Effects Of Constant Light Exposure Research Articles

Obesity alters circadian and behavioral responses to constant light in male mice

Exposure to artificial light during the night is known to promote disruption to the biological clock, which can lead to impaired mood and metabolism. Metabolic hormone secretion is modulated by the circadian pacemaker and recent research has shown that hormones such as insulin and leptin can also directly affect behavioral outcomes and the circadian clock. In turn, obesity itself is known to modulate the circadian rhythm and alter emotionality. This study investigated the behavioral and metabolic effects of constant light exposure in two models of obesity – a leptin null mutant (OB) and diet-induced obesity via high-fat diet. For both experiments, mice were placed into either a standard Light:Dark cycle (LD) or constant light (LL) and their circadian locomotor rhythms were continuously monitored. After 10 weeks of exposure to their respective lighting conditions, all mice were subjected to an open field assay to assess their explorative behaviors. Their metabolic hormone levels and inflammation levels were also measured. Behaviorally, exposure to constant light led to increased period lengthening and open field activity in the lean mice compared to both obesity models. Metabolically, LL led to increased cytokine levels and poorer metabolic outcomes in both lean and obese mice, sometimes exacerbating the metabolic issues in the obese mice, independent of weight gain. This study illustrates that LL can produce altered behavioral and physiological outcomes, even in lean mice. These results also indicate that obesity induced by different reasons can lead to shortened circadian rhythmicity and exploratory activity when exposed to chronic light.

The Effect of Light Interventions on Nap Quality and Subjective Alertness

The human eyes can perceive light even when napping during the day. In order to further investigate the effects of constant light exposure during napping on nap quality and subjective alertness, seven lighting conditions were designed in this paper, L0 (darkness), L1 (60 lx, 2800 k), L2 (300 lx, 2800 k), L3 (600 lx, 2800 k), L4 (60 lx, 5800 k), L5 (300 lx, 5800 k), L6 (600 lx, 5800 k). 12 participants were invited to perform a 30-minute light intervention nap experiment. Participants' Pittsburgh Sleep Quality Index (PSQI), Electroencephalographic (EEG), Karolinska Sleepiness Scale (KSS), skin temperature, and heart rate data were recorded. The results show that at L2 afternoon nap, θ band share is higher than other lighting conditions. At L6 afternoon nap, the δ band share was the lowest. High illuminance and low CCT significantly affected immediate subjective alertness during nap wakefulness, but reduced afternoon alertness was not related to light during nap. Although post-nap vigilance was lowest in L0 darkness, it rose rapidly to a maximum within 30 min of waking. From 0-25 min of napping, heart rate decreased significantly at L1 vs. L4, and skin temperature increased significantly at L2 vs. L5. None of the seven lighting conditions (L0-L6) inhibited participants' napping to a greater extent, and high illuminance and high colour temperature did not significantly increase the level of nap arousal (25-30 min).

Chronic constant light exposure aggravates high fat diet-induced renal injury in rats.

Obesity-related kidney disease is now recognized as a global health issue, with a substantial number of patients developing progressive renal failure and end-stage renal disease. Interestingly, recent studies indicate light pollution is a novel environmental risk factor for chronic kidney disease. However, the impact of light pollution on obesity-related kidney disease remains largely unknown, with its underlying mechanism insufficiently explained. Renal hypoxia induced factor 1α (HIF1α) is critical in the development of glomerulosclerosis and renal fibrosis. The present study explored effects of constant light exposure on high fat diet (HFD) -induced renal injury and its association with HIF1α signal pathway. Thirty-two male Sprague Dawley rats were divided into four groups according to diet (HFD or normal chow diet) and light cycles (light/dark or constant light). After 16 weeks treatment, rats were sacrificed and pathophysiological assessments were performed. In normal chow fed rats, constant light exposure led to glucose abnormalities and dyslipidemia. In HFD fed rats, constant light exposure exacerbated obesity, glucose abnormalities, insulin resistance, dyslipidemia, renal functional decline, proteinuria, glomerulomegaly, renal inflammation and fibrosis. And, constant light exposure caused an increase in HIF1α and a decrease in prolyl hydroxylase domain 1 (PHD1) and PHD2 expression in kidneys of HFD-fed rats. Then, we demonstrated that BMAL1 bound directly to the promoters of PHD1 in mouse podocyte clone 5 cell line (MPC5) by ChIP assays. In conclusion, chronic constant light exposure aggravates HFD-induced renal injuries in rats, and it is associated with activation of HIF1α signal pathway.

