Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice.
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ABSTRACT:
SUBMITTER: Lang V
PROVIDER: S-EPMC8598165 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Acute myocardial infarction and stroke occur more frequently in the morning, suggesting a role of the circadian clock in these main causes of death, secondary to atherosclerosis. OBJECTIVES:To investigate the expression of clock genes, apoptosis-related genes and atherosclerosis-related genes in the process of atherosclerosis. METHODS:Apolipoprotein E knockout (ApoE-/-) mice were used to establish animal models of early and advanced atherosclerosis. Real-time polymerase chain reaction, Western blotting and microarray assays were used to detect the expression of clock genes, apoptosis-related genes and atherosclerosis-related genes. RESULTS:Clock genes in ApoE-/- and C57BL/6J mouse hearts exhibited daily oscillations at the messenger RNA level. However, the expression level and rhythm between ApoE-/- and C57BL/6J mice were significantly different. Moreover, the changes became more significant as atherosclerosis developed. c-Myc and p53 genes exhibited circadian expression in C57BL/6J mice at messenger RNA and protein levels. However, the rhythm in ApoE-/- mice disappeared completely. Bcl-2 and Bax did not show daily rhythm in either strain of mouse. Aside from apoptosis-related genes, several atherosclerosis-related genes expressed time-dependent behaviour in C57BL/6J mice but not in ApoE-/- mice. CONCLUSIONS:Rhythm changes of clock genes, apoptosis-related genes and atherosclerosis-related genes may play important roles in atherosclerosis and its complications.
| S-EPMC2732375 | biostudies-literature
Project description:Several previous studies suggest that dysfunction of circadian rhythms may increase susceptibility to bipolar disorder (BP). We conducted an association study of five circadian genes (CRY2, PER1-3, and TIMELESS) in a family collection of 36 trios and 79 quads (Sample I), and 10 circadian genes (ARNTL, ARNTL2, BHLHB2, BHLHB3, CLOCK, CRY1, CSNK1D, CSNK1E, DBP, and NR1D1) in an extended family collection of 70 trios and 237 quads (Sample II), which includes the same 114 families but not necessarily the same individuals as Sample I. In Sample II, the Sibling-Transmission Disequilibrium Test (sib-tdt) analysis showed nominally significant association of BP with three SNPs within or near the CLOCK gene (rs534654, P = 0.0097; rs6850524, P = 0.012; rs4340844, P = 0.015). In addition, SNPs in the ARNTL2, CLOCK, DBP, and TIMELESS genes and haplotypes in the ARNTL, CLOCK, CSNK1E, and TIMELESS genes showed suggestive evidence of association with several circadian phenotypes identified in BP patients. However, none of these associations reached gene-wide or experiment-wide significance after correction for multiple-testing. A multi-locus interaction between rs6442925 in the 5' upstream of BHLHB2, rs1534891 in CSNK1E, and rs534654 near the 3' end of the CLOCK gene, however, is significantly associated with BP (P = 0.00000172). It remains significant after correcting for multiple testing using the False Discovery Rate method. Our results indicate an interaction between three circadian genes in susceptibility to bipolar disorder.
| S-EPMC2574897 | biostudies-literature
Project description:UNLABELLED:Transient hepatomegaly often accompanies acute bacterial infections. Reversible, dose-dependent hepatomegaly also occurs when animals are given intravenous infusions of bacterial lipopolysaccharide (LPS). We found that recovery from LPS-induced hepatomegaly requires a host enzyme, acyloxyacyl hydrolase (AOAH), that inactivates LPS. When we challenged Aoah(-/-) mice with low doses of LPS or gram-negative bacteria, their livers remained enlarged (as much as 80% above normal) many weeks longer than did the livers of Aoah(+/+) animals. When compared with livers from LPS-primed Aoah(+/+) mice, LPS-primed Aoah(-/-) livers had (1) more numerous and larger Kupffer cells, (2) intrasinusoidal leukocyte aggregates and activated sinusoidal endothelial cells, and (3) sustained production of interleukin (IL)-10 and messenger RNAs (mRNAs) for tumor necrosis factor (TNF), IL-10, and IRAK-M. Depleting Kupffer cells decreased the liver enlargement by ?40%, whereas depletion of neutrophils, dendritic cells, natural killer (NK) cells, NK-T cells, or B cells had no effect. Pretreatment with dexamethasone almost completely prevented prolonged hepatomegaly in Aoah(-/-) mice, whereas neutralizing TNF or interleukin-1? was only partially effective. In contrast, an antagonistic antibody to the IL-10 receptor increased LPS-induced hepatomegaly by as much as 50%. CONCLUSION:our findings suggest that persistently active LPS induces Kupffer cells to elaborate mediators that promote the accumulation of leukocytes within enlarged sinusoids. Large increases in IL-10 and several other modulatory molecules are unable to prevent prolonged hepatomegaly in mice that cannot inactivate LPS. The striking findings in this mouse model should encourage studies to find out how AOAH contributes to human liver physiology and disease.
