Article

Dim light at night attenuates circadian rhythms in the cardiovascular system and suppresses melatonin in rats

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Abstract

Aims: Cardiovascular parameters exhibit significant 24-h variability, which is coordinated by the suprachiasmatic nucleus (SCN), and light/dark cycles control SCN activity. We aimed to study the effects of light at night (ALAN; 1-2 lx) on cardiovascular system control in normotensive rats. Main methods: Heart rate (HR) and blood pressure (BP) were measured by telemetry during five weeks of ALAN exposure. From beat-to-beat telemetry data, we evaluated spontaneous baroreflex sensitivity (sBRS). After 2 (A2) and 5 (A5) weeks of ALAN, plasma melatonin concentrations and the response of BP and HR to norepinephrine administration were measured. The expression of endothelial nitric oxide synthase (eNOS) and endothelin-1 was determined in the aorta. Spontaneous exploratory behaviour was evaluated in an open-field test. Key findings: ALAN significantly suppressed the 24-h variability in the HR, BP, and sBRS after A2, although the parameters were partially restored after A5. The daily variability in the BP response to norepinephrine was reduced after A2 and restored after A5. ALAN increased the BP response to norepinephrine compared to the control after A5. Increased eNOS expression was found in arteries after A2 but not A5. Endothelin-1 expression was not affected by ALAN. Plasma melatonin levels were suppressed after A2 and A5. Spontaneous exploratory behaviour was reduced. Significance: ALAN decreased plasma melatonin and the 24-h variability in the haemodynamic parameters and increased the BP response to norepinephrine. A low intensity ALAN can suppress circadian control of the cardiovascular system with negative consequences on the anticipation of a load.

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... Cardiovascular disease remains a leading cause of death, and many cardiovascular variables (e.g., heart rate and arterial blood pressure) have day-night rhythms that cycle with a periodicity of ≈24 h 12 . The impact that light at night has on day-night rhythms in heart rate and blood pressure is only now being understood [13][14][15] . Data suggest that light at night decreases the amplitude of day-night heart rate and blood pressure rhythms in people and small animals but through distinct mechanisms 14 . ...
... Blood pressure dipping is an important clinical marker for cardiovascular disease in people. Generally, the blood pressure is lower during the night in people and during the day in mice 15,18,32,33 . Classically, a >10% decrease in resting blood pressure dipping is considered healthy, and the loss or decrease in blood pressure dipping has been suggested to be an index for future target organ damage and risk for cardiovascular events. ...
... The concept that light at night decreases the amplitude in day-night rhythms of cardiovascular physiology is not new, nor is the concept that it is linked to increased cardiometabolic risk 4,10,[13][14][15] . A limitation of this study is that we did not include an experimental group for nighttime restricted feeding in mice housed in 12-hour light and dark cycles. ...
Article
Background: Light input to the suprachiasmatic nucleus entrains circadian rhythms in physiology and behavior to the day-night cycle. Exposure to light at night in people is associated with cardiometabolic disease. Pre-clinical studies show that artificial light at night, including at very low levels, disrupts day-night rhythms in activity, feeding behavior, heart rate, and blood pressure dipping. Hypothesis: Dim light at night (dLAN) disrupts day-night rhythms in feeding behavior to blunt day-night rhythms in autonomic input to the heart and blood pressure dipping. Methods: Mice (n=5-6/sex) in thermoneutral housing were implanted with telemetry probes to record heart rate, blood pressure, and core body temperature. Autonomic input to the heart was assessed by measuring heart rate and subtracting the temperature-dependent changes in the heart rate after pharmacological inhibition of muscarinic and β-adrenergic receptor activation. Mice were housed in 12 h light: 12 h dark cycles (LD, 200 lux: 0 lux) with ad libitum access to food (LD-ALF), subjected to 12 h light: 12 h dLAN cycles (dLAN-ALF; 200 lux: 5 lux) for two weeks, and then feeding was time-restricted (not calorically restricted) to the dLAN cycle (dLAN-RF). Data were extracted from Ponemah and Clocklab, and statistical analysis was done using GraphPad PRISM software. Results: Compared to LD-ALF mice, dLAN-ALF mice showed reduced amplitudes in day-night activity, feeding, heart rate, and blood pressure rhythms, with males more affected than females (p<0.001). dLAN-ALF male and female mice had decreased amplitudes in the day-night rhythms in autonomic input to the heart. In addition, dLAN-ALF male mice had less blood pressure dipping. dLAN-RF normalized autonomic input to the heart and heart rate in male and female mice (p<0.05, p<0.01, respectively). dLAN-RF also improved blood pressure dipping in male mice (p<0.001). dLAN-RF did not normalize activity rhythms. Conclusion: dLAN disrupts day-night rhythms in activity, feeding, heart rate, and blood pressure dipping in mice, with males being more impacted. Time-restricted feeding to the dLAN cycle normalizes autonomic input to the heart and blood pressure dipping. These data suggest that time-restricted feeding counteracts the light-at-night-induced circadian disruption of cardiovascular function.
... Cardiovascular disease remains a leading cause of death, and many cardiovascular variables (e.g., heart rate and arterial blood pressure) have day-night rhythms that cycle with a periodicity of ≈24 h 12 . The impact that light at night has on day-night rhythms in heart rate and blood pressure is only now being understood [13][14][15] . Data suggest that light at night decreases the amplitude of day-night heart rate and blood pressure rhythms in people and small animals but through distinct mechanisms 14 . ...
... Blood pressure dipping is an important clinical marker for cardiovascular disease in people. Generally, the blood pressure is lower during the night in people and during the day in mice 15,18,32,33 . Classically, a >10% decrease in resting blood pressure dipping is considered healthy, and the loss or decrease in blood pressure dipping has been suggested to be an index for future target organ damage and risk for cardiovascular events. ...
... The concept that light at night decreases the amplitude in day-night rhythms of cardiovascular physiology is not new, nor is the concept that it is linked to increased cardiometabolic risk 4,10,[13][14][15] . A limitation of this study is that we did not include an experimental group for nighttime restricted feeding in mice housed in 12-hour light and dark cycles. ...
Article
Full-text available
Shift work and artificial light at night disrupt the entrainment of endogenous circadian rhythms in physiology and behavior to the day-night cycle. We hypothesized that exposure to dim light at night (dLAN) disrupts feeding rhythms, leading to sex-specific changes in autonomic signaling and day-night heart rate and blood pressure rhythms. Compared to mice housed in 12-hour light/12-hour dark cycles, mice exposed to dLAN showed reduced amplitudes in day-night feeding, heart rate, and blood pressure rhythms. In female mice, dLAN reduced the amplitude of day-night cardiovascular rhythms by decreasing the relative sympathetic regulation at night, while in male mice, it did so by increasing the relative sympathetic regulation during the daytime. Time-restricted feeding to the dim light cycle reversed these autonomic changes in both sexes. We conclude that dLAN induces sex-specific changes in autonomic regulation of heart rate and blood pressure, and time-restricted feeding may represent a chronotherapeutic strategy to mitigate the cardiovascular impact of light at night.
... The biological clock generates circadian rhythms with an endogenous period of~24-h. Circadian rhythms are observed in behaviour, locomotor activity, metabolism, and many other physiological processes, including the cardiovascular system [1][2][3]. The main synchronisation factor of circadian rhythms is a regular light/dark (LD) cycle. ...
... Similar observations were found in animal models [11]. In rats, ALAN suppressed the 24-h variability of blood pressure and heart rate and reduced the amplitude and significance of their circadian rhythms [1]. At the same time, some individuals became arrhythmic even after 2 weeks of ALAN [12]. ...
... At the same time, some individuals became arrhythmic even after 2 weeks of ALAN [12]. Distinct from humans, in rats, ALAN suppressed sympathetic activity and altered baroreflex sensitivity [1,12], which may be associated with the observed haemodynamic changes. ...
Article
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Artificial light at night (ALAN) disrupts 24-h variability of blood pressure, but the molecular mechanisms underlying these effects are unknown. Therefore, we analysed the daily variability of pulse pressure, the maximum value of acceleration rate of aortic pressure (dP/dt(max)) measured by telemetry and protein expression in the thoracic aorta of normotensive male rats exposed to ALAN (1-2 lx) for 3 weeks. Daily, 24-h variability of pulse pressure and dP/dt(max) was observed during a regular light/dark regimen with higher values during the dark compared to the light phase of the day. ALAN suppressed 24-h variability and enhanced ultradian (<12-h) periods of pulse pressure and dP/dt(max) in duration-dependent manners. From beat-to-beat blood pressure variability, ALAN decreased low-frequency bands (a sympathetic marker) and had minimal effects on high-frequency bands. At the molecular level, ALAN decreased angiotensin II receptor type 1 expression and reduced 24-h variability. ALAN caused the appearance of 12-h oscillations in transforming growth factor β1 and fibulin 4. Expression of sarco/endoplasmic reticulum Ca2+-ATPase type 2 was increased in the middle of the light and dark phase of the day, and ALAN did not affect its daily and 12-h variability. In conclusion, ALAN suppressed 24-h variability of pulse pressure and dP/dt(max), decreased the power of low-frequency bands and differentially affected the expression of specific proteins in the rat thoracic aorta. Suppressed 24-h oscillations by ALAN underline the pulsatility of individual endocrine axes with different periods, disrupting the cardiovascular control of central blood pressure.
