lux:5lux) vs. a 12:12 h light:dark cycle (75lux:0lux) for one day, one week, and one month. Our results show that sleep was already affected by a mere day of DLAN exposure with additional complications emerging with increasing DLAN exposure duration, such as the gradual delay of the daily 24-h vigilance state rhythms. We conducted detrended fluctuation analysis (DFA) on the locomotor activity data following 1-month and 3-month DLAN exposure, and a significantly less healthy rest-activity pattern, based on the decreased alpha values, was found in both conditions compared to the control light-dark. Taking into account the behavioral, sleep and the sleep EEG parameters, our data suggest that DLAN exposure, even in the shortest duration, induces deleterious effects; nevertheless, potential compensatory mechanisms render the organism partly adjustable and able to cope. We think that, for this reason, our data do not always depict linear divergence among groups, as compared with control conditions. Chronic DLAN exposure impacts the sleep regulatory system, but also brain integrity, diminishing its adaptability and reactivity, especially apparent in the sleep EEG alterations and particular low alpha values following DFA.

Differential Effects of Constant Light and Dim Light at Night on the Circadian Control of Metabolism and Behavior.

The disruption of circadian rhythms by environmental conditions can induce alterations in body homeostasis, from behavior to metabolism. The light:dark cycle is the most reliable environmental agent, which entrains circadian rhythms, although its credibility has decreased because of the extensive use of artificial light at night. Light pollution can compromise performance and health, but underlying mechanisms are not fully understood. The present review assesses the consequences induced by constant light (LL) in comparison with dim light at night (dLAN) on the circadian control of metabolism and behavior in rodents, since such an approach can identify the key mechanisms of chronodisruption. Data suggest that the effects of LL are more pronounced compared to dLAN and are directly related to the light level and duration of exposure. Dim LAN reduces nocturnal melatonin levels, similarly to LL, but the consequences on the rhythms of corticosterone and behavioral traits are not uniform and an improved quantification of the disrupted rhythms is needed. Metabolism is under strong circadian control and its disruption can lead to various pathologies. Moreover, metabolism is not only an output, but some metabolites and peripheral signal molecules can feedback on the circadian clockwork and either stabilize or amplify its desynchronization.

Sleep in unnatural times: illuminated night negatively affects sleep and associated hypothalamic gene expressions in diurnal zebra finches.

We investigated the effects of exposure at ecologically relevant levels of dim light at night (dLAN) on sleep and the 24 h hypothalamic expression pattern of genes involved in the circadian timing (per2, bmal1, reverb-ß, cry1, ror-α, clock) and sleep regulatory pathways (cytokines: tlr4, tnf-α, il-1ß, nos; Ca2+-dependent pathway: camk2, sik3, nr3a; cholinergic receptor, achm3) in diurnal female zebra finches. Birds were exposed to 12 h light (150 lux) coupled with 12 h of absolute darkness or of 5 lux dim light for three weeks. dLAN fragmented the nocturnal sleep in reduced bouts, and caused sleep loss as evidenced by reduced plasma oxalate levels. Under dLAN, the 24 h rhythm of per2, but not bmal1 or reverb-ß, showed a reduced amplitude and altered peak expression time; however, clock, ror-α and cry1 expressions showed an abolition of the 24 h rhythm. Decreased tlr4, il-1ß and nos, and the lack of diurnal difference in achm3 messenger RNA levels suggested an attenuated inhibition of the arousal system (hence, awake state promotion) under dLAN. Similarly, changes in camk2, sik3 and nr3a expressions suggested dLAN-effects on Ca2+-dependent sleep-inducing pathways. These results demonstrate dLAN-induced negative effects on sleep and associated hypothalamic molecular pathways, and provide insights into health risks of illuminated night exposures to diurnal animals.

Effects of Chronic Dim-light-at-night Exposure on Sleep in Young and Aged Mice.

Dim-light-at-night (DLAN) exposure is associated with health problems, such as metabolic disruptions, immunological modulations, oxidative stress, sleep problems, and altered circadian timing. Neurophysiological parameters, including sleep patterns, are altered in the course of aging in a similar way. Here, we investigated the effect of chronic (three months) DLAN exposure (12 L:12 Dim-light, 75:5 lux) on sleep and the sleep electroencephalogram (EEG), and rest-activity behavior in young (6-month-old, n = 9) and aged (18- n = 8, 24-month-old, n = 6) C57BL/6J mice and compared with age-matched controls (n = 11, n = 9 and n = 8, respectively). We recorded the EEG and electromyogram continuously for 48-h and conducted a 6-h sleep-deprivation. A delay in the phase angle of entrainment of locomotor activity and daily vigilance state rhythms was apparent in mice following DLAN exposure, throughout the whole age spectrum, rendering sleep characteristics similar among the three age DLAN groups and significantly different from the age-matched controls. Notably, slow-wave-activity in NREM sleep (SWA, EEG power density in 0.5-4.0 Hz) was differentially altered in young and aged DLAN mice. Particularly, SWA increased as a function of age, which was further accentuated following DLAN exposure. However, this was not found in the young DLAN animals, which were characterized by the lowest SWA levels. Concluding, long-term DLAN exposure induced more pronounced alterations in the sleep architecture of young mice, towards an aging phenotype, while it enhanced age-associated sleep changes in the older groups. Our data suggest that irrespective of age, chronic DLAN exposure deteriorates sleep behavior and may consequently impact general health.

