scholarly journals Vision Dysfunction in Circadian Clock Gene Bmal Mice

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Humza Khan ◽  
Deepa Mathew ◽  
Qianyi Luo ◽  
Ashay Bhatwadekar

Background and Hypothesis: The circadian rhythm disruption due to shift work results in a range of disorders such as metabolic disturbances, obesity, cardiovascular diseases, and insulin resistance. Interestingly, the core clock gene Brain and Muscle ARNT-Like 1 (Bmal1), is dysfunctional in shift workers. We reasoned dysfunctional Bmal will affect normal vision function. To do so, a genetically modified mouse with disrupted Bmal was assessed for visual function. We hypothesized that Bmal knockout mice will exhibit reduced retinal functions such as impaired acuity, accommodation, and tracking. Experimental Design or Project Methods: The Bmal+/- mice were inbred and genotyped to obtain wild-types (WT), Bmal+/-, and Bmal-/-. To assess the retinal function, we performed electroretinogram (ERG) recordings at the zeitgeber times (ZT) of 0, 6, 12, and 18 which correspond to 7 AM, 1 PM, 7 PM, and 1 AM, respectively, under both scotopic and photopic conditions. The optokinetic response (OKR) assessments were measured in between ZT-3-ZT7. Results: Consistent with previous studies, the ‘a’ wave and ‘b’ wave amplitudes of WT mice demonstrated a circadian rhythm under scotopic condition. There was a decrease in ERG amplitude of Bmal+/-, and Bmal-/- when compared to the WT group. Under photopic conditions, the circadian peak of ERG amplitude was reversed for Bmal-/- when compared to both WT and Bmal+/- mice. The OKR assessment was decreased substantially for Bmal+/- (0.3748c/d), and Bmal-/- (0.3130c/d) as compared to the WT mice (0.4827c/d).  Conclusion and Potential Impact: Our studies demonstrate that the loss of Bmal leads to vision dysfunction possibly due to impaired rod and cone function. Furthermore, by using a mouse model of circadian rhythm dysfunction, we identified that individuals working on irregular shifts might be vulnerable to vision dysfunction, and our studies warrant timely testing of visual function and strategies for prevention of vision problems in shift workers.

Cephalalgia ◽  
2017 ◽  
Vol 38 (3) ◽  
pp. 496-502 ◽  
Author(s):  
Carmen Fourier ◽  
Caroline Ran ◽  
Margret Zinnegger ◽  
Anne-Sofie Johansson ◽  
Christina Sjöstrand ◽  
...  

Background Cluster headache is characterized by recurrent unilateral headache attacks of severe intensity. One of the main features in a majority of patients is a striking rhythmicity of attacks. The CLOCK ( Circadian Locomotor Output Cycles Kaput) gene encodes a transcription factor that serves as a basic driving force for circadian rhythm in humans and is therefore particularly interesting as a candidate gene for cluster headache. Methods We performed an association study on a large Swedish cluster headache case-control sample (449 patients and 677 controls) screening for three single nucleotide polymorphisms (SNPs) in the CLOCK gene implicated in diurnal preference (rs1801260) or sleep duration (rs11932595 and rs12649507), respectively. We further wanted to investigate the effect of identified associated SNPs on CLOCK gene expression. Results We found a significant association with rs12649507 and cluster headache ( p = 0.0069) and this data was strengthened when stratifying for reported diurnal rhythmicity of attacks ( p = 0.0009). We investigated the effect of rs12649507 on CLOCK gene expression in human primary fibroblast cultures and identified a significant increase in CLOCK mRNA expression ( p = 0.0232). Conclusions Our results strengthen the hypothesis of the involvement of circadian rhythm in cluster headache.


2010 ◽  
Vol 54 (7) ◽  
pp. 652-656 ◽  
Author(s):  
Luciana da Conceição Antunes ◽  
Manoela Neves da Jornada ◽  
Letícia Ramalho ◽  
Maria Paz Loayza Hidalgo

OBJECTIVE: Correlate shift work with body mass index (BMI), waist circumference, chronotype and depressive symptoms. SUBJECTS AND METHODS: This study comprising 14 shift workers and 13 day workers. Subjects were workers from the health area aged 25 to 60 years. Minor psychiatric disorders were accessed by Self Report Questionnaire (SRQ-20) and depressive symptoms by Beck Depression Inventory (BDI). Chronotype was accessed using Morningness-Eveningness Questionnaire (MEQ). Anthropometric measures were taken. RESULTS: Shift workers presented higher BMI (P = 0.03) and waist circumference (P = 0.004) than day workers. Years on shift work were significantly correlated to waist circumference (r = 0.43; P = 0.03) and age (r = 0.47; P = 0.02). Shift work was not correlated with depressive symptoms and chronotype. CONCLUSION: These results may suggest a role played by shift work on the development and/or the early clinic manifestations of metabolic disturbances, becoming a risk factor to metabolic syndrome.