... In general, light activates the SCN and inhibits melatonin production. Therefore, melatonin levels are high during the dark phase of the day in both diurnal (active during the daytime) and nocturnal (active during the nighttime) animals [4,55]. The physiological consequences of ALAN are often investigated by measuring changes in melatonin levels [13,33,85]. ...
... Also, in diurnal zebra finches [54] and European blackbirds [18], a light intensity-dependent decrease in plasma melatonin was shown, whilst even < 1 lx had a significant effect. A similar decrease in plasma and pineal gland melatonin was also shown in nocturnal male Wistar rats after 2 and 5 weeks of 1-2 lx ALAN [55,65]. Interestingly, the effects of ALAN can vary depending on whether the animal is in its natural habitat or under controlled experimental conditions. ...
... In normotensive rats (18 weeks old), which exhibit nocturnal activity and are widely used as an experimental model, ALAN (5 weeks; 1-2 lx) reduced blood pressure and heart rate during the dim light phase, which led to a decrease in the daily variability of blood pressure and heart rate [55]. In spontaneously hypertensive rats (18 weeks old), which are characterised by an increased sympathetic nerve activity [47], ALAN (5 weeks; 1-2 lx) attenuated the age-related increase in blood pressure, leaving a daily heart rate variability unaffected. ...
Article
Full-text available
Artificial light at night (ALAN) affects most of the population. Through the retinohypothalamic tract, ALAN modulates the activity of the central circadian oscillator and, consequently, various physiological systems, including the cardiovascular one. We summarised the current knowledge about the effects of ALAN on the cardiovascular system in diurnal and nocturnal animals. Based on published data, ALAN reduces the day-night variability of the blood pressure and heart rate in diurnal and nocturnal animals by increasing the nocturnal values of cardiovascular variables in diurnal animals and decreasing them in nocturnal animals. The effects of ALAN on the cardiovascular system are mainly transmitted through the autonomic nervous system. ALAN is also considered a stress-inducing factor, as glucocorticoid and glucose level changes indicate. Moreover, in nocturnal rats, ALAN increases the pressure response to load. In addition, ALAN induces molecular changes in the heart and blood vessels. Changes in the cardiovascular system significantly depend on the duration of ALAN exposure. To some extent, alterations in physical activity can explain the changes observed in the cardiovascular system after ALAN exposure. Although ALAN acts differently on nocturnal and diurnal animals, we can conclude that both exhibit a weakened circadian coordination among physiological systems, which increases the risk of future cardiovascular complications and reduces the ability to anticipate stress.
... Распространение ночного уличного освещения, увеличение количества людей, работающих или отдыхающих в ночное время, а также проживание значительной части населения в условиях природного продолжительного круглосуточного освещения (КО) делает чрезвычайно актуальной проблему изучения степени опасности КО для здоровья [1,4,5]. Так, в эксперименте на грызунах выявлено негативное влияние КО на метаболические процессы (обмен глюкозы, триглицеридов, холестерина, жирных кислот) [4,13] и их гормональную регуляцию с помощью инсулина [13], глюкокортикоидов [2,9,15], мелатонина [9,15]. Гораздо меньше исследований, посвящённых изучению этих показателей у человека [4,11]. ...
... Распространение ночного уличного освещения, увеличение количества людей, работающих или отдыхающих в ночное время, а также проживание значительной части населения в условиях природного продолжительного круглосуточного освещения (КО) делает чрезвычайно актуальной проблему изучения степени опасности КО для здоровья [1,4,5]. Так, в эксперименте на грызунах выявлено негативное влияние КО на метаболические процессы (обмен глюкозы, триглицеридов, холестерина, жирных кислот) [4,13] и их гормональную регуляцию с помощью инсулина [13], глюкокортикоидов [2,9,15], мелатонина [9,15]. Гораздо меньше исследований, посвящённых изучению этих показателей у человека [4,11]. ...
... ослабленной секреции мелатонина. Действительно, в различных работах отмечалось снижение секреции мелатонина при ночном освещении [3,4,9], а также его способность модулировать секрецию глюкокортикоидов в том числе у обезьян [3,14]. ...
... Because dLAN disturbs the natural light-dark (LD) cycles, circadian clocks are considered the primary system susceptible to improper functioning, underlying the link between dLAN and increased health risks (12,13). Indeed, after chronic exposure to dLAN (≤ 5 lx), compromised circadian function has been shown experimentally through suppressed night-time melatonin levels (14,15), attenuated rhythms in locomotor activity (16) and cardiovascular parameters (14), and altered clock gene oscillations (17). Nonetheless, the underlying physiological and molecular mechanisms, how circadian disruption due to dLAN causes detrimental health effects, are still poorly understood. ...
... Because dLAN disturbs the natural light-dark (LD) cycles, circadian clocks are considered the primary system susceptible to improper functioning, underlying the link between dLAN and increased health risks (12,13). Indeed, after chronic exposure to dLAN (≤ 5 lx), compromised circadian function has been shown experimentally through suppressed night-time melatonin levels (14,15), attenuated rhythms in locomotor activity (16) and cardiovascular parameters (14), and altered clock gene oscillations (17). Nonetheless, the underlying physiological and molecular mechanisms, how circadian disruption due to dLAN causes detrimental health effects, are still poorly understood. ...
... In the current study, we tested the hypothesis that chronic exposure to low-intensity light at night (~2 lx) compromises the circadian system, leading to disturbances in the daily variation of circulating immune cells and leukocyte movement into the renal cortex under homeostatic conditions. This study follows our recently published paper, in which we demonstrated that dLAN resulted in attenuated circadian rhythms in the cardiovascular system and the suppression of nocturnal plasma melatonin levels (14), which represent an important central clock-derived output and a time-giver for peripheral oscillators (25). ...
Article
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Dim light at night (dLAN) has become a pervasive part of the modern world, and growing evidence shows its association with increased health risks. Though this link is attributed to a disturbed circadian clock, the underlying mechanisms that can explain how circadian disruption from dLAN causes negative health effects remain unclear. Here, we exposed rats to a light–dark cycle (12:12 h) with low-intensity light at night (~2 lx) for 2 and 5 weeks and explored the steady-state pattern of circulating immune cells and renal immune-related markers, which are well controlled by the circadian clock. After 5 weeks, dLAN impaired the daily variation in several types of white blood cells, especially monocytes and T cells. Two-week dLAN caused a reduction in blood monocytes and altered gene expression of macrophage marker Cd68 and monocyte-attracting chemokine Ccl2 in the kidney. Interestingly, dLAN decreased renal 3-nitrotyrosine levels and resulted in up-regulation of the main endogenous antioxidant pathways, indicating a disturbance in the renal redox balance and an activation of compensatory mechanisms. These effects paralleled the altered renal expression of the molecular clock components and increased plasma corticosterone levels. Together, our results show that chronic exposure to dLAN weakened the circadian control of daily variation of circulating immune cells and disturbed renal immune and redox homeostasis. Consequences of this dLAN-disturbed immune balance on the ability of the immune system to cope with other challenges should by clarified in further studies.
... Although the alignment of the endogenous circadian with the exogenous solar period is generally called "light entrainment", the high contrast between day and night intensity and the spectral change around dawn and dusk are necessary for the proper entrainment of the clock in nocturnal and diurnal animals [12,13]. Continuous exposure to light (LL) or even dim light at night (LAN) causes the desynchronization of SCN neurons and subsequently of the peripheral clock in bodily tissues [1,[14][15][16][17] (also see [18]). The disruption of temporal coordination throughout the body has been associated with an increased risk of cancer, immune deficiencies, metabolic syndrome, type 2 diabetes mellitus, cardiovascular disease, psychiatric diseases, and sleep diseases in human and laboratory animal models [19]. ...
... The exposure of adult nocturnal rodents to LL disrupts the circadian rhythms of locomotor activity, body temperature, and plasma melatonin level; attenuates circadian rhythms in the cardiovascular system [16,[39][40][41][42]; alters insulin secretion [41,43]; compromises the immune system [44]; and leads to anxiety and depression [45]. In this study, we determined the long-term effects of ...
... The exposure of adult nocturnal rodents to LL disrupts the circadian rhythms of locomotor activity, body temperature, and plasma melatonin level; attenuates circadian rhythms in the cardiovascular system [16,[39][40][41][42]; alters insulin secretion [41,43]; compromises the immune system [44]; and leads to anxiety and depression [45]. In this study, we determined the long-term effects of early postnatal LL conditions on the development of circadian oscillations in principal clock brain structures and activity rhythm. ...
Article
Full-text available
The circadian clock regulates bodily rhythms by time cues that result from the integration of genetically encoded endogenous rhythms with external cycles, most potently with the light/dark cycle. Chronic exposure to constant light in adulthood disrupts circadian system function and can induce behavioral and physiological arrhythmicity with potential clinical consequences. Since the developing nervous system is particularly vulnerable to experiences during the critical period, we hypothesized that early-life circadian disruption would negatively impact the development of the circadian clock and its adult function. Newborn rats were subjected to a constant light of 16 lux from the day of birth through until postnatal day 20, and then they were housed in conditions of L12 h (16 lux): D12 h (darkness). The circadian period was measured by locomotor activity rhythm at postnatal day 60, and the rhythmic expressions of clock genes and tissue-specific genes were detected in the suprachiasmatic nuclei, retinas, and pineal glands at postnatal days 30 and 90. Our data show that early postnatal exposure to constant light leads to a prolonged endogenous period of locomotor activity rhythm and affects the rhythmic gene expression in all studied brain structures later in life.