Constant light exposure in early life induces m6A-mediated inhibition of IGF gene family in the chicken.

Insulin-like growth factor (IGF) family plays important roles in regulating the development of various organ systems through stimulating cell proliferation and differentiation. Photoperiod is an important factor affecting growth and development in the chicken, yet the effect of constant light exposure in early life on IGF1 and IGF2 expression in the chicken remains unclear. In this study, one-day-old chickens were kept in either constant light (24L:0D, LL) or natural photoperiod (12L:12D, LD) for the first week of life and then maintained in constant light from 8 to 21 d of age. Constant light exposure in early life reduced mRNA expression of IGF gene family, including mRNA expression of IGF1, IGF2, and IGF2 binding proteins, in the hippocampus, hypothalamus, and liver of chickens at both 7 and 21 d of age. Moreover, constant light exposure increased mRNA expression of genes involved in RNA methylation N6-methyladenosine (m6A) in a tissue-specific manner. Interestingly, higher m6A on 3'UTR of IGF2 mRNA coincides with lower IGF2 mRNA, indicating a possible role of m6A in the post-transcriptional regulation of IGF2 expression in the hippocampus, hypothalamus, and liver of chickens. These findings suggest a m6A-mediated gene regulation of IGF gene family in different organs of chicken and expand our knowledge on mechanism of gene regulation in response to early life experience.

Constant light exposure alters gut microbiota and short-/medium-chain fatty acids and aggravates PCOS-like traits in HFD-fed rats.

This study investigated the effects of constant light exposure on polycystic ovary syndrome (PCOS)-like endocrine and metabolic changes in high-fat diet (HFD)-fed rats and to elucidate the related microbiotic mechanisms. A total of 32 female Sprague-Dawley rats were divided into four groups (n=8 each): rats on a normal chow diet with standard light-dark cycle, rats on a normal chow diet with constant light exposure, rats on an HFD with standard light-dark cycle, and rats on an HFD with constant light exposure. After 16 weeks of treatment, changes in anthropometric parameters, estrous cycle, hormone profiles, ovarian pathology, and gut microbiota and short-/medium-chain fatty acids in colon contents were assessed. Constant light exposure aggravated PCOS-like phenotypes in HFD-fed rats, such as hyperandrogenism, disrupted estrous cycle, and polycystic ovaries. Additionally, constant light exposure and an HFD synergized to decrease α-diversity of gut microbiota, create a reduced abundance of Ruminococcus genus, and create an increased abundance of Firmicutes and the Firmicutes/Bacteroidetes ratio. In HFD-fed rats, the group with constant light exposure had an increase in propionate acid and a decrease in total medium-chain fatty acids in colon contents compared with the standard light-dark cycle group. Constant light exposure causes gut dysbiosis, alters production of short- and medium-chain fatty acids, and aggravates PCOS-like traits in HFD-fed rats.

Effects of constant light exposure on allergic and irritant contact dermatitis in mice reared under constant light conditions.