| S-EPMC3188384 | biostudies-literature
Project description:One hundred ninety wildtype male C57BL/6J mice age 7-10 weeks were purchased from Jackson Laboratory and entrained to a 12:12 light:dark cycle for 2 weeks. Mice were placed in light-tight boxes on a 12:12 LD cycle for 4 weeks, then released into constant darkness. Starting 30 hours after entry into DD (CT18), tissues from 5 (skeletal muscle) or 10 (liver or SCN) wildtype mice were collected every 4 hours for 48 hours, for a total of 12 timepoints. At timepoints 34 through 58 hours in DD, tissues from age-matched male C57BL/6J Clock/Clock homozygous mutant mice that had been treated with the same light entrainment protocol as the wildtype were collected. Tissues were collected from 5 Clock/Clock mutants at each timepoint except for 34 and 46 hours after the onset of DD, when tissues from 10 Clock/Clock mice were collected and run as independent replicates. Mice were sacrificed by cervical dislocation, and the optic nerves were severed in complete darkness; brain dissection was performed using illumination from an infrared viewer (FJW Industries, Palatine, IL). SCNs were dissected out, pooled at a density of 5 per tube in 100 ul RNAlater (Ambion, Austin, TX), frozen on dry ice, and stored at â80 degrees C until use. Keywords: SuperSeries This reference Series links data in the following related Series: GSE3746 Circadian skeletal muscle_wt and Clock mutants GSE3748 Circadian liver_wt and Clock mutants
2010-06-12 | E-GEOD-3751 | biostudies-arrayexpress
Project description:Molecular analysis of circadian rhythm in mice. Liver tissue of wildtype, Clock mutant and Cry deficient C57BL/6 8- to 10-week-old male mice examined. Keywords = circadian rhythm Keywords: other
2003-11-08 | GSE454 | GEO
Project description:One hundred ninety wildtype male C57BL/6J mice age 7-10 weeks were purchased from Jackson Laboratory and entrained to a 12:12 light:dark cycle for 2 weeks. Mice were placed in light-tight boxes on a 12:12 LD cycle for 4 weeks, then released into constant darkness. Starting 30 hours after entry into DD (CT18), tissues from 5 (skeletal muscle) or 10 (liver or SCN) wildtype mice were collected every 4 hours for 48 hours, for a total of 12 timepoints. At timepoints 34 through 58 hours in DD, tissues from age-matched male C57BL/6J Clock/Clock homozygous mutant mice that had been treated with the same light entrainment protocol as the wildtype were collected. Tissues were collected from 5 Clock/Clock mutants at each timepoint except for 34 and 46 hours after the onset of DD, when tissues from 10 Clock/Clock mice were collected and run as independent replicates. Mice were sacrificed by cervical dislocation, and the optic nerves were severed in complete darkness; brain dissection was performed using illumination from an infrared viewer (FJW Industries, Palatine, IL). SCNs were dissected out, pooled at a density of 5 per tube in 100 ul RNAlater (Ambion, Austin, TX), frozen on dry ice, and stored at –80 degrees C until use. This SuperSeries is composed of the SubSeries listed below.