... Low ALAN levels (<10 lx) can disturb the circadian control of different physiological processes, including the cardiovascular system in men. 17 Moreover, low ALAN levels (1-2 lx) differentially affect the circadian control of BP and HR in normotensive rats 18 in comparison with spontaneously hypertensive rats, 19 which have an activated sympathetic nervous system. PH increases BP and the activity of the sympathetic nervous system, through which central biological clock outputs are mediated and can be disturbed by ALAN. ...
... We applied telemetry transmitters to the abdominal aorta. 8,18 After implantation, we treated rats with tramadol (15 mg/kg; SC; Tramal, Stada, Bad Vilbel, Germany) and placed them in a heated room. We allowed the animals to recover for 2 weeks after surgery. ...
... However, the light-dark variability of both parameters continuously decreased after 5 weeks of ALAN in PH rats, and there was no difference between the groups at that time. These results are in line with our previous study, 18 in which ALAN of the same intensity suppressed circadian variability of BP and HR in rats together with changes of spontaneous baroreflex sensitivity. On the other hand, in spontaneously hypertensive rats, 19 the consequences of ALAN resembled those in PH rats found in this study. ...
Article
Prenatal hypoxia (PH) has negative consequences on the cardiovascular system in adulthood and can affect the responses to additional insults later in life. We explored the effects of PH imposed during embryonic day 20 (10.5% O 2 for 12 h) on circadian rhythms of systolic blood pressure (BP) and heart rate (HR) in mature male rat offspring measured by telemetry. We evaluated: (1) stability of BP and HR changes after PH; (2) circadian variability of BP and HR after 2 and 5 weeks of exposure to artificial light at night (ALAN; 1–2 lx); and (3) response of BP and HR to norepinephrine. PH increased BP in the dark (134 ± 2 mmHg vs. control 127 ± 2 mmHg; p = 0.05) and marginally in the light (125 ± 1 mmHg vs. control 120 ± 2 mmHg) phase of the day but not HR. The effect of PH was highly repeatable between 21- and 27-week-old PH male offspring. Two weeks of ALAN decreased the circadian variability of HR ( p < 0.05) and BP more in control than PH rats. After 5 weeks of ALAN, the circadian variability of HR and BP were damped compared to LD and did not differ between control and PH rats ( p < 0.05). Responses of BP and HR to norepinephrine did not differ between control and PH rats. Hypoxia at the end of the embryonic period increases BP and affects the functioning of the cardiovascular system in mature male offspring. ALAN in adulthood decreased the circadian variability of cardiovascular parameters, more in control than PH rats.
... These findings are consistent with previous reports. Rats exposed to 2-5 weeks of artificial light at night (1-2 lx) resulted in suppression of plasma melatonin concentration [51], while exposure to bright light resulted in the loss of melatonin rhythms [50]. Study from our lab has shown that urban birds exhibit similar responses, and melatonin secretion is attenuated in urban birds along with altered expression of melatonin receptors [15]. ...
... Melatonin is secreted only at night, making it a useful physiological cue for nighttime [54]. Exposure to dLAN reduces nocturnal melatonin concentration [15,51] and can mislead the body's time of day information [55]. Rodents chronically exposed to dim light at night exhibit behavioral despair [56]. ...
Article
The rapid increase in urbanization is altering the natural composition of the day–night light ratio. The light/dark cycle regulates animal learning, memory, and mood swings. A study was conducted to examine the effect of different quantity and quality of light at night on the daily clock, learning, memory, cognition, and expression of transcripts in key learning centers. Treatment was similar for experiments one to three. Rats were exposed for 30 days to 12 h light and 12 h dark with a night light of 2 lx (dLAN group), 250 lx (LL), or without night light (LD). In experiment one, after 28 days, blood samples were collected and 2 days later, animals were exposed to constant darkness. In experiment two, after 30 days of treatment, animals were subjected to various tests involving learning, memory, and cognition. In experiment three, after 30 days of treatment, animals were sampled, and transcript levels of brain-derived neurotrophic factor, tyrosine kinase, Growth-Associated Protein 43, Neurogranin, microRNA-132, cAMP Response Element-Binding Protein, Glycogen synthase kinase-3β, and Tumor necrosis factor α were measured in hippocampus, thalamus, and cortex tissues. In experiment four, animals were exposed to night light of 0.019 W/m2 but of either red (640 nm), green (540 nm), or blue (450 nm) wavelength for 30 days, and similar tests were performed as mentioned in experiment 2. While in experiment five, after 30 days of respective wavelength treatments, all animals were sampled for gene expression studies. Our results show that exposure to dLAN and LL affects the daily clock as reflected by altered melatonin secretion and locomotor activity, compromises the learning, memory, and cognitive ability, and alterations in the expression levels of transcripts in the hypothalamus, cortex, and thalamus. The effect is night light intensity dependent. Further, blue light at night has less drastic effects than green and red light. These results could be of the potential use of framing the policies for the use of light at night.Graphical abstract
... Therefore, both these routes may be implicated in ALAN effects on the timing of the corticosterone rhythm. Consistent with this view, in our previous study, we demonstrated an enhanced cardiovascular response to norepinephrine in rats under ALAN regime [47], suggesting effects on the autonomic regulation and altered sensitivity of ALANexposed animals to stressors. ...
... Another key output controlled by the central clock is MEL, which exhibits a clear daily rhythm with higher levels during the dark phase than during the light phase, thereby transmitting circadian information to different organs and tissues in the body, including the brain [48]. Consistent with our previous findings [47] and with other published reports in rats [15,49], we found that low levels of nocturnal light fully eliminated the MEL oscillations in the circulation. The MEL rhythm is considered a reliable measure of central clock functioning, which may act as a timing signal to adjust the profile and phase of other hormonal rhythms, such as corticosterone and leptin [50]. ...
Article
Aims: Our study addresses underlying mechanisms of disruption of the circadian timing system by low-intensity artificial light at night (ALAN), which is a growing global problem, associated with serious health consequences. Methods: Rats were exposed to low-intensity (~2 lx) ALAN for 2 weeks. Using in situ hybridization, we assessed 24-h profiles of clock and clock-controlled genes in the suprachiasmatic nuclei (SCN) and other hypothalamic regions, which receive input from the master clock. Moreover, we measured daily rhythms of hormones within the main neuroendocrine axes as well as the detailed daily pattern of feeding and drinking behavior in metabolic cages. Results: ALAN strongly suppressed the molecular clockwork in the SCN, as indicated by the suppressed rhythmicity in the clock (Per1, Per2 and Nr1d1) and clock output (arginine vasopressin) genes. ALAN disturbed rhythmic Per1 expression in the paraventricular and dorsomedial hypothalamic nuclei, which convey the circadian signals from the master clock to endocrine and behavioral rhythms. Disruption of hormonal output pathways was manifested by the suppressed and phase-advanced corticosterone rhythm and lost daily variations in plasma melatonin, testosterone, and vasopressin. Importantly, ALAN altered the daily profile in food and water intake and eliminated the clock-controlled surge of drinking two hours prior to the onset of the rest period, indicating disturbed circadian control of anticipatory thirst and fluid balance during sleep. Conclusion: Our findings highlight compromised time-keeping function of the central clock and multiple circadian outputs, through which ALAN disturbs the temporal organization of physiology and behavior.
... e CCT and CRI of the light source are determined by the spectral content at different wavelengths. In the experiment, seven kinds of CCT are selected, which are 3000 K, 3500 K, 4000 K, 4500 K, 5000 K, 5700 K, and 6500 K. Our previous research shows that CRI2012 has a good evaluation effect on tunnel lighting environment from several current color rendering evaluation indexes [21]. erefore, this paper uses CRI2012 to study the CRI of tunnel led. ...
... ere are four main C (λ) models: Brainard model based on melatonin inhibition, apan model based on melatonin inhibition, Jiaqi Ju model based on heart rate change, and Berman model based on pupil size change [22,[28][29][30]. Recent studies have shown that the nonvisual biological effect is mainly caused by the action of ipRGCs, which can transmit the induced light signal to the supraoptic nucleus and then control the secretion of melatonin in pineal gland [21,[31][32][33][34]. Melatonin can increase fatigue and accelerate the state of sleepiness, which leads to poor reaction ability and judgment ability and affects automatic function [35]. ...