Environmental light levels can affect physiological functions, such as general activity, body temperature and metabolism. Irregular lifestyles, such as those involving exposure to light during the night, can exacerbate the clinical symptoms of several inflammatory skin diseases. However, the effects of constant light exposure on immune responses are not fully understood. This study aimed to elucidate the effects of constant light exposure on two major types of skin reactions, allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD). BALB/c mice were kept under constant light conditions or a normal light and dark cycle, and their ACD and ICD responses were assessed after the topical application of 2,4,6-trinitro-1-chlorobenzene and croton oil, respectively, to the ear skin. Interestingly, in both ACD and ICD, the ear-swelling response and local leukocyte infiltration were aggravated by constant exposure to light, which has previously been shown to severely disturb the behavioural rhythms of mice. In ACD, these findings were accompanied by increases in the numbers of degranulated mast cells and eosinophils. These results suggest that constant light exposure intensifies allergic and non-allergic skin inflammation.

Constant Light Exposure Alters Gut Microbiota and Promotes the Progression of Steatohepatitis in High Fat Diet Rats

BackgroundNon-alcoholic fatty liver disease (NAFLD) poses a significant health concern worldwide. With the progression of urbanization, light pollution may be a previously unrecognized risk factor for NAFLD/NASH development. However, the role of light pollution on NAFLD is insufficiently understood, and the underlying mechanism remains unclear. Interestingly, recent studies indicate the gut microbiota affects NAFLD/NASH development. Therefore, the present study explored effects of constant light exposure on NAFLD and its related microbiotic mechanisms.Materials and MethodsTwenty-eight SD male rats were divided into four groups (n = 7 each): rats fed a normal chow diet, and exposed to standard light-dark cycle (ND-LD); rats fed a normal chow diet, and exposed to constant light (ND-LL); rats fed a high fat diet, and exposed to standard light-dark cycle (HFD-LD); and rats on a high fat diet, and exposed to constant light (HFD-LL). Body weight, hepatic pathophysiology, gut microbiota, and short/medium chain fatty acids in colon contents, serum lipopolysaccharide (LPS), and liver LPS-binding protein (LBP) mRNA expression were documented post intervention and compared among groups.ResultIn normal chow fed groups, rats exposed to constant light displayed glucose abnormalities and dyslipidemia. In HFD-fed rats, constant light exposure exacerbated glucose abnormalities, insulin resistance, inflammation, and liver steatohepatitis. Constant light exposure altered composition of gut microbiota in both normal chow and HFD fed rats. Compared with HFD-LD group, HFD-LL rats displayed less Butyricicoccus, Clostridium, and Turicibacter, butyrate levels in colon contents, decreased colon expression of occludin-1 and zonula occluden−1 (ZO-1), and increased serum LPS and liver LBP mRNA expression.ConclusionConstant light exposure impacts gut microbiota and its metabolic products, impairs gut barrier function and gut-liver axis, promotes NAFLD/NASH progression in HFD rats.

Changes in the Inner Retinal Cells after Intense and Constant Light Exposure in Sprague‐Dawley Rats

Light insult causes photoreceptor death. Few studies reported that continuous exposure to light affects horizontal, Müller and ganglion cells. We aimed to see the effect of constant light exposure on bipolar and amacrine cells. Adult Sprague-Dawley rats were exposed to 300 or 3000 lux for 7days in 12-h light: 12-h dark cycles (12L:12D). The latter group was then exposed to 24L:0D for 48h to induce significant damage. The same animals were reverted to 300lux and reared for 15days in 12L:12D cycles. They were sacrificed on different days to find the degree of retinal recovery, if any, from light injury. Besides photoreceptor death, continuous light for 48h resulted in downregulation of parvalbumin in amacrine cells and recoverin in cone bipolar cells (CBC). Rod bipolar cells (RBC) maintained an unaltered pattern of PKC-α expression. Upon reversal, there were increased expressions of parvalbumin in amacrine cells and recoverin in CBC, while RBC showed an increasing trend of PKC-α expression. The data show that damage in bipolar and amacrine cells after exposure to intense, continuous light can be ameliorated upon reversal to normal LD cycles to which the animals were initially acclimated to.