Author(s):  
Sheng-Long Ding ◽  
Tai-Wei Zhang ◽  
Qi-Chen Zhang ◽  
Wang Ding ◽  
Ze-Fang Li ◽  
...  

AbstractNight shift workers with disordered rhythmic mechanical loading are more prone to intervertebral disc degeneration (IDD). Our results showed that circadian rhythm (CR) was dampened in degenerated and aged NP cells. Long-term environmental CR disruption promoted IDD in rats. Excessive mechanical strain disrupted the CR and inhibited the expression of core clock proteins. The inhibitory effect of mechanical loading on the expression of extracellular matrix genes could be reversed by BMAL1 overexpression in NP cells. The Rho/ROCK pathway was demonstrated to mediate the effect of mechanical stimulation on CR. Prolonged mechanical loading for 12 months affected intrinsic CR genes and induced IDD in a model of upright posture in a normal environment. Unexpectedly, mechanical loading further accelerated the IDD in an Light-Dark (LD) cycle-disrupted environment. These results indicated that intrinsic CR disruption might be a mechanism involved in overloading-induced IDD and a potential drug target for night shift workers.


2018 ◽  
Vol 165 (3) ◽  
pp. 331-333 ◽  
Author(s):  
N. V. Semenova ◽  
I. M. Madaeva ◽  
T. A. Bairova ◽  
R. M. Zhambalova ◽  
O. V. Kalyuzhnaya ◽  
...  

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
N I Bektas ◽  
G Akcay ◽  
N Derin ◽  
D Adiguzel ◽  
C Celik-Ozenci

Abstract Study question Are molecular clock genes (MCGs) expressed rhythmically in mouse placenta, and whether maternal circadian rhythm disruption (MCRD) is associated with intrauterine growth retardation (IUGR) through disturbing rhythmic expression of MCGs? Summary answer Maternal circadian disruption causes impaired rhythmic expression of MCGs (Bmal1, Clock, Npas2, Per1, Per2, Per3, Cry1, and Cry2) and IUGR during placenta development in mice. What is known already The world economy is based on a 24/7 society and shift work or jet travel across time zones disrupts circadian rhythm in pregnant women. Evidence indicates that gestational chrono-disruption results in IUGR. Mature mouse and human placenta express MCGs. There is no information in the literature on whether the MCG expression in the placenta is rhythmic or not and whether the rhythmic expression of MCGs is impaired due to MCRD during pregnancy. Also, it is not known whether the association with MCRD and IUGR is related to MCGs. Study design, size, duration Young adult female BALB/c mice were paired with males until vaginal plug formation was verified. Females were randomly assigned to two groups: control and phase-advance. Controls remained on a constant 12-hr light:12-hr dark cycle, whereas phase-advanced mice were subjected to 6-hr advances in the LD cycle every 5 days. Placentae (n = 1329) and fetuses were obtained from 144 mice at Zeitgeber time (ZT)0, ZT6, ZT12, and ZT18 days 12, 14, and 16 of pregnancy. Participants/materials, setting, methods The following analysis was performed: (i) open field test was used for locomotor activity evaluations to confirm MCRD, (ii) placenta/fetus weight ratio for evaluation of IUGR development, (iii) morphometric evaluation of placental compartments utilizing H&E staining (iv) gene expression analysis of MCGs utilizing qRT-PCR. One-way and Two-way ANOVA test followed by Holm-Sidak posthoc test was used for multiple comparisons. Values are expressed as mean ± standard error, and values below p < 0.05 were considered statistically significant. Main results and the role of chance Expression of MCGs (Bmal1, Clock, Npas2, Per1, Per2, Per3, Cry1, and Cry2) was rhythmic in the early and mature placenta development stages (days 12, 14, 16). Locomotor activity tests reveal that the total distance covered on the 16th day of pregnancy significantly decreased compared to the control group (p = 0.000158). The ratio of the time spent in the outer/inner quadrant, an anxiety indicator, significantly increased in the MCRD group on the 14th (p = 0.0351) and 16th days of pregnancy (p = 0.000329). While the number of fetuses was similar in both groups for all gestational days (p = 0.896), in the MCRD group, the fetus/placenta weight ratio decreased significantly on the 12th and 16th days of pregnancy (p < 0.001). Thus, IUGR developed due to MCRD. Histomorphometry analysis of the placental compartments revealed a significant reduction in the spongiotrophoblast layer’s size on all days of pregnancy and the labyrinth layer on day 16 (p < 0.05). Finally, the rhythmic expression MCGs were impaired in placentas obtained from MCRD groups on days 12th, 14th, 6th of pregnancy (p < 0.001). In conclusion, we found a robust relationship with the disturbed MCGs expression and occurrence of IUGR during a chrono-disrupted gestation. Limitations, reasons for caution Since this study was conducted in mice, care should be taken when translating the results to humans. Wider implications of the findings: Our results in mice are important for initiating basic science knowledge regarding the outcomes of maternal chrono-disruption. Moreover, research in the placenta of gestational chrono-disrupted mothers, such as shift-workers, are urgently needed to translate our findings into the clinic. Trial registration number TUBITAK–119S121 and Akdeniz University Research Projects Unit TYL–2018–3960