Illuminated night alters behaviour and negatively affects physiology and metabolism in diurnal zebra finches.

Light at night (LAN) negatively impacts the behaviour and physiology; however, very little is known about molecular correlates of LAN-induced effects in diurnal animals. Here, we assessed LAN-induced effects on behaviour and physiology, and examined molecular changes in the liver of diurnal zebra finches (Taeniopygia guttata). Birds were exposed to dim LAN (dLAN: 12L = 150 lux: 12D = 5 lux), with controls on 12L (150 lux): 12D (0 lux). dLAN altered daily activity-rest and eating patterns, induced nocturnal eating and caused body fattening and weight gain, and reduced nocturnal melatonin levels. Concomitant increased nighttime glucose levels, decreased daytime thyroxine and triglycerides levels, and hepatic lipid accumulation suggested the impairment of metabolism under dLAN. Transcriptional assays evidenced dLAN-induced negative effects on metabolism in the liver, the site of metabolic homeostasis. Particularly, increased g6pc and foxo1 mRNA expressions suggested an enhanced gluconeogenesis, while increased egr1 and star expressions suggested enhanced cholesterol biosynthesis and lipid metabolism, respectively. Similarly, overexpressed sirt1 indicated protection from the metabolic damage due to elevated gluconeogenesis and cholesterol biosynthesis under dLAN. However, no effect on genes involved in lipogenesis (fasn) and insulin signalling pathway (socs3 and insig1) might indicate for the post transcriptional/post translational modification effects or the involvement of other genetic pathways in LAN-induced effects. We also found daily rhythm in the hepatic expression of selected clock and clock-controlled genes (per2, bmal1 and reverb-beta), with an elevated mesor and amplitude of per2 oscillation, suggesting a role of per2 in the liver metabolism. These results demonstrate dLAN-induced negative effects on the behaviour and physiology, and provide molecular insights into metabolic risks of the exposure to illuminated nights to diurnal animals including humans in an urban setting.

Prior exposure to dim light at night impairs dermal wound healing in female C57BL/6 mice.

Artificial light at night (LAN) is a pervasive phenomenon in today's society, and the detrimental consequences of LAN exposure are becoming apparent. LAN is associated with the increased incidence of metabolic disorders, cancers, mood alterations, and immune dysfunction in mammals. Consequently, we examined the effects of dim LAN (DLAN) on wound healing. Female C57BL/6 mice were housed for 3 weeks in DLAN or LD conditions prior to wounding. Following wounding, mice were maintained in either their previous light conditions or switched to the opposite lighting conditions for 3 weeks. DLAN prior to wounding impaired healing; specifically, mice in DLAN/DLAN had significantly larger wounds on day 8. Additionally, mice in DLAN/LD had significantly larger wounds on days 5, 7, 8, and 9, and increased average time to closure. These data demonstrate a potential harmful effect of DLAN on wound healing that should be considered and may represent a target for therapeutic intervention.

Impact of Exposure to Dim Light at Night on Sleep in Female and Comparison with Male Subjects.

OBJECTIVE: Light pollution has become a social and health issue. We performed an experimental study to investigate impact of dim light at night (dLAN) on sleep in female subjects, with measurement of salivary melatonin. METHODS: The 25 female subjects (Group A: 12; Group B: 13 subjects) underwent a nocturnal polysomnography (NPSG) session with no light (Night 1) followed by an NPSG session randomly assigned to two conditions (Group A: 5; Group B: 10 lux) during a whole night of sleep (Night 2). Salivary melatonin was measured before and after sleep on each night. For further investigation, the female and male subjects of our previous study were collected (48 subjects), and differences according to gender were compared. RESULTS: dLAN during sleep was significantly associated with decreased total sleep time (TST; F=4.818, p=0.039), sleep efficiency (SE; F=5.072, p=0.034), and Stage R latency (F=4.664, p=0.041) for female subjects, and decreased TST (F=14.971, p<0.001) and SE (F=7.687, p=0.008), and increased wake time after sleep onset (F=6.322, p=0.015) and Stage R (F=5.031, p=0.03), with a night-group interaction (F=4.579, p=0.038) for total sample. However, no significant melatonin changes. There was no significant gender difference of the impact of dLAN on sleep, showing the negative changes in the amount and quality of sleep and the increase in REM sleep in the both gender group under 10 lux condition. CONCLUSION: We found a negative impact of exposure to dLAN on sleep in female as well as in merged subjects. REM sleep showed a pronounced increase under 10 lux than under 5 lux in merged subjects, suggesting the possibility of subtle influences of dLAN on REM sleep.