Effects of constant light exposure on sphingolipidomics and progression of NASH in high‐fat‐fed rats

Non-alcoholic fatty liver disease (NAFLD) is a growing public health concern worldwide. With the progression of urbanization, light pollution is becoming an inevitable risk factor for NAFLD. However, the role of light pollution on NAFLD is insufficiently understood, and the underlying mechanism remains unclear. The present study explored effects of constant light exposure on NAFLD and elucidated its related mechanisms. Thirty-two male Sprague Dawley rats were divided into four groups (n=8 each): (i) rats on a normal diet exposed to standard light-dark cycle (ND-LD); (ii) rats on a normal diet exposed to constant light (ND-LL); (iii) rats on a high-fat diet exposed to standard light-dark cycle (HFD-LD); and (iv) and rats on a high-fat diet exposed to constant light (HFD-LL). After 12weeks of treatment, rats were sacrificed and pathophysiological assessments were performed. Targeted lipidomics was used to measure sphingolipids, including ceramides, glucosylceramides, and lactosylceramides, sphingomyelins, and sphingosine-1-phosphates in plasma and liver tissues. In normal chow rats, constant light exposure led to glucose abnormalities and dyslipidemia. In high-fat-fed rats, constant light exposure exacerbated glucose abnormalities, dyslipidemia, insulin resistance, and inflammation and aggravated steatohepatitis. Compared with HFD-LD rats, HFD-LL had decreased plasma sphingosine-1-phosphate and elevated liver concentrations of total ceramide and specific ceramide species (ceramide d18:0/24:0, ceramide d18:1/22:0, ceramide d18:1/24:0, and ceramide d18:1/24:1), which were associated with increased hepatocyte apoptosis. Constant light exposure causes dysregulation of sphingolipids and promotes steatohepatitis in high-fat-fed rats.

Effects of constant light exposure on obesity in high fat diet rats

Objective To observe the effects of constant light exposure on the obesity in high fat diet rats. Methods Thirty-two male SD rats were randomly divided into four groups : rats on a normal chow exposed to standard light-dark cycle (group A), rats on a normal chow exposed to constant light (group B), rats on a high fat diet exposed to standard light-dark cycle (group C), and rats on a high fat diet exposed to constant light (group D). Body weights and food intakes were recorded weekly throughout the 12-week study. Body weight, fat mass, visceral adipose tissue weight, intraperitoneal glucose tolerance test (IPGTT) results, insulin resistance parameters, serum lipids and levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) were compared among groups. Epididymal adipose tissues mRNA expression of circadian clock genes, i. e. clock, bmal1, rorα, rev-erbα, cry1, per1, and per2 were analyzed by realtime PCR. Results From the 9th week, body weights of rats in group D were significantly higher than those in group C (all P<0.05). At the 12th week, area under curve of IPGTT (AUC-IPGTT) in groups B, C, and D were significantly higher than that in group A. AUC-IPGTT in group D was significantly higher than that in group C (all P<0.05). Compared with group C, a significant increase in fat mass, visceral adipose tissue weight, homeostasis model assessment for insulin resistance, serum cholesterol, TNF-α levels were observed in group D (all P<0.05). And a significant decrease in quantitative insulin sensitivity check index (QUICKI) and high density lipoprotein-cholesterol were observed in group D in comparison with group C (both P<0.05). Circadian clock genes (clock, rorα, rev-erbα, cry1, per1) mRNA expressions in group B and D were significantly different from those in group A (all P<0.05) . Expression of cry1 in group D was significantly higher than that in group C. In group C, rev-erbα mRNA expression was significantly down-regulated in comparison with group A (P<0.05). Conclusion Constant light exposure exaggerates obesity, glycolipid metabolism abnormality, inflammation, and insulin resistance in high fat diet rats. (Chin J Endocrinol Metab, 2017, 33: 1057-1062) Key words: Constant light exposure; High fat diet; Obesity; Insulin resistance; Circadian clock disruption

015 Effects of constant light exposure on contact hypersensitivity in mice

015 Effects of constant light exposure on contact hypersensitivity in mice

025 Effects of constant light exposure on the immune tolerance development in mice

025 Effects of constant light exposure on the immune tolerance development in mice

Histological and Immunohistochemical Study on the Effect of Constant Light Exposure on T Lymphocyte Subsets in the Thymus and Lymph Node of Male Albino Rats

