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Objective:To explore the modulatory effects of GSK-3β/β-catenin signaling pathway on anxiety- and depression-like behavior of mice induced by chronic sleep deprivation (CSD).Methods:Forty-eight 10-week-old C57BL/6J male mice were selected and randomly divided into four groups(with 12 mice in each group): control group, inhibitor-only group (LiCl), chronic sleep deprivation group (CSD) and inhibitor with CSD group (LiCl+ CSD). Elevated plus maze (EPM) and forced swimming test (FST) were used to evaluate the behavior of mice, HE staining was used to observe the pathological morphological changes of hippocampal neurons, and Western blot was used to detect the protein expressions of β-catenin, GSK-3β and p-GSK-3β in hippocampal tissues. SPSS 22.0 software was used for independent sample t-test and one way ANOVA. Results:After modeling, the body weight of mice in the CSD group ((26.53±0.76)g) was significantly lower than that of the control group ((28.00±0.37)g) ( q=4.119, P=0.041), and the body weight in the LiCl+ CSD group ((28.04±0.86)g) was improved compared with CSD group ( q=4.240, P=0.036). In EPM, the ratio of the entering times and the proportion of the staying time in the open arm in the CSD group ((48.44±9.16)%) and ((16.47±10.42)%) were significantly lower than those in the control group ((68.92±11.71)% and (42.93±15.89)%) ( q=4.660, P=0.018, q=4.346, P=0.029), but the staying time in the open arm in the LiCl+ CSD group ((32.92±12.05)%) was significantly higher than that in the CSD group ( q=2.432, P=0.038). In FST, the percentage of floating immobility time of the mice in the CSD group ((55.00±5.36)%) was significantly longer than that of the control group ((39.95±2.87)%) ( P=0.023), which was decreased significantly in the LiCl+ CSD group ((42.00±7.92)%) than that in the CSD group ( P=0.040). Western blot results showed that, the expressions of p-GSK-3β and β-catenin in the hippocampus of CSD group were decreased significantly ( P=0.040, P=0.008), while the expression of GSK-3β was significantly increased than that of the control group ( P<0.001). Both p-GSK-3β and β-catenin were significantly reversed in CSD+ LiCl group than that in CSD ( P=0.034, P=0.038). Conclusion:The GSK-3β/β-catenin signaling pathway may be involved in the regulation of CSD-induced anxiety and depression-like behaviors in mice.
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@#Objective Investigated the influences of chronic sleep deprivation on the expression α7-nAChR and the activity of its downstream PI3K/AKT/GSK-3β pathway in neuroglia in mice.Methods Adult C57BL/6J mice aged 7-8 weeks were randomly divided into three groups，control（CC）group，chronic sleep deprivation（SD） group，chronic sleep deprivation + intraperitoneal injection α7-nAChR agonists PHA-543613（SD + PHA - 543613） group.The protein expression of α7 -nAChR,p-AKT,p-GSK-3β,Nrf-2,HO-1 in mice hippocampus were examined by Western Blot，the gene expression of α7 -nAChR and the gene expression of TNF-α,IL-1β,IFN-γ,MCP-1,Arg-1,CD206,TGF-β,YM-1 were examined by Rt-PCR；the expression of α7-nAChR on astrocytes and microglias in mice hippocampus were assesed by double-labeled immunofluorescence.Spatial learning and memory was assessed by morris water maze （MWM） test.Results After chronic sleep deprivation for 7 days，the expression of α7-nAChR protein，mRNA in SD group decreased significantly when compared with CC group（P=0.001,P=0.038）;the expression of protein p-AKT decreased in SD group compared with CC group（P=0.019）,while the expression of protein p-GSK-3β increased in SD group compared with CC group（P=0.011）.Afterα7-nAChR agonists PHA-543613 treatment,the expression of α-7 nAChR on astrocytes increased significantly when compared with SD group（P=0.027，the expression of p-AKT and p-GSK-3βincreased when compared with SD group（P=0.047,P=0.017.At the same time，the expression of Nrf-2，HO-1 and anti-inflammatory factors（CD206，TGF-β）increased significantly compared with SD group（P=0.020,P=0.016，P<0.01,P<0.01），while the expression of inflammatory factors（TNF-α，MCP-1） decreased compared with SD group（P<0.01）.After α7-nAChR agonists PHA-543613 treatment，the escape latency at the end of experiment was decreased，the frequency of crossing platforms and the time in the target quadrant was prolonged compared to the SD group（P=0.000,P=0.000,P=0.001）.Conclusion Stimulation of α7-nAChR reduces inflammation and oxidative stress via activation of PI3K/AKT /GSK-3β after chronic sleep deprivation.