2007-02-07 | GSE3751 | GEO
Project description:Epilepsy is a neurological disorder characterized by unpredictable seizures, which are bursts of electrical activity that temporarily affect the brain. Cereblon (CRBN), a DCAFs (DDB1 and CUL4-associated factors), is a well-established protein associated with human mental retardation. Being a substrate receptor of the cullin-RING E3 ubiquitin ligase (CRL) 4 complex, CRBN mediates ubiquitination of several substrates and conducts multiple biological processes. In the central nervous system, the largeconductance Ca2+-activated K+ (BKCa) channel, which is the substrate of CRBN, is an important regulator of epilepsy. Despite the functional role and importance of CRBN in the brain, direct injection of pentylenetetrazole (PTZ) to induce seizures in CRBN knock-out mice has not been challenged. In this study, we investigated the effect of PTZ in CRBN knock-out mice. Here, we demonstrate that, compared with WT mice, CRBN knock-out mice do not show the intensification of seizures by PTZ induction. Moreover, electroencephalography recordings were also performed in the brains of both WT and CRBN knockout mice to identify the absence of significant differences in the pattern of seizure activities. Consistently, immunoblot analysis for validating the protein level of the CRL4 complex containing CRBN (CRL4Crbn) in the mouse brain was carried out. Taken together, we found that the deficiency of CRBN does not affect PTZ-induced seizure. [BMB Reports 2020; 53(9): 484-489].
| S-EPMC7526979 | biostudies-literature
Project description:The circadian clock comprises a set of genes involved in cell-autonomous transcriptional feedback loops that orchestrate the expression of a range of downstream genes, driving circadian patterns of behavior. Cognitive dysfunction, mood disorders, anxiety disorders, and substance abuse disorders have been associated with disruptions in circadian rhythm and circadian clock genes, but the causal relationship of these associations is still poorly understood. In the present study, we investigate the effect of genetic disruption of the circadian clock, through deletion of both paralogs of the core gene cryptochrome (Cry1 and Cry2). Mice lacking Cry1 and Cry2 (Cry1(-/-)Cry2(-/-) ) displayed attenuated dark phase and novelty-induced locomotor activity. Moreover, they showed impaired recognition memory but intact fear memory. Depression-related behaviors in the forced swim test or sucrose preference tests were unaffected but Cry1(-/-)Cry2(-/-) mice displayed increased anxiety in the open field and elevated plus maze tests. Finally, hyperlocomotion and striatal phosphorylation of extracellular signal-regulated kinase (ERK) induced by a single cocaine administration are strongly reduced in Cry1(-/-)Cry2(-/-) mice. Interestingly, only some behavioral measures were affected in mice lacking either Cry1 or Cry2. Notably, recognition memory was impaired in both Cry1(-/-)Cry2(+/+) and Cry1(+/+)Cry2(-/-) mice. Moreover, we further observed elevated anxiety in Cry1(-/-)Cry2(+/+) and Cry1(+/+)Cry2(-/-) mice. Our data indicate that beyond their role in the control of circadian rhythm, cryptochrome genes have a direct influence in cognitive function, anxiety-related behaviors and sensitivity to psychostimulant drugs.
| S-EPMC3807562 | biostudies-literature
Project description:To analyze in severely obese women the circadian expression of the clock genes hPer2, hBmal1, and hCry1 in explants from subcutaneous (SAT) and visceral (VAT) adipose tissue (AT), in order to elucidate whether this circadian clockwork can oscillate accurately and independently of the suprachiasmatic nucleus (SCN) and if glucocorticoid metabolism-related genes such as glucocorticoid receptor (hGr) and 11beta-hydroxysteroid dehydrogenase 1 (h11 beta Hsd1) and the transcription factor peroxisome proliferator activated receptor gamma (hPPAR gamma) are part of the clock controlled genes. AT biopsies were obtained from morbid obese patients (BMI > or =40 kg/m(2)) (n = 7). Anthropometric variables were measured and fasting plasma lipids and lipoprotein concentrations were analyzed. In order to carry out rhythmic expression analysis, AT explants were cultured during 24 h and gene expression was performed at the following times (T): 0, 6, 12, and 18 h, with quantitative real-time PCR. Clock genes oscillated accurately and independently of the SCN in AT explants. Their intrinsic oscillatory mechanism regulated the timing of other genes such as hPPAR gamma and glucocorticoid-related genes. Circadian patterns differed between VAT and SAT. Correlation analyses between the genetic circadian oscillation and components of the metabolic syndrome (MetS) revealed that subjects with a higher sagittal diameter showed an increased circadian variability in hPer2 expression (r = 0.91; P = 0.031) and hBmal1 (r = 0.90; P = 0.040). Data demonstrate the presence of peripheral circadian oscillators in human AT independently of the central circadian control mechanism. This knowledge paves the way for a better understanding of the circadian contribution to medical conditions such as obesity and MetS.
| S-EPMC4429875 | biostudies-literature
Project description:Circadian rhythm in clock mutants
| PRJNA93919 | ENA