Background: Today there is a widespread exposure to high levels of light at night. . This causes divergence from the natural environment and leads to significant implications on the circadian rhythm. Constant light exposure inhibits melatonin secretion and increases serum concentration of corticosterone. The immune system is very sensitive to stress.Aim of the Work: to study the effect of chronic exposure to constant light (as a model of stress) on the T lymphocytes populations and distribution in the thymus and lymph node.Material and Methods: animals were divided into two groups (10 rats each). The 1st group considered as control group, was kept on a day light-darkness for 12-12 h. The 2nd group was kept under complete artificial light for a period of 4 weeks. Thymus glands and the cervical lymph nodes of rats were removed and processed for haematoxylin and eosin, and immunohistochemical staining for CD3, CD4 and CD8.Results: lymphocytic depletion was noticed in the thymus and lymph nodes of the constant light exposed group. Also the distribution of CD3 and CD4 positive cells were altered in the lymph node of the same group.Conclusion: Constant light stress causes lymphocytic depletion and alters lymphoid cell subsets distribution both in the thymus and lymph nodes.

Environmental Circadian Disruption Worsens Neurologic Impairment and Inhibits Hippocampal Neurogenesis in Adult Rats After Traumatic Brain Injury

Circadian rhythms modulate many physiologic processes and behaviors. Therefore, their disruption causes a variety of potential adverse effects in humans and animals. Circadian disruption induced by constant light exposure has been discovered to produce pathophysiologic consequences after brain injury. However, the underlying mechanisms that lead to more severe impairment and disruption of neurophysiologic processes are not well understood. Here, we evaluated the effect of constant light exposure on the neurobehavioral impairment and survival of neurons in rats after traumatic brain injury (TBI). Sixty adult male Sprague-Dawley rats were subjected to a weight-drop model of TBI and then exposed to either a standard 12-/12-h light/dark cycle or a constant 24-h light/light cycle for 14days. Our results showed that 14days of constant light exposure after TBI significantly worsened the sensorimotor and cognitive deficits, which were associated with decreased body weight, impaired water and food intake, increased cortical lesion volume, and decreased neuronal survival. Furthermore, environmental circadian disruption inhibited cell proliferation and newborn cell survival and decreased immature cell production in rats subjected to the TBI model. We conclude that circadian disruption induced by constant light exposure worsens histologic and neurobehavioral impairment and inhibits neurogenesis in adult TBI rats. Our novel findings suggest that light exposure should be decreased and circadian rhythm reestablished in hospitalized TBI patients and that drugs and strategies that maintain circadian rhythm would offer a novel therapeutic option.

Keeping a ‘watch-full’ eye on metabolic disease

Evaluation of: Coomans CP, van den Berg SA, Houben T et al. Detrimental effects of constant light exposure and high-fat diet on circadian energy metabolism and insulin sensitivity. FASEB J. 27(4), 1721–1732 (2013).The synergy of metabolic homeostasis and biological clock function is at the forefront of chronobiology research. We now have a broad appreciation of the role that the molecular clock plays in glucose homeostasis, fat metabolism, oxidative stress and metabolic sensing. Furthermore, it is clear that environmental circadian disruption, as occurs during shiftwork, can have significant negative impacts on metabolism. The implication is that misalignment among central and peripheral oscillators facilitates the appearance of metabolic disease. Coomans and colleagues provide additional insight into the link between circadian disruption and metabolic disease. They have determined that brief exposure to constant light, a paradigm known to alter central clock function, disrupts circadian rhythms of insulin sensitivity and energy metabolism and increases bodyweight. Besides the basic implications for central clock control of glucose homeostasis, their data reveal that reduced output of the pacemaker may have implications for metabolic health in the aged.

