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Objective:To investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on learning-memory and the expression of synaptic plasticity proteins in hippocampus of rats with post-stroke sleep deprivation.Methods:A total of 28 SPF grade healthy male Wistar rats with 8-week old were randomly divided into four groups (control group, sham operation group, model group and rTMS group) according to random number table method, with 7 rats in each group. The rats in the model group and the rTMS group were treated with middle cerebral artery occlusion and p-chlorophenylalanine intraperitoneal injection to establish the post-stroke sleep deprivation model. The rats in the rTMS group were treated with rTMS intervention for consecutive 14 days after modeling. The rats in the sham operation group were only separated arteries but not ligated and inserted. The rats in control group were fed normally. The open field test (OFT) was used to observe the autonomous behavior of rats.The water maze test(WMT) was used to observe the spatial learning and memory ability of rats.The content of tyrosine kinase receptor type B(TrkB) in hippocampus was detected by Western blot.The expressions of brain-derived neurotrophic factor(BDNF) and immediate early gene c-fos in hippocampus were detected by immunofluorescence.The morphology and structure of neurons in hippocampus were observed by optical microscopy and transmission electron microscopy. SPSS 21.0 software was used for statistical analysis, and repeated measurement ANOVA was used for the escape latency data, one-way ANOVA was used for the comparison of other data among multiple groups, and LSD test was used for further pairwise comparison.Results:(1) The OFT results showed that there were statistical differences in the numbers of crossing squares, upright times and total points of rats in the four groups after intervention ( F=27.638, 10.425, 30.690, all P<0.001). The numbers of crossing squares ((72.71±10.10)), upright times ((6.57±0.87)times) and total points ((79.29±10.03) points) of rats in rTMS group were all higher than those in model group after intervention ((43.71±6.96), (3.43±0.65)times, (47.14±6.82)points) (all P<0.05). As for the escape latency of WMT among the four groups of rats, the interaction effect was not significant( F=1.108, P=0.37), and the time main effect( Ftime=27.295, Ptime<0.01) and group main effect ( Fgroup=8.691, Pgroup<0.01) were significant after rTMS intervention.On the 3rd and 4th day, the escape latency of rTMS group rats was lower than that of the model group (both P<0.01). There were statistically significant differences in the numbers of crossing platform, swimming distance and residence time in target quadrant of rats in the four groups after intervention( F=8.569, 3.308, 3.547, all P<0.05). The numbers of crossing platform ((2.00±0.31)times), swimming distance in target quadrant ((196.95±24.57) cm) and residence time ((17.72±1.36)s) of rats in rTMS group were all higher than those in model group after intervention ((1.57±0.30)times, (146.61±4.79) cm, (13.58±0.98)s)(all P<0.05). (2)Optical microscopy and transmission electron microscopy showed that the hippocampal cells arranged irregularly, the organelles' integrity was destroyed in the model group compared with the normal control group. In rTMS group the arrangement and structure of nerve cells in the hippocampus were improved after rTMS intervention. (3) The immunofluorescence results showed that c-fos (1.49±0.09) and BDNF (0.84±0.06) in the hippocampus of rats in rTMS group were both higher than those in model group ((1.24±0.12), (0.48±0.08))(both P<0.05). The Western blot results showed that the expression level of TrkB (1.81±0.03) in the hippocampus of rats in rTMS group was higher than that in model group (0.96±0.02) ( P<0.05). Conclusion:The rTMS can improve the learning-memory ability and autonomous capacity of rats with post-stroke sleep deprivation, which may be related to promoting the expression of c-fos, BDNF and TrkB in hippocampus tissue.
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Objective:To evaluate the effect of sleep deprivation on the expression of sirtuin 6 (SIRT6) in the cerebellum of immature mice.Methods:Fifty SPF healthy male C57BL/6 mice, aged 4 weeks, weighing 14-16 g, were divided into 2 groups ( n=25 each) using a random number table method: control group (Con group) and sleep deprivation group (SD group). The chronic sleep deprivation model was prepared by using the multi-platform water environment method, with 20 h of sleep deprivation per day for 10 consecutive days. After sleep deprivation, a balance beam experiment was performed to test the balance and coordination ability of mice. The mice were sacrificed after anesthesia and cerebellar lobular IV-VI (4-6 cb) tissues were taken for microscopic examination of the ultrastructure (with a transmission electron microscope) and for determination of the dendritic spine density of cerebellar 4-6cb Purkinje neurons (by Golgi staining), co-expression of SIRT6 and Calbindin D-28k (CbD-28k) and expression of glucose transporter Glut3 of cerebellar 4-6cb (by immunofluorescence staining). Results:Compared with group Con, the duration of passage through the balance beam was significantly prolonged, and the number of posterior foot slips was increased, the synaptic gap of cerebellar 4-6cb neurons was increased, the thickness of postsynaptic density was increased, the density of dendritic spines of Purkinje cells and the number of positive cells co-expressing SIRT6 and CbD-28k were decreased, and the expression of Glut3 was down-regulated in group SD ( P<0.05). Conclusions:The mechanism by which sleep deprivation decreases the abilities of balance and coordination is related to down-regulating SIRT6 expression in cerebellar Purkinje cells and decreasing neuronal glucose metabolism, thus damaging the synaptic plasticity of cerebellum in immature mice.