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Judicious use of lamps is of profound significance to improve the internal traffic safety of tunnels. This study evaluated the biological effects of spectrum on human visual and nonvisual under mesopic vision category. According to the difference of human eyes’ response to the visual and nonvisual biological effects of different wavelengths of light radiation, a method of applying the mesopic visual spectral luminous efficiency curve to the assessment of nonvisual biological effects and blue light hazards is proposed. The results show that, in theory, under mesopic vision category, the spectrum with high correlation color temperature (CCT) and high color rendering index (CRI) has higher blue light content Z-value and has greater impact on human nonvisual effects and blue light radiation damage, but it can also provide higher human perception luminance. The visual effect detection experiment of driving in the interior zones of the tunnel is simulated in the laboratory, and the critical flicker frequency and reaction time are taken as physiological indexes. The results show that the spectrum with high CCT and high CRI corresponds to lower critical flicker frequency drop value and faster reaction time, which has a positive effect on improving driving safety. Therefore, this paper suggests that the LED with high CCT and high CRI (CCT = 6500 K, CRI2012 = 95) should be used in the interior zones of the tunnel with relatively short lighting section, and the CCT and CRI should be appropriately reduced in other road environments with long lighting section to reduce the impact of spectrum on nonvisual photobiology, so as to improve road traffic safety.
... Several other experiments observing activity of Wistar rats, when exposed to light, corroborated this finding (Molcan, et al., 2019;Opperhuizen, et al., 2017;Zeman, et al., 2016). ...
Article
Highveld mole-rats (Cryptomys hottentotus pretoriae) are social rodents that inhabit networks of subterranean tunnels. In their natural environment, they are rarely exposed to light, and consequently their visual systems have regressed over evolutionary time. However in the laboratory they display nocturnal activity suggesting that they are sensitive to changes in ambient illumination. We examined the robustness of the highveld mole-rat circadian system by assessing its locomotor activity under decreasing light intensities. Mole-rats were subjected to seven consecutive light cycles commencing with a control cycle (overhead fluorescent lighting at 150 lux), followed by decreasing LED lighting (500, 300, 100, 10, and 1 lux) on a 12L:12D photoperiod and finally a constant darkness (DD) cycle. Mole-rats displayed nocturnal activity under the whole range of experimental lighting conditions, with a distinct spike in activity at the end of the dark phase in all cycles. The mole-rats were least active during the control cycle under fluorescent light, locomotor activity increased steadily with decreasing LED light intensities, and the highest activity was exhibited when the light was completely removed. In constant darkness, mole-rats displayed free-running rhythms with periods (tau) ranging from 23.77 – 24.38 h, but was overall very close to 24h at 24.07 h. Our findings confirm that the highveld mole-rat has a higher threshold for light compared to aboveground dwelling rodents, which is congruent with previous neurological findings, and has implications for behavioural rhythms.
... The actuator will regulate the amount of voltage used in the room lights. So that 3 zones of room lights can be lit according to a predetermined room lighting standard of 300 lux [22]- [24]. Figures 3 and 4 shows the measurement block diagram of lamp automation. ...
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Lamp automation is utilized to adjust the lighting in the classroom by adjusting to the level of sunlight intensity outside the classroom. The light intensity will be adjusted to the utilization of lights as indicated by the need to enlighten a room. Therefore, this research aims to depict the design of a light intensity measurement system using a BH1750 sensor that will be carried out to measure the intensity of sunlight in units of light (lux). The signal from the sensor will be transmitted to a mini pc which functions to process measurement data and display it on the graphical user interface (GUI). As a result, the sensor will instruct the dimmer as an actuator to control the classroom lights according to the lighting from the sun. This system is already installed in the classroom and can save energy around 35 kWh a year.
... If changes occur in external light/dark environmental signals, cardiovascular dysfunction may result. Molcan et al. (2019) found that under the condition of 12-12 h LD, 1-2 Lux ALAN exposure for 5 weeks reduced the diurnal expression amplitude of hemodynamic parameters and the secretion of melatonin in Wistar rats. The researchers proposed that ALAN attenuated circadian control of the cardiovascular system, imposing negative consequences on cardiovascular health. ...
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Artificial light at night (ALAN) pollution has been regarded as a global environmental concern. More than 80% of the global population is exposed to light pollution. Exacerbating this issue, artificially lit outdoor areas are growing by 2.2% per year, while continuously lit areas have brightened by 2.2% each year due to rapid population growth and expanding urbanization. Furthermore, the increasing prevalence of night shift work and smart device usage contributes to the inescapable influence of ALAN. Studies have shown that ALAN can disrupt endogenous biological clocks, resulting in a disturbance of the circadian rhythm, which ultimately affects various physiological functions. Up until now, scholars have studied various disease mechanisms caused by ALAN that may be related to the response of the circadian system to light. This review outlines the molecular mechanisms by which ALAN causes circadian rhythm abnormalities in sleep disorders, endocrine diseases, cardiovascular disease, cancer, immune impairment, depression, anxiety and cognitive impairments.
... Notably, the C57BL/6J strain, like many common inbred strains, does not produce melatonin (Roseboom et al., 1998;Kennaway, 2019) while there is evidence that the outbred Smith Webster strain does (Estrada-Reyes et al., 2018). Melatonin, along with glucocorticoids, is a primary endocrine clock output and is involved in synchronizing peripheral rhythms (Kennaway and Wright, 2002;Meléndez-Fernández et al., 2023) and dLAN reduces nocturnal melatonin secretion in rats (Molcan et al., 2019;Rumanova et al., 2020). Although melatonin has diverse and complex interactions depending on the specific physiological and experimental context, it seems to largely have an anti-inflammatory effect on microglia (Hardeland, 2018(Hardeland, , 2021, suggesting that it would have a neuroprotective role in CNS injury models. ...
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Spinal cord injury (SCI) can cause long-lasting locomotor deficits, pain, and mood disorders. Anatomical and functional outcomes are exacerbated by inflammation after SCI, which causes secondary damage. One promising target after SCI is manipulating the circadian system, which optimizes biology and behavior for time of day – including neuroimmune responses and mood-related behaviors. Circadian disruption after SCI is likely worsened by a disruptive hospital environment, which typically includes dim light-at-night (dLAN). Here, we hypothesized that mice subjected to SCI, then placed in dLAN, would exhibit worsened locomotor deficits, pain-like behavior, and anxiety-depressive-like symptoms compared to mice maintained in light days with dark nights (LD). C57BL6/J mice received sham surgery or moderate T9 contusion SCI, then were placed permanently in LD or dLAN. dLAN after SCI did not worsen locomotor deficits; rather, SCI-dLAN mice showed slight improvement in open-field locomotion at the final timepoint. Although dLAN did not alter SCI-induced heat hyperalgesia, SCI-dLAN mice exhibited worsened mechanical allodynia at 13 days post-SCI compared to SCI-LD mice. SCI-LD and SCI-dLAN mice had similar outcomes using sucrose preference (depressive-like) and open-field (anxiety-like) tests. At 21 dpo, SCI-dLAN mice had reduced preference for a novel juvenile compared to SCI-LD, implying that dLAN combined with SCI may worsen this mood-related behavior. Finally, lesion size was similar between SCI-LD and SCI-dLAN mice. Therefore, newly placing C57BL6/J mice in dLAN after SCI had modest effects on locomotor, pain-like, and mood-related behaviors. Future studies should consider whether clinically-relevant circadian disruptors, alone or in combination, could be ameliorated to enhance outcomes after SCI.
... Melatonin exhibits an approximate 24-hour rhythm with peak secretion during the dark phase that persists even in the absence of external time cues [4][5][6]. Thus, circulating melatonin may bring a measure of the damage caused by light into the human body [7][8][9][10][11][12][13]. The blue region of the spectrum maximally stimulates melanopsin present in intrinsically photosensitive retinal ganglion cells (ipRGCs) that convey light information to the central nervous system and among other processes, leads to melatonin suppression [1]. ...
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This review presents the main metrics developed so far to correlate physical properties of light and its effects on melatonin suppression. Melatonin is a hormone secreted at night and its production is suppressed by exposure to light. In this context, the negative effects of lighting at night and high exposure to light raise the need for a better quantification of these impacts on health. Different light action spectroscopy methodologies have been recently used to characterize the circadian response mediated by melatonin in humans, but there is so far no consensus on a main validated model. While complementary studies are still necessary to reach such an ideal model, here we analyze and compare the results of works that developed and tested metrics based on the absorption curves of human melanopsin, rods and cones, and on the dynamics of melatonin suppression in different light regimes. These studies reveal how the spectral composition, irradiance and temporality of light modulate the function of human melatonin. We present milestones in this research field, together with discussion on the advances, limitations and perspectives of application for distinct available models. Applied to different contexts, this knowledge can bring favorable changes to health in environmental lighting projects, production of ophthalmic lenses, screens, filters, films, and other optical devices.
... Numerous human and animal experiments have demonstrated that ALAN disrupts circadian rhythms and suppresses melatonin secretion at night (Blask et al. 2005;Chang et al. 2015;Molcan et al. 2019;Sugden 1989;Touitou et al. 2017;Wehr 1991). Our experiments set the same illumination of 1000 lx among three groups from 19:00 and 22:00 at night. ...