2019 ◽  
Vol 36 (6) ◽  
pp. 751-757 ◽  
Author(s):  
Aki Tomizawa ◽  
Kazuhiro Nogawa ◽  
Yuuka Watanabe ◽  
Mitsuhiro Oishi ◽  
Kumihiko Tanaka ◽  
...  

2019 ◽  
Vol 1 (2) ◽  
pp. 273-279 ◽  
Author(s):  
Francine Lu ◽  
Amanda Suggs ◽  
Harib Ezaldein ◽  
Jason Ya ◽  
Pingfu Fu ◽  
...  

Night shift workers may have a disrupted circadian rhythm, which may contribute to the development of skin disease. The purpose of this study was to determine whether there is a significant difference in the prevalence and severity of self-reported skin disease between “regular” day shift workers compared to “graveyard” night shift workers. We conducted surveys from 630 call center agents in Manila, the Philippines, and they were analyzed regarding demographics, medical history, dermatologic history, lifestyle, and sleep. No difference was found in the prevalence of skin disease between shifts. However, night shift workers were worse sleepers. When compared to good sleepers, poor sleepers had a higher prevalence of skin disease with worse severity. Graveyard shift workers with poor sleep may have increased skin disease severity.


1996 ◽  
Vol 6 (1) ◽  
pp. 81-86 ◽  
Author(s):  
H. Tabandeh ◽  
L. Ranganath ◽  
V. Marks

Hypoglycaemia symptoms are of particular interest in view of the importance of hypoglycaemia unawareness. Visual symptoms arising during acute hypoglycaemia may be the result of metabolic disturbances in the visual pathways within the central nervous system or impairment of the refractive apparatus of the eye and binocular function. This study investigated the effect of hypoglycaemia upon visual acuity, binocular interaction and contrast sensitivity. Various aspects of visual function were examined in ten normal subjects before, during and after acute insulin-induced hypoglycaemia. A simultaneous study of hypoglycaemic symptoms enabled us to relate the objective findings to the symptoms as reported by the subjects. Snellen visual acuity, fusion and stereopsis were not affected by hypoglycaemia. Five subjects noted visual disturbance. Eight developed significant impairment of contrast sensitivity, which closely matched the lowered blood glucose concentration. These observations suggest that hypoglycaemic visual symptoms are due to neuroglycopenia of central visual pathways rather than changes within the refractive apparatus or abnormality of binocular function. Although these symptoms are not a constant feature of the hypoglycaemic state, subtle impairment of visual function occurs in most cases. Contrast sensitivity testing can be useful for assessment of fine changes in visual function.


1970 ◽  
Vol 2 ◽  
pp. 34-37
Author(s):  
Md Abedur Rahman ◽  
Md Ruhul Amin ◽  
Momotaj Begum ◽  
Firoza Khatun ◽  
Montasir Islam ◽  
...  

Background: The present study was undertaken to evaluate the changes of serum lipid profile in apparently healthy shift workers and non shift workers to identify the possible high risk factors for developing atherosclerotic changes. Methods: Serum Total Cholesterol, Triglyceride, HDL-Cholesterol and LDL-Cholesterol levels were estimated and blood pressure was measured in apparently healthy adult shift worker and non shift worker participants. Total 60 subjects age ranged from 20-50 years were selected, of whom 30 were shift workers (Study) for at least one year and 30 were non shift workers (control). Height, weight and resting blood pressure of all the subjects were recorded before collection of blood. Blood samples were collected after over night fasting for estimation of serum lipid and lipoprotein levels and were measured by standard laboratory technique. Data were analyzed by unpaired ‘t' test. Results: The mean serum Total Cholesterol and LDL-Cholesterol levels were significantly higher in shift workers compared to those of non shift workers. Again mean serum Triglyceride and HDL-Cholesterol levels in the shift workers did not differ significantly from that of non shift workers. These changes may be related to internal desynchronization due to disruption of circadian rhythm. Conclusion: The changes in serum lipid and lipoprotein levels with the exception of HDL-Cholesterol and Triglyceride in the subjects engaged in shift work may put them at increased risk for coronary artery disease. Keywords: Circadian Rhythm; Lipid Profile; Shift-work   DOI:10.3329/jbsp.v2i0.982 J Bangladesh Soc Physiol. 2007 Dec;(2): 34-37.


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