Short-term exposure to dim light at night disrupts rhythmic behaviors and causes neurodegeneration in fly models of tauopathy and Alzheimer's disease.

The accumulation and aggregation of phosphorylated tau proteins in the brain are the hallmarks for the onset of Alzheimer's disease (AD). In addition, disruptions in circadian rhythms (CRs) with altered sleep-wake cycles, dysregulation of locomotion, and increased memory defects have been reported in patients with AD. Drosophila flies that have an overexpression of human tau protein in neurons exhibit most of the symptoms of human patients with AD, including locomotion defects and neurodegeneration. Using the fly model for tauopathy/AD, we investigated the effects of an exposure to dim light at night on AD symptoms. We used a light intensity of 10 lux, which is considered the lower limit of light pollution in many countries. After the tauopathy flies were exposed to the dim light at night for 3 days, the flies showed disrupted CRs, altered sleep-wake cycles due to increased pTau proteins and neurodegeneration, in the brains of the AD flies. The results indicate that the nighttime exposure of tauopathy/AD model Drosophila flies to dim light disrupted CR and sleep-wake behavior and promoted neurodegeneration.

Impact of Exposure to Dim Light at Night on Sleep in Female and Comparison with Male Subjects

OBJECTIVE: Light pollution has become a social and health issue. We performed an experimental study to investigate impact of dim light at night (dLAN) on sleep in female subjects, with measurement of salivary melatonin. METHODS: The 25 female subjects (Group A: 12; Group B: 13 subjects) underwent a nocturnal polysomnography (NPSG) session with no light (Night 1) followed by an NPSG session randomly assigned to two conditions (Group A: 5; Group B: 10 lux) during a whole night of sleep (Night 2). Salivary melatonin was measured before and after sleep on each night. For further investigation, the female and male subjects of our previous study were collected (48 subjects), and differences according to gender were compared. RESULTS: dLAN during sleep was significantly associated with decreased total sleep time (TST; F=4.818, p=0.039), sleep efficiency (SE; F=5.072, p=0.034), and Stage R latency (F=4.664, p=0.041) for female subjects, and decreased TST (F=14.971, p<0.001) and SE (F=7.687, p=0.008), and increased wake time after sleep onset (F=6.322, p=0.015) and Stage R (F=5.031, p=0.03), with a night-group interaction (F=4.579, p=0.038) for total sample. However, no significant melatonin changes. There was no significant gender difference of the impact of dLAN on sleep, showing the negative changes in the amount and quality of sleep and the increase in rapid eye movement (REM) sleep in the both gender group under 10 lux condition. CONCLUSION: We found a negative impact of exposure to dLAN on sleep in female as well as in merged subjects. REM sleep showed a pronounced increase under 10 lux than under 5 lux in merged subjects, suggesting the possibility of subtle influences of dLAN on REM sleep.

Dim light at night disrupts the short-day response in Siberian hamsters.

Photoperiodic regulation of physiology, morphology, and behavior is crucial for many animals to survive seasonally variable conditions unfavorable for reproduction and survival. The photoperiodic response in mammals is mediated by nocturnal secretion of melatonin under the control of a circadian clock. However, artificial light at night caused by recent urbanization may disrupt the circadian clock, as well as the photoperiodic response by blunting melatonin secretion. Here we examined the effect of dim light at night (dLAN) (5lux of light during the dark phase) on locomotor activity rhythms and short-day regulation of reproduction, body mass, pelage properties, and immune responses of male Siberian hamsters. Short-day animals reduced gonadal and body mass, decreased spermatid nuclei and sperm numbers, molted to a whiter pelage, and increased pelage density compared to long-day animals. However, animals that experienced short days with dLAN did not show these short-day responses. Moreover, short-day specific immune responses were altered in dLAN conditions. The nocturnal activity pattern was blunted in dLAN hamsters, consistent with the observation that dLAN changed expression of the circadian clock gene, Period1. In addition, we demonstrated that expression levels of genes implicated in the photoperiodic response, Mel-1a melatonin receptor, Eyes absent 3, thyroid stimulating hormone receptor, gonadotropin-releasing hormone, and gonadotropin-inhibitory hormone, were higher in dLAN animals than those in short-day animals. These results suggest that dLAN disturbs the circadian clock function and affects the molecular mechanisms of the photoperiodic response.