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BACKGROUND: In modern societies, sleep deprivation is a serious health problem. This problem could be induced by a variety of reasons, including lifestyle habits or neurological disorders. Chronic sleep deprivation (CSD) could have complex biological consequences, such as changes in neural autonomic control, increased oxidative stress, and inflammatory responses. The superior cervical ganglion (SCG) is an important sympathetic component of the autonomic nervous system. CSD can lead to a wide range of neurological consequences in SCG, which mainly supply innervations to circadian system and other structures. As the active component of Curcuma longa, curcumin possesses many therapeutic properties; including neuroprotective. This study aimed to evaluate the effect of CSD on the SCG histomorphometrical changes and the protective effect of curcumin in preventing these changes. METHODS: Thirty-six male rats were randomly assigned to the control, curcumin, CSD, CSD + curcumin, grid floor control, and grid floor + curcumin groups. The CSD was induced by a modified multiple platform apparatus for 21 days and animals were sacrificed at the end of CSD or treatment, and their SCGs removed for stereological and TUNEL evaluations and also spatial arrangement of neurons in this structure. RESULTS: Concerning stereological findings, CSD significantly reduced the volume of SCG and its total number of neurons and satellite glial cells in comparison with the control animals ( P < 0.05). Treatment of CSD with curcumin prevented these decreases. Furthermore, TUNEL evaluation showed significant apoptosis in the SCG cells in the CSD group, and treatment with curcumin significantly decreased this apoptosis ( P < 0.01). This decrease in apoptosis was observed in all control groups that received curcumin. CSD also changed the spatial arrangement of ganglionic neurons into a random pattern, whereas treatment with curcumin preserved its regular pattern. CONCLUSIONS: CSD could potentially induce neuronal loss and structural changes including random spatial distribution in the SCG neurons. Deleterious effects of sleep deprivation could be prevented by the oral administration of curcumin. Furthermore, the consumption of curcumin in a healthy person might lead to a reduction of cell death.
Subject(s)
Animals , Male , Rats , Sleep Deprivation/pathology , Sleep Deprivation/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Superior Cervical Ganglion/drug effects , Curcumin/pharmacology , Rats, Sprague-DawleyABSTRACT
Objective To investigate the changes of myosin heavy chain ( MyHC) isoforms in rat masseter muscle fibers caused by chronic sleep deprivation ( CSD) and a possible link with the pathogenesis of temporomandibular joint disorders ( TMD ) .Methods Total 180 male rats were randomly divided into three groups( n=60 per group): chronic sleep deprivation group ( CSD),cage control group ( CC),and large-platform control group ( TC ) .Each group was further divided into three subgroups ( n=20 in each group)according to the observation time point(7,14,and 21 days).The expression of MyHC isoforms in mas-seter muscle fibers was investigated by real-time quantitative PCR,Western blotting and immunohistochemi-cal staining.Results The expression of MyHC-Ⅰ,MyHC-ⅡA and MyHC-ⅡB deep and shallow masseter muscle in CSD7d group had differention with the control group(MyHC-Ⅰ:(0.314±0.005,0.134±0.005, P0.05) ,and there were no differences between the CC and TC groups at any time point.Conclusion These findings suggest that CSD alters the ex-pression of MyHC isoforms,which may contribute to TMD pathogenesis.
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Con el objetivo de evaluar el efecto de la privación crónica de sueño sobre la presión arterial sistólica, se estudiaron 3 grupos de 8 ratas Wistar, un grupo control: sin privación de sueño y dos grupos experimentales: privación del sueño total y privación de fase de sueño MOR, durante períodos de 96 h continuas semanales, sin interrupción a lo largo de 2 meses. A dichos grupos se les midió la presión arterial sistólica cada semana antes de iniciar el período de privación de sueño. Al concluir los 2 meses, se les realizó extracción de ambos riñones. Los resultados revelaron que hubo diferencia estadísticamente significativa a partir de la semana 6 entre el grupo control y el grupo con privación del sueño total. En cuanto al estudio histológico de los cortes de los riñones, no se encontró alteración alguna de nefroesclerosis. En el modelo de estudio, la privación de sueño total produce un aumento notable de la presión arterial sistólica, no siendo así en el grupo con privación de fase de sueño MOR. Las alteraciones morfológicas renales no parecen participar en la hipertensión obtenida mediante las técnicas aplicadas.
With the objective of evaluating the effects of chronic sleep deprivation on the systolic blood pressure, three groups of 8 Wistar rats were studied- a control group with no sleep deprivation and two experimental groups subjected to total sleep deprivation and MOR sleep phase deprivation, respectively- for continuous 96h periods weekly throughout 2 months. Systolic blood pressure was taken in all the three groups every week before starting the sleep deprivation period. After two months, their kidneys were extracted. The results yielded that there was a statistically significant difference between the control group and the group subjected to total sleep deprivation. As to the histological study of the kidney cuts, nephrosclerosis alterations were not found. In the study model the total sleep deprivation brings about a remarkable rise in systolic blood pressure, except for the group which underwent MOR sleep phase deprivation and that renal morphological alterations does not seem to be involved in hypertension resulting from the applied techniques.