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Abstract The desynchronization of circadian rhythms affected by light may induce physiological and psychological disequilibrium. We aimed to elucidate changes of growth, depression-anxiety like behaviors, melatonin and corticosterone (CORT) secretion, and gut microbiota in rats influenced by long-term light inputs. Thirty male Sprague–Dawley rats were exposed to a 16/8 h light/dark regime for 8 weeks. The light period was set to 13 h of daylight with artificial light (AL group, n = 10), or with natural light (NL group, n = 10), or with mixed artificial-natural light (ANL group, n = 10), and 3 h of artificial night light after sunset. The obtained findings indicated that the highest weight gain and food efficiency were observed in the AL group and the lowest in NL group. In the behavioral tests, the NL and ANL groups showed lower anxiety level than AL group, and ANL groups showed lower depression level than AL group. The NL and ANL groups had delayed acrophases and maintained higher concentrations of melatonin compared to AL group. The circadian rhythm of CORT was only found in ANL group. At the phylum level, the mixed light contributed to a lower abundance of Bacteroidetes. The genus level results recommend a synergistic effect of artificial light and natural light on Lactobacillus abundance and an antagonistic effect on the Lachnospiraceae_NK4A136_group abundance. The study indicated that the mixture of artificial and natural light as well as the alignment of the proportions had beneficial influences on depression-anxiety-like levels, melatonin and corticosterone secretion, and the composition of the gut microbiota. Key points • The mixed light can reduce the depression-anxiety level • The mixed light can maintain the secretion rhythm of melatonin and CORT • The mixed light can increase Lactobacillus and decrease Lachnospiraceae_NK4A136_group
... [60,61] Here we found that 5 weeks of DLAN decreased nighttime melatonin plasmatic levels, this agrees with previous studies that reported suppression of melatonin secretion in DLAN male rats exposed for 2 and 5 weeks. [62,63] Another important hormone whose secretion is regulated by the SCN is corticosterone. The SCN regulates corticosterone secretion through the hypothalamus-pituitary-adrenal axis. ...
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Inhabitants of urban areas are constantly exposed to light at night, which is an important environmental factor leading to circadian disruption. Streetlights filtering light through the windows and night dim light lamps are common sources of dim light at night (DLAN). The female population is susceptible to circadian disruption. The present study is aimed to determine the impact of DLAN on female Wistar rats circadian rhythms, metabolism, reproductive physiology, and behavior. After 5 weeks of DLAN exposure daily, oscillations in activity and body temperature of female rats are abolished. DLAN also decreases nocturnal food ingestion, which results in a diminishment in total food consumption. These alterations in the temporal organization of the body are associated with a significant decrease in melatonin plasmatic levels, reproductive disruptions, decreased exploration times, and marked anhedonia. This study highlights the importance of avoiding exposure to light at night, even at low intensities, to maintain the circadian organization of physiology, and denotes the great necessity of increasing the studies in females since the sexual dimorphism within the effects of desynchronizing protocols has been poorly studied.
... The stimulus for melatonin synthesis and secretion is darkness, and light inhibits its production. Thus, artificial light production at night leads to a shift in melatonin production with potential health disturbances from chronodisruption [113,142]. ...
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Anxiety disorders are the most common mental diseases. Anxiety and the associated physical symptoms may disturb social and occupational life and increase the risk of somatic diseases. The pathophysiology of anxiety development is complex and involves alterations in stress hormone production, neurosignaling pathways or free radical production. The various manifestations of anxiety, its complex pathophysiological background and the side effects of available treatments underlie the quest for constantly seeking therapies for these conditions. Melatonin, an indolamine produced in the pineal gland and released into the blood on a nightly basis, has been demonstrated to exert anxiolytic action in animal experiments and different clinical conditions. This hormone influences a number of physiological actions either via specific melatonin receptors or by receptor-independent pleiotropic effects. The underlying pathomechanism of melatonin’s benefit in anxiety may reside in its sympatholytic action, interaction with the renin–angiotensin and glucocorticoid systems, modulation of interneuronal signaling and its extraordinary antioxidant and radical scavenging nature. Of importance, the concentration of this indolamine is significantly higher in cerebrospinal fluid than in the blood. Thus, ensuring sufficient melatonin production by reducing light pollution, which suppresses melatonin levels, may represent an endogenous neuroprotective and anxiolytic treatment. Since melatonin is freely available, economically undemanding and has limited side effects, it may be considered an additional or alternative treatment for various conditions associated with anxiety.
... The differences in plasma melatonin concentrations in P3 pups between both groups probably reflect the suppression of melatonin in pregnant ALAN mothers because, at this age, the pineal gland does not synthesize melatonin rhythmically [36]. Although we did not measure the melatonin levels in pregnant female rats in this study to avoid an additional stress stimulus, our previous studies convincingly showed that the night-time illuminance applied in this experiment suppressed plasma melatonin rhythm in adult male rats [35,37]. In previous studies, higher levels of ALAN were applied to explore the effect of ALAN, from 5 lx [13,15] to 20 lx [38]. ...
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Artificial light at night (ALAN) is considered an environmental risk factor that can interfere with the circadian control of the endocrine system and metabolism. We studied the impact of ALAN during pregnancy on the hormonal and biochemical parameters in rat pups at postnatal (P) days P3, P10, and P20. Control dams (CTRL) were kept in a standard light-dark regime, and ALAN dams were exposed to dim ALAN (<2 lx) during the whole pregnancy. A plasma melatonin rhythm was found in all CTRL groups, whereas in ALAN pups, melatonin was not rhythmic at P3, and its amplitude was lowered at P10; no differences were found between groups at P20. Plasma corticosterone was rhythmic at P20 in both groups, with decreased mesor in ALAN pups. Plasma thyroid hormones exhibited an inconsistent developmental pattern, and vasopressin levels were suppressed at the beginning of the dark phase at P20 in ALAN compared to CTRL. Glucose and cholesterol showed significant daily rhythms in CTRL but not in ALAN offspring at P3. Exposure to ALAN during pregnancy disturbed the development of daily rhythms in measured hormones and metabolites, suggesting that ALAN during pregnancy can act as an endocrine disruptor that can interfere with the normal development of the progeny.
... In peripheral tissues, clock gene rhythms appeared to be less affected by ALAN than in the master oscillator, though they showed lowered amplitude or shifts in acrophase [127,129,131]. The daily plasma melatonin rhythm was eliminated in rats after 2 weeks of dim ALAN (2 lx) exposure due to suppressed nocturnal melatonin levels [129], which were also reported in other studies, not only in rats [133,134] but also in diurnal birds [135,136] and humans [137]. Moreover, circadian disruption induced by dim ALAN has been observed in other hormonal rhythms, e.g., suppressed and phase-advanced corticosterone rhythm, and abolished daily rhythmicity in plasma testosterone and vasopressin levels in rats [129]. ...
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Circadian rhythms control almost all aspects of physiology and behavior, allowing temporal synchrony of these processes between each other, as well as with the external environment. In the immune system, daily rhythms of leukocyte functions can determine the strength of the immune response, thereby regulating the efficiency of defense mechanisms to cope with infections or tissue injury. The natural light/dark cycle is the prominent synchronizing agent perceived by the circadian clock, but this role of light is highly compromised by irregular working schedules and unintentional exposure to artificial light at night (ALAN). The primary concern is disrupted circadian control of important physiological processes, underlying potential links to adverse health effects. Here, we first discuss the immune consequences of genetic circadian disruption induced by mutation or deletion of specific clock genes. Next, we evaluate experimental research into the effects of disruptive light/dark regimes, particularly light-phase shifts, dim ALAN, and constant light on the innate immune mechanisms under steady state and acute inflammation, and in the pathogenesis of common lifestyle diseases. We suggest that a better understanding of the mechanisms by which circadian disruption influences immune status can be of importance in the search for strategies to minimize the negative consequences of chronodisruption on health.
... Exposure to ALAN may inhibit melatonin production in the pineal gland, as has been demonstrated in hamsters and rats(Dauchy et al., 2010;Dauchy et al., 2015;Evans et al., 2007;Molcan et al., 2019). In this process, PPARα may played a mediating role in alan-induced adaptive metabolism and lipid deposition in the adipose tissue(Luo et al., 2020). ...
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Background Previous studies have shown that artificial light at night (ALAN) is associated with obesity in adults or school-aged children, however, without addressing the critical transition period from adolescence to young adulthood. Methods In this study, we recruited incoming students from five geographically dispersed universities across China whose mean ALAN (nanowatts/cm²/sec) during adolescence was obtained using remotely observed nighttime data matched with information on their residence. Body weight and height were measured in a field survey. A mixed generalized linear model assessed the association between ALAN levels and body mass index (BMI). Results A total of 19,344 participants were included with a mean age and BMI of 18.3 ± 0.7 years and 21.2 ± 3.0 kg/m², respectively. Our findings indicated a significant association between ALAN levels during the past 6 years and BMI (β = 0.1, 95% CI: 0.06–0.14, p < 0.0001). The results remained robust after multiple sensitivity analyses and adjustment for age, sex, parental educational, smoking, alcohol, and physical activity. In addition, a significant association between ALAN levels and BMI was observed in males (β = 0.23, 95% CI: 0.17–0.29, p < 0.0001) but not in females (β = 0.03, 95% CI: to0.08-0.02, p = 0.24). Conclusion These results reveal for the first time that ALAN exposure during adolescence is associated with subsequent increases in BMI at young adulthood. Further studies could help elucidate this association and clarify whether reducing exposure to ALAN during adolescence could contribute to obesity prevention in young adults.