Detrimental effects of constant light exposure and high‐fat diet on circadian energy metabolism and insulin sensitivity

Circadian rhythm disturbances are observed in, e.g., aging and neurodegenerative diseases and are associated with an increased incidence of obesity and diabetes. We subjected male C57Bl/6J mice to constant light [12-h light-light (LL) cycle] to examine the effects of a disturbed circadian rhythm on energy metabolism and insulin sensitivity. In vivo electrophysiological recordings in the central pacemaker of the suprachiasmatic nuclei (SCN) revealed an immediate reduction in rhythm amplitude, stabilizing at 44% of normal amplitude values after 4 d LL. Food intake was increased (+26%) and energy expenditure decreased (-13%), and we observed immediate body weight gain (d 4: +2.4%, d 14: +5.0%). Mixed model analysis revealed that weight gain developed more rapidly in response to LL as compared to high fat. After 4 wk in LL, the circadian pattern in feeding and energy expenditure was completely lost, despite continuing low-amplitude rhythms in the SCN and in behavior, whereas weight gain had stabilized. Hyperinsulinemic-euglycemic clamp analysis revealed complete abolishment of normal circadian variation in insulin sensitivity in LL. In conclusion, a reduction in amplitude of the SCN, to values previously observed in aged mice, is sufficient to induce a complete loss of circadian rhythms in energy metabolism and insulin sensitivity.

Expression of brain-derived neurotrophic factor in cholinergic and dopaminergic amacrine cells in the rat retina and the effects of constant light rearing

Brain-derived neurotrophic factor (BDNF) regulates many aspects of neuronal development, including survival, axonal and dendritic growth and synapse formation. Despite recent advances in our understanding of the functional significance of BDNF in retinal development, the retinal cell types expressing BDNF remains poorly defined. The goal of the present study was to determine the localization of BDNF in the mammalian retina, with special focus on the subtypes of amacrine cells, and to characterize, at the cellular level, the effects of constant light exposure during early postnatal period on retinal expression of BDNF. Retinas from 3-week-old rats reared in a normal light cycle or constant light were subjected to double immunofluorescence staining using antibodies to BDNF and retinal cell markers. BDNF immunoreactivity was localized to ganglion cells, cholinergic amacrine cells and dopaminergic amacrine cells, but not to AII amacrine cells regardless of rearing conditions. Approximately 75% of BDNF-positive cells in the inner nuclear layer were cholinergic amacrine cells in animals reared in a normal lighting condition. While BDNF immunoreactivity in ganglion cells and cholinergic amacrine cells was significantly increased by constant light rearing, which in dopaminergic amacrine cells was apparently unaltered. The overall structure of the retina and the density of ganglion cells, cholinergic amacrine cells and AII amacrine cells were unaffected by rearing conditions, whereas the density of dopaminergic amacrine cells was significantly increased by constant light rearing. The present results indicate that cholinergic amacrine cells are the primary source of BDNF in the inner nuclear layer of the rat retina and provide the first evidence that cholinergic amacrine cells may be involved in the visual activity-dependent regulation of retinal development through the production of BDNF. The present data also suggest that the production or survival of dopaminergic amacrine cells is regulated by early visual experience.

Protection of Photoreceptor Cells in Adult Rats from Light-induced Degeneration by Adaptation to Bright Cyclic Light