... Disruption of circadian rhythms by environmental conditions can lead to changes in body homeostasis, from behavior to body metabolism. The circadian system maintains internal 24 h behavioral and physiological fluctuations whose inconsistency with the external light-dark (LD) cycle can lead to negative health outcomes [52], of which the light-dark cycle is the most reliable environment factor [55]. Melatonin and corticosterone, the two most recognized circadian output hormones, exhibit marked circadian rhythm [56]. ...
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Light pollution is one of the most serious public problems, especially the night light. However, the effect of dim blue light at night (dLAN-BL) on cognitive function is unclear. In this study, we evaluated the effects of exposure to dLAN-BL in C57BL/6J mice for 4 consecutive weeks. Our results showed dLAN-BL significantly impaired spatial learning and memory and increased plasma corticosterone level in mice. Consistent with these changes, we observed dLAN-BL significantly increased the numbers and activation of microglia and the levels of oxidative stress product MDA in the hippocampus, decreased the levels of antioxidant enzymes Glutathione peroxidase (GSH-Px), Superoxide dismutase (SOD), Gluathione reductase (Gsr), total antioxidants (T-AOC) and the number of neurons in the hippocampus, up-regulated the mRNA expression levels of IL6, TNF-α and the protein expression levels of iNOS, COX2, TLR4, p-p65, Cleaved-Caspase3 and BAX, and down-regulated the mRNA expression levels of IL4, IL10, Psd95, Snap25, Sirt1, Dcx and the protein expression level of BCL2. In vitro results further showed corticosterone (10uM)-induced BV2 cell activation and up-regulated content of IL6, TNF-α in the cell supernatant and the protein expression levels of iNOS, COX2, p-p65 in BV2 cells. Our findings suggested dLAN-BL up-regulated plasma corticosterone level and hippocampal microglia activation, which in turn caused oxidative stress and neuroinflammation, leading to neuronal loss and synaptic dysfunction, ultimately leading to spatial learning and memory dysfunction in mice.
... Most vertebrates, including humans, lose the ability to discriminate color at moonlight intensities (∼0.01 cd m 2 ; , and so responses to dim light at night may be primarily non-visual. Indeed, effects of ALAN at very dim levels (0.1-2 lux) on sleep, circadian rhythms, and cardiovascular physiology are thought to be mediated by stimulation of non-visual photoreceptors and consequent suppression of nighttime melatonin (Evans et al. 2007;Dominoni et al. 2013;Obayashi et al. 2014;Alaasam et al. 2018Alaasam et al. , 2021Spoelstra et al. 2018;Molcan et al. 2019;Rumanova et al. 2019). However, exceptions exist such as helmethead geckos (Tarentola chazaliae) which have no rod photoreceptors and maintain color discrimination at even moonlight intensities (0.002 cd m 2 ; Roth and Kelber 2004;Kelber and Lind 2010). ...
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Synopsis Artificial light at night (ALAN) is a pervasive anthropogenic pollutant, emanating from urban and suburban developments and reaching nearly all ecosystems from dense forests to coastlines. One proposed strategy for attenuating the consequences of ALAN is to modify its spectral composition to forms that are less disruptive for photosensory systems. However, ALAN is a complicated pollutant to manage due to the extensive variation in photosensory mechanisms and the diverse ways these mechanisms manifest in biological and ecological contexts. Here, we highlight the diversity in photosensitivity across taxa and the implications of this diversity in predicting biological responses to different forms of night lighting. We curated this paper to be broadly accessible and inform current decisions about the spectrum of electric lights used outdoors. We advocate that efforts to mitigate light pollution should consider the unique ways species perceive ALAN, as well as how diverse responses to ALAN scale up to produce diverse ecological outcomes.
... The reason for this is that in our society, almost everyone is at risk of being out of sync due to modern infrastructure (i.e., artificial light, social media, irregular sleep-wake schedules, time zone changes, etc.). As an example, analysis of human circadian transcriptomes from biopsy samples suggests that approximately 20% of the population is significantly lagged relative to most, perhaps reflecting the prevalence of shift work in developed countries, also the effect of light, its intensity, color and timing, as well as behavioral activity, are important as inputs to the clock (Anafi et al., 2017;Lucassen et al., 1995;van Oosterhout et al., 2012;Opperhuizen et al., 2017;Itzhacki et al., 2018;Molcan et al., 2019;Nagai et al., 2019;Phillips et al., 2019). ...
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The objective of chronotherapy is to optimize medical treatments taking into account the body's circadian rhythms. Chronotherapy is referred to and practiced in two different ways: (1) to alter the sleep-wake rhythms of patients to improve the sequels of several pathologies; (2) to take into account the circadian rhythms of patients to improve therapeutics. Even minor dysfunction of the biological clock can greatly affect sleep/wake physiology causing excessive diurnal somnolence, increase in sleep onset latency, phase delays or advances in sleep onset, frequent night awakenings, reduced sleep efficiency, delayed and shortened rapid eye movement sleep, or increased periodic leg movements. Chronotherapy aims to restore the proper circadian pattern of the sleep-wake cycle, through adequate sleep hygiene, timed light exposure, and the use of chronobiotic medications, such as melatonin, that affect the output phase of circadian rhythms, thus controlling the clock. Concerning the second use of chronotherapy, therapeutic outcomes as diverse as the survival after open-heart surgery or the efficacy and tolerance to chemotherapy vary according to the time of day. However, humans are heterogeneous concerning the timing of their internal clocks. Not only different chronotypes exist but also the endogenous human circadian period (τ) is not a stable trait as it depends on many internal and external factors. If any scheduled therapeutic intervention is going to be optimized, a tool is needed for simple diagnostic and objectively measurement of an individual's internal time at any given time. Methodologic advances like the use of single-sample gene expression and metabolomics are discussed.
... Both endothelial nitric oxide synthase and NADPH oxidases (Nox), two factors involved in producing vasodilators (EDRF, EDHF, and PGI2) exhibit circadian variations in vasculature (Denniff et al., 2014). In addition to this time of day variation, disruption of circadian rhythms from exposure to dim light at night (dLAN; 1-2 lux) resulted in increased NOS3 protein expression in the arteries after 2 weeks of exposure in male Wistar rats (Molcan et al., 2019). Furthermore, NOS3 knockout mice display increased infarct sizes compared to wild type mice post middle cerebral artery occlusion (MCAO) (Huang et al., 1996). ...
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Several endogenous and exogenous factors interact to influence stroke occurrence, in turn contributing to discernable daily distribution patterns in the frequency and severity of cerebrovascular events. Specifically, strokes that occur during the morning tend to be more severe and are associated with elevated diastolic blood pressure, increased hospital stay, and worse outcomes, including mortality, compared to strokes that occur later in the day. Furthermore, disrupted circadian rhythms are linked to higher risk for stroke and play a role in stroke outcome. In this review, we discuss the interrelation among core clock genes and several factors contributing to ischemic outcomes, sources of disrupted circadian rhythms, the implications of disrupted circadian rhythms in foundational stroke scientific literature, followed by a review of clinical implications. In addition to highlighting the distinct daily pattern of onset, several aspects of physiology including immune response, endothelial/vascular and blood brain barrier function, and fibrinolysis are under circadian clock regulation; disrupted core clock gene expression patterns can adversely affect these physiological processes, leading to a prothrombotic state. Lastly, we discuss how the timing of ischemic onset increases morning resistance to thrombolytic therapy and the risk of hemorrhagic transformation.
... A consistent light-dark cycle can entrain circadian rhythms, while even brief interruptions, especially the dark period, can reset the clock (Kennaway, 2005). In vertebrates, exposure to dim light at night (~1 lux) affects clock gene expression and metabolism Molcan et al., 2019). The same levels are sufficient to interrupt the behavioral and physiological processes of immature black field crickets and fruit flies (McLay et al., 2018). ...
Article
Artificial light at night (ALAN) is a major driver of firefly population declines, but its physiological effects are not well understood. To investigate the impact of ALAN on firefly development, we exposed larval Aquatica ficta fireflies to ALAN for two weeks. High larval mortality was observed in the periods of 1 to 68 days and 106 to 134 days post-treatment, which may represent the short- and long-term impacts of ALAN. We then profiled the transcriptome of larval Aquatica ficta fireflies following two weeks of ALAN exposure. A total of 1262 (1.67% out of 75777 unigenes) were differentially expressed in the treatment group: 1157 were down-regulated, and 105 were up-regulated. Up-regulated unigenes were related to regulation of hormone levels, ecdysteroid metabolic process, and response to stimulus; down-regulated unigenes were related to negative regulation of insulin receptor signaling, germ cell development, oogenesis, spermatid development, and regulation of neuron differentiation. Transcriptome results suggest that the endocrine, reproductive, and neural development of firefly larvae could be impaired by even relatively brief period of ALAN exposure. This report contributes a much-needed molecular perspective to the growing body of research documenting the fitness impacts of ALAN on bioluminescent fireflies.
... Similar to LL conditions, dLAN reduced nocturnal melatonin levels in rats [56,68,69]. The melatonin biosynthesis is highly sensitive to nocturnal light exposure, and even the illumination of 0.2 lx efficiently suppressed its high night-time concentration [56]. ...
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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.
... Smart cities of a past paradigm, and not smarter that take full advantage of big data analytics, can only be "panaceas for solving the kind of wicked and intractable problems that characterize the urban domain" [1] accompanied by novel applications and services [6,7]. Urban lighting is a major source of energy consumption [8] and affects biodiversity [9,10], scientific research through light pollution [11], human well-being as well as health [12,13]. As such, urban lighting is a major player in all the factors that determine urban sustainability. ...
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The scope of the present paper is to promote social, cultural and environmental sustainability in cities by establishing a conceptual framework and the relationship amongst safety in urban public space (UPS), lighting and Information and Communication Technology (ICT)-based surveillance. This framework uses available technologies and tools, as these can be found in urban equipment such as lighting posts, to enhance security and safety in UPS, ensuring protection against attempted criminal activity. Through detailed literary research, publications on security and safety concerning crime and lighting can be divided into two periods, the first one pre-1994, and the second one from 2004–2008. Since then, a significant reduction in the number of publications dealing with lighting and crime is observed, while at the same time, the urban nightscape has been reshaped with the immersion of light-emitting diode (LED) technologies. Especially in the last decade, where most municipalities in the EU28 (European Union of all the member states from the accession of Croatia in 2013 to the withdrawal of the United Kingdom in 2020) are refurbishing their road lighting with LED technology and the consideration of smart networks and surveillance is under development, the use of lighting to deter possible attempted felonies in UPS is not addressed. To capitalize on the potential of lighting as a deterrent, this paper proposes a framework that uses existing technology, namely, dimmable LED light sources, presence sensors, security cameras, as well as emerging techniques such as artificial intelligence (AI)-enabled image recognition algorithms and big data analytics and presents a possible system that could be developed as a stand-alone product to alert possible dangerous situations, deter criminal activity and promote the perception of safety thus linking lighting and ICT-based surveillance towards safety and security in UPS.
... The amplitude of the rhythm was dampened, with peak temperature being decreased and occurring 3 hours earlier (49). Nocturnal melatonin levels were shown to be suppressed by dLAN in rats (41,53). ...
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Lately, the incidence of overweight, obesity, and type 2 diabetes has shown a staggering increase. To prevent and treat these conditions, one must look at their etiology. As life on earth has evolved under the conditions of nature’s 24‐hour light/dark cycle, it seems likely that exposure to artificial light at night (LAN) would affect physiology. Indeed, ample evidence has shown that LAN impacts many metabolic parameters, at least partly via the biological clock in the suprachiasmatic nucleus of the hypothalamus. This review focuses on the impact of chronic and acute effects of LAN of different wavelengths on locomotor activity, food intake, the sleep/wake cycle, body temperature, melatonin, glucocorticoids, and glucose and lipid metabolism. While chronic LAN disturbs daily rhythms in these parameters, experiments using short‐term LAN exposure also have shown acute negative effects in metabolically active peripheral tissues. Experiments using LAN of different wavelengths not only have indicated an important role for melanopsin, the photopigment found in intrinsically photosensitive retinal ganglion cells, but also provided evidence that each wavelength may have a specific impact on energy metabolism. Importantly, exposure to LAN has been shown to impact glucose homeostasis also in humans and to be associated with an increased incidence of overweight, obesity, and atherosclerosis.
... Similar to all other systems in the body, the cardiovascular system is controlled by the pineal gland. Its activity changes depending on the phase of the circadian cycle (light/darkness), as suggested by fluctuations in blood pressure and heart rhythm variability [5,8]. However, the effects of melatonin synthesised by the pineal gland vary in males and females that is associated not only with the ability of this hormone to regulate the synthesis of sex hormones [4,9,10], but also to its capability to change the activity of sympathetic and parasympathetic components of the autonomic nervous system (ANS) [11,12]. ...
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Background. Cardiovascular disease is the main cause of morbidity predominantly in males. Stress is one of the crucial factors, especially with light desynchronosis. Objective of the study was to assess gender-specific characteristics of cardiac vegetative control in myocardial necrosis in cases of light deprivation. Methods. Cardiac vegetative control in adrenaline-induced myocardial necrosis (AIMN) in a setting of light deprivation (LD) was assessed in 72 mature white rats of both sexes. The animals were divided into 2 groups: G1 – the animals kept under day/night cyclic balance (12 hours/12 hours); G2 – the animals kept at LD (illumination 0.5-1 LX) for 10 days. On Day 11, AIMN caused by adrenaline (0.5 mg/kg) and heart rate variability (HRV) was assessed in 1 hour and 24 hours. Results. The development of AIMN at LD in the ♂G2 led to HRV increase that was caused by augmentation of parasympathetic and reduction of sympathetic cardiac effects. In cases of AIMN, changes of CVC in the ♀G2 were similar to the ♀G1. However, in 1 hour of AIMN, parasympathetic cardiac effects were more significant than in the ♀G1. While the ♀G2 AIMN animals experienced balanced sympathetic and parasympathetic actions, the predominance of the sympathetic component was evidenced in the ♀G1 AIMN animals. Conclusions. Light deprivation has different effects on baseline sympathetic/parasympathetic balance in males and females, i.e. increased parasympathetic control of heart rhythm in males and maintenance of sympathetic/ parasympathetic balance in females.
... Similar to LL conditions, dLAN reduced nocturnal melatonin levels in rats [56,68,69]. The melatonin biosynthesis is highly sensitive to nocturnal light exposure, and even the illumination of 0.2 lx efficiently suppressed its high night-time concentration [56]. ...
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Background. The medico-social significance of functional gastrointestinal disorders (FGID) in children is due to their prevalence and impact on the quality of life of patients. According to the biopsychosocial model, FGID are heterogeneous diseases that arise as a result of a complex interaction of biological, psychoemotional, and psychosocial factors. Objective: based on the gene­ralization of available literature data, to highlight the influence of serotonin and melatonin neurotransmitters on the course of FGIR associated with emotional volitional disturbances caused by stress in children. Materials and methods. Modern domestic and international scientific literature on the influence of serotonin and melatonin on the course of FGIR associated with emotional volitional disturbances caused by stress in children was reviewed and analyzed. To search for literary sources, the Scopus, PubMed, ResearchGate, Wiley Online Library, and Google Scholar databases were studied for 2016–2024, a total of 98 sources. Results. Modern etiopathogenetic factors for the occurrence of FGIR in children are described, with the key components of their biopsychosocial model highligh­ted. The influence of stressors on the development of mental disorders in children with FGIR, in particular emotional and volitional changes, is considered. We have demonstrated the role of serotonin and melatonin in the regulation of mood, emotions, sleep, beha­vior, anxiety, depression, etc. The importance of these neurotransmitters in the occurrence of gastrointestinal symptoms in FGIR is highlighted with modern approaches to the management of children with FGIR associated with emotional volitional disturbances caused by stress being considered. A promising therapeutic direction is identified — the use of supplements of certain neurotransmitters (in particular, serotonin and melatonin) in children with this pathology. Conclusions. The analyzed literature data demonstrate the heterogeneity of FGIR in children and the importance of stressors in their development. Neurotransmitters play a significant role in the formation of the response to stress and the course of FGIR associated with emotional volitional disturbances caused by stress in children. Data on the effectiveness of serotonin and melatonin supplementation in children with FGIR are few, so there is a need for further research on this issue in order to improve the effectiveness of treatment and the quality of life of these patients.
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Background: Epidemiological studies show that outdoor artificial light at night (ALAN) is linked to metabolic hazards, but its association with metabolic syndrome (MetS) remains unclear. We aimed to investigate the association of outdoor ALAN with MetS in middle-aged and elderly Chinese. Methods: From 2017-2020, we conducted a cross-sectional study in a total of 109,452 participants living in ten cities of eastern China. MetS was defined by fasting blood glucose (FG), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), blood pressure (BP), and waist circumference (WC). In 2021, we followed up 4395 participants without MetS at the baseline. Each participant's five-year average exposure to outdoor ALAN, as well as their exposure to green space type, were measured through matching to their address. Generalized linear models were used to assess the associations of outdoor ALAN with MetS. Stratified analyses were performed by sex, age, region, physical activity, and exposure to green space. Results: In the cross-sectional study, compared to the first quantile (Q1) of outdoor ALAN exposure, the odds ratios (ORs) of MetS were 1.156 [95 % confidence interval (CI): 1.111-1.203] and 1.073 (95 %CI: 1.021-1.128) respectively in the third and fourth quantiles (Q3, Q4) of outdoor ALAN exposure. The follow-up study found that, compared to the first quantile (Q1) of outdoor ALAN exposure, the OR of MetS in Q4 of ALAN exposure was 1.204 (95 %CI: 1.019-1.422). Adverse associations of ALAN with MetS components, including high FG, high TG, and obesity, were also found. Greater associations of ALAN with MetS were found in males, the elderly, urban residents, those with low frequency of physical activity, and those living in areas with low levels of grass cover and tree cover. Conclusions: Outdoor ALAN exposure is associated with an increased MetS risk, especially in males, the elderly, urban residents, those lacking physical activity, and those living in lower levels of grass cover and tree cover.