Light history has been shown to affect the susceptibility of the albino rat retina to the damaging effects of constant light exposure. Retinas of animals raised in relatively bright cyclic light are protected against light-induced degeneration compared with dim-reared animals. These effects were observed in animals raised from birth in bright cyclic light and are part of an adaptive response that protects photoreceptors from stress-induced degeneration. To determine if retinas of adult animals are capable of such adaptive changes or flexibility by switching between different light environments which do not pathologically damage photoreceptor cells, albino rats were maintained in less than 250lux cyclic light for more than 3 weeks. At 12–13 weeks of age, they were placed into 800lux cyclic light for 1 week, after which they were exposed to constant illumination of 1500lux for 1, 3 or 7 days. Retinal function was evaluated by electroretinography and photoreceptor cell death was quantified by measuring outer nuclear layer thickness. After 1 week in bright cyclic light, the retinas were completely protected against 1 day constant light exposure that significantly damaged retinas of animals without 800lux cyclic light adaptation. Significant protection was also observed in 3 day constant light exposed animals; limited protection occurred after 7 days exposure. These results indicate that the retinas of adult rats adapted to bright cyclic light within certain ranges that did not significantly damage photoreceptor cells are protected from constant light challenge. This phenomenon is a post-developmental response that demonstrates a remarkable plasticity of the retina. The mechanism(s) underlying the ability of this adaptation/flexibility in protecting photoreceptors could involve endogenous molecules that encompass many aspects of retinal cell and molecular biology and physiology. Identification of these molecules may provide insight into the development of therapeutic approaches to treat retinal degeneration.

The tumor promoting effect of constant light exposure on diethylnitrosamine-induced hepatocarcinogenesis in rats

The hypothesis that light-induced circadian clock suppression exerts a promoting effect on liver carcinogenesis was investigated in rats. Sixty-five male Wistar rats were given diethylnitrosamine (DEN, 10 mg/kg/day p.o.) for 6 weeks and were randomized into 3 groups. Rats from group 1 (N = 20) received DEN only. Rats from group 2 (N = 22) also received phenobarbital (pheno, 30 mg/rat/day p.o.) for 4 weeks as a promoting agent and rats from group 3 (N = 23) were exposed to continuous light. Three months after starting DEN treatment, urinary 6-sulfatoxymelatonin (αMT6s) excretion, a marker of circadian clock function, had lost its circadian rhythmicity in the LL group, with a 4-fold lower 24h mean than that found in the LDpheno and LD groups (8.0 ± 3.2 ng ml , 33.6 ± 3.1 ng ml and 34.3 ± 2.4 ng ml respectively; p from ANOVA < 0.001). Laparotomy was then performed. The proportion of rats with macroscopic nodules on liver surface was 72% (LD group), 89% (LDpheno group) and 95% (LL group) (p from χ 2 = 0.1). Nodules were more numerous and larger both in the LL group and in the LDpheno one as compared to the LD group (p from χ 2 < 0.05). All the rats died with hepatocellular carcinomas, with a median survival of 5 months, similar in all 3 groups. Light-induced circadian clock suppression exerted a promoting effect similar to that caused by phenobarbital in this model, yet through different effects on circadian system function.

The intergeniculate leaflet does not mediate the disruptive effects of constant light on circadian rhythms in the rat

Prolonged constant light exposure causes disruptions in circadian rhythms, resulting in splitting of circadian activity rhythms in hamsters and arrhythmicity in rats. Hamsters with lesions of the thalamic intergeniculate leaflet do not exhibit constant light-induced disruptions in rhythmicity. We have shown that circadian rhythms of rats with monosodium glutamate-induced neurotoxic damage to visual pathways persist under constant light, and hypothesized that monosodium glutamate damaged the retinogeniculate pathway, thus preventing constant light-induced arrhythmicity. The present study demonstrates, however, that the intergeniculate leaflet does not mediate these effects in rats. Rats with bilateral electrolytic intergeniculate leaflet lesions showed the same rate of disruption of circadian temperature rhythms as did sham-operated animals, housed under constant light. We also show that, unlike intergeniculate leaflet-lesioned rats, rats treated neonatally with monosodium glutamate exhibit neuropeptide Y fiber staining in the suprachiasmatic nucleus, indicating that the geniculohypothalamic tract is functionally intact following monosodium glutamate treatment. Taken together, these data demonstrate that the disruption of circadian rhythms during constant light exposure is not mediated directly via the geniculohypothalamic tract in rats. Whether this disruption in rhythmicity results from effects of constant light exposure on the circadian pacemaker, or is a direct effect of light on body temperature, is unknown. Retinal or collicular damage in monosodium glutamate-treated rats may render these animals insensitive to the disruptive effects of constant light.