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The circadian rhythms evolved to anticipate and cope with cyclic changes in environmental conditions. This adaptive function is currently compromised by increasing levels of artificial light at night (ALAN), which can represent a risk for the development of diseases of civilisation. The causal links are not completely understood, and this featured review focuses on the chronodisruption of the neuroendocrine control of physiology and behaviour by dim ALAN. The published data indicate that low levels of ALAN (2–5 lux) can attenuate the molecular mechanisms generating circadian rhythms in the central oscillator, eliminate the rhythmic changes in dominant hormonal signals, such as melatonin, testosterone and vasopressin, and interfere with the circadian rhythm of the dominant glucocorticoid corticosterone in rodents. These changes are associated with a disturbed daily pattern of metabolic changes and behavioural rhythms in activity and food and water intake. The increasing levels of ALAN require the identification of the pathways mediating possible negative consequences on health to design effective mitigation strategies to eliminate or minimise the effects of light pollution.
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Artificial light is transforming the nighttime environment and quickly becoming one of the most pervasive pollutants on earth. Across taxa, light entrains endogenous circadian clocks that function to synchronize behavioral and physiological rhythms with natural photoperiod. Artificial light at night (ALAN) disrupts these photoperiodic cues and has consequences for humans and wildlife including sleep disruption, physiological stress and increased risk of cardiovascular disease. However, the mechanisms underlying organismal responses to dim ALAN, resembling light pollution, remain elusive. Light pollution exists in the environment at lower levels (<5 lux) than tested in many laboratory studies that link ALAN to circadian rhythm disruption. Few studies have linked dim ALAN to both the upstream regulators of circadian rhythms and downstream behavioral and physiological consequences. We exposed zebra finches (Taeniopygia gutatta) to dim ALAN (1.5 lux) and measured circadian expression of five pacemaker genes in central and peripheral tissues, plasma melatonin, locomotor activity, and biomarkers of cardiovascular health. ALAN caused an increase in nighttime activity and, for males, cardiac hypertrophy. Moreover, downstream effects were detectable after just short duration exposure (10 days) and at dim levels that mimic the intensity of environmental light pollution. However, ALAN did not affect circulating melatonin nor oscillations of circadian gene expression in the central clock (brain) or liver. These findings suggest that dim ALAN can alter behavior and physiology without strong shifts in the rhythmic expression of molecular circadian pacemakers. Approaches that focus on ecologically-relevant ALAN and link complex biological pathways are necessary to understand the mechanisms underlying vertebrate responses to light pollution.
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Most organisms use internal biological clocks to match behavioural and physiological processes to specific phases of the day–night cycle. Central to this is the synchronisation of internal processes across multiple organ systems. Environmental desynchrony (e.g. shift work) profoundly impacts human health, increasing cardiovascular disease and diabetes risk, yet the underlying mechanisms remain unclear. Here, we characterise the impact of desynchrony between the internal clock and the external light–dark (LD) cycle on mammalian physiology. We reveal that even under stable LD environments, phase misalignment has a profound effect, with decreased metabolic efficiency and disrupted cardiac function including prolonged QT interval duration. Importantly, physiological dysfunction is not driven by disrupted core clock function, nor by an internal desynchrony between organs, but rather the altered phase relationship between the internal clockwork and the external environment. We suggest phase misalignment as a major driver of pathologies associated with shift work, chronotype and social jetlag.
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Temporal organization of physiology is critical for human health. In the past, humans experienced predictable periods of daily light and dark driven by the solar day, which allowed for entrainment of intrinsic circadian rhythms to the environmental light–dark cycles. Since the adoption of electric light, however, pervasive exposure to nighttime lighting has blurred the boundaries of day and night, making it more difficult to synchronize biological processes. Many systems are under circadian control, including sleep–wake behavior, hormone secretion, cellular function and gene expression. Circadian disruption by nighttime light perturbs those processes and is associated with increasing incidence of certain cancers, metabolic dysfunction and mood disorders. This review focuses on the role of artificial light at night in mood regulation, including mechanisms through which aberrant light exposure affects the brain. Converging evidence suggests that circadian disruption alters the function of brain regions involved in emotion and mood regulation. This occurs through direct neural input from the clock or indirect effects, including altered neuroplasticity, neurotransmission and clock gene expression. Recently, the aberrant light exposure has been recognized for its health effects. This review summarizes the evidence linking aberrant light exposure to mood.
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Cardiovascular parameters, such as blood pressure and heart rate, exhibit both circadian and ultradian rhythms which are important for the adequate functioning of the system. For a better understanding of possible negative effects of chronodisruption on the cardiovascular system we studied circadian and ultradian rhythms of blood pressure and heart rate in rats exposed to repeated 8 h phase advance shifts of photoperiod. The experiment lasted 12 weeks, with three shifts per week. Spectral power as a function of frequency for both circadian and harmonic ultradian rhythms was expressed as the circadian-ultradian power ratio. The circadian rhythms of blood pressure, heart rate and locomotor activity were recorded during the control light:dark (LD) regimen with higher values during the D in comparison with the L. Phase advance shifts resulted in a diminished circadian-ultradian power ratio for blood pressure, heart rate and locomotor activity indicating suppressed circadian control of these traits greater in heart rate than blood pressure. In conclusion, rats kept under irregular LD conditions have suppressed circadian control of heart rate, blood pressure and locomotor activity and rely more on an acute response to the LD regime. Their ability to anticipate regular loads can be weakened and in this way chronodisruption can contribute to the pathogenesis of cardiovascular diseases.
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With the exception of high latitudes, life has evolved under bright days and dark nights. Most organisms have developed endogenously driven circadian rhythms that are synchronized to this daily light/dark cycle. In recent years, humans have shifted away from the naturally occurring solar light cycle in favor of artificial and sometimes irregular light schedules produced by electric lighting. Exposure to unnatural light cycles is increasingly associated with obesity and metabolic syndrome; however, the means by which environmental lighting alters metabolism are poorly understood. Thus, we exposed mice to dim light at night and investigated changes in the circadian system and metabolism. Here we report that exposure to ecologically relevant levels of dim (5 lux) light at night altered core circadian clock rhythms in the hypothalamus at both the gene and protein level. Circadian rhythms in clock expression persisted during light at night; however, the amplitude of Per1 and Per2 rhythms was attenuated in the hypothalamus. Circadian oscillations were also altered in peripheral tissues critical for metabolic regulation. Exposure to dimly illuminated, as compared to dark, nights decreased the rhythmic expression in all but one of the core circadian clock genes assessed in the liver. Additionally, mice exposed to dim light at night attenuated Rev-Erb expression in the liver and adipose tissue. Changes in the circadian clock were associated with temporal alterations in feeding behavior and increased weight gain. These results are significant because they provide evidence that mild changes in environmental lighting can alter circadian and metabolic function. Detailed analysis of temporal changes induced by nighttime light exposure may provide insight into the onset and progression of obesity and metabolic syndrome, as well as other disorders involving sleep and circadian rhythm disruption.
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According to Aschoff s rule the period of free‐running circadian rhythms of nocturnal animals lengthens with increasing constant ambient light intensity. The present study investigated Aschoff s rule in relation to the endogenous circadian temperature rhythm using a recently developed mathematical model. Rats were exposed to various ambient light conditions while their free‐running sleep‐wake and temperature rhythms were recorded continuously. The results show that both frequency and endogenous amplitude were suppressed by light, indicating that circadian rhythmicity may disappear as a result of a suppression of the endogenous rhythm at long circadian cycle lengths. Furthermore, different light conditions producing significantly different free‐running periods were accompanied by virtually identical activity levels. Therefore, it is concluded that the effect of light on the free‐running period is the result of a direct modulation of the circadian system, rather than of indirect action by altering levels of locomotor activity.
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Circadian disruption is a common by-product of modern life. Although jet lag and shift work are well-documented challenges to circadian organization, many more subtle environmental changes cause circadian disruption. For example, frequent fluctuations in the timing of the sleep/wake schedule, as well as exposure to nighttime lighting, likely affect the circadian system. Most studies of these effects have focused on nocturnal rodents, which are very different from diurnal species with respect to their patterns of light exposure and the effects that light can have on their activity. Thus, the authors investigated the effect of nighttime light on behavior and the brain of a diurnal rodent, the Nile grass rat. Following 3 weeks of exposure to standard light/dark (LD; 14:10 light [~150 lux] /dark [0 lux]) or dim light at night (dLAN; 14:10 light [~150 lux] /dim [5 lux]), rats underwent behavioral testing, and hippocampal neurons within CA1, CA3, and the dentate gyrus (DG) were examined. Three behavioral effects of dLAN were observed: (1) decreased preference for a sucrose solution, (2) increased latency to float in a forced swim test, and (3) impaired learning and memory in the Barnes maze. Light at night also reduced dendritic length in DG and basilar CA1 dendrites. Dendritic length in the DG positively correlated with sucrose consumption in the sucrose anhedonia task. Nighttime light exposure did not disrupt the pattern of circadian locomotor activity, and all grass rats maintained a diurnal activity pattern. Together, these data suggest that exposure to dLAN can alter affective responses and impair cognition in a diurnal animal.
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Exposure to Artificial Light At Night (ALAN) results in a disruption of the circadian system, which is deleterious to health. In industrialized countries, 75% of the total workforce is estimated to have been involved in shift work and night work. Epidemiologic studies, mainly of nurses, have revealed an association between sustained night work and a 50–100% higher incidence of breast cancer. The potential and multifactorial mechanisms of the effects include the suppression of melatonin secretion by ALAN, sleep deprivation, and circadian disruption.
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