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Objective:To evaluate the role of cancerous inhibitor of protein phosphatase 2A (CIP2A) in preoperative sleep deprivation (PSD)-induced aggravation of postoperative cognitive dysfunction (POCD) in aged mice.Methods:One hundred and ten healthy C57BL/6J mice of either sex, aged 18-20 months, weighing 29-35 g, were divided into 5 groups ( n=22 each) using a random number table method: sham operation group (S group), abdominal surgery group (O group), PSD + abdominal surgery group (D+ O group), CIP2A shRNA + abdominal surgery group (CS+ O group), and CIP2A shRNA+ PSD+ abdominal surgery group (CS+ D+ O group). At 14 days before surgery, control shRNA lentivirus was injected into the hippocampus in S, O and CS+ O groups, and CIP2A shRNA was injected into the hippocampus in D+ O and CS+ D+ O groups. PSD was carried out for 3 consecutive days prior to surgery. Cognitive function was assessed using the Morris water maze test at days 7-11 after surgery. The mice were sacrificed under deep anesthesia at day 3 after surgery, and hippocampal tissues were obtained to determine the expression of CIP2A, high mobility group box 1 (HMGB1), ionized calcium-binding adapter molecule 1 (Iba-1), alpha subunit of protein phosphatase 2A (PP2Aa), catalytic subunit of protein phosphatase 2A (PP2Ac), phosphorylated tau protein (p-tau) (S396), and p-tau (S404) (by Western blot), levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD), and count of Iba-1 positive cells in the hippocampal CA1 region (using immunofluorescence staining). Results:Compared with S group, the escape latency was significantly prolonged, the frequency of crossing the platform was reduced, duration of stay in the target quadrant was shortened, the expression of CIP2A, Iba-1 and HMGB1 was up-regulated, PP2Ac expression was down-regulated, levels of ROS and MDA and count of Iba-1 positive cells were increased, and the activity of SOD was decreased in O group ( P<0.05). Compared with O group, the escape latency was significantly prolonged, the frequency of crossing the platform was reduced, duration of stay in the target quadrant was shortened, the expression of CIP2A, Iba-1 and HMGB1 was up-regulated, PP2Ac expression was down-regulated, levels of ROS and MDA and count of Iba-1 positive cells were increased, and the activity of SOD was decreased in D+ O group, and the escape latency was significantly shortened, the frequency of crossing the platform was increased, duration of stay in the target quadrant was prolonged, the expression of CIP2A, Iba-1 and HMGB1 was down-regulated, PP2Ac expression was up-regulated, levels of ROS and MDA and count of Iba-1 positive cells were decreased, and the activity of SOD was increased in CS+ O group ( P<0.05). Compared with D+ O group, the escape latency was significantly shortened, the frequency of crossing the platform was increased, duration of stay in the target quadrant was prolonged, the expression of CIP2A, Iba-1 and HMGB1 was down-regulated, PP2Ac expression was up-regulated, levels of ROS and MDA and count of Iba-1 positive cells were decreased, and the activity of SOD was increased in CS+ D+ O group ( P<0.05). There was no significant difference in PP2Aa expression among the five groups ( P>0.05). Conclusions:The mechanism by which PSD aggravates POCD is related to up-regulating the expression of CIP2A and promoting oxidative stress responses, neuroinflammatory responses and phosphorylation of tau protein in aged mice.
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Objective:To evaluate the effect of propofol on parvalbumin (PV) neurons in the medical prefrontal cortex(mPFC)of rats with social behavior disorders induced by chronic sleep deprivation.Methods:Forty-two SPF male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 3 groups ( n=14 each) using a random number table method: control group (group Con), chronic sleep deprivation plus natural sleep group (group CSD+ NS), and chronic sleep deprivation plus propofol group (group CSD+ Pro). Sleep deprivation model was established by the modified multiple platform method, the rats were placed in the sleep-deprivation tank for 20 h a day (14: 00-10: 00), and allowed to sleep naturally for 4 h (10: 00-14: 00) a day for 28 consecutive days. Propofol 40 mg/kg was intraperitoneally injected for 28 consecutive days after sleep deprivation in CSD+ Pro group. While the equal volume of 10% fat emulsion was given in Con and CSD+ NS groups. After the end of sleep deprivation, a three-box social experiment was used to detect the social behavior of rats, and the number of the PV positive cells and density of the perineuronal network (PNN) in the mPFC area were measured by immunofluorescence. Results:Compared with group Con, the pertentage of rapid eye movement sleep and sniffing time preference coefficients for the strange rat 1 in the first stage and for the strange rat 2 in the second stage were significantly decreased, and the number of the PV positive cells and density of PNN in the mPFC area were decreased in group CSD+ NS ( P<0.05). Compared with group CSD+ NS, the sniffing time preference coefficients for the strange rat 1 in the first stage and for the strange rat 2 in the second stage were significantly increased, the number of the PV positive cells and density of PNN in the mPFC area were increased( P<0.05), and no significant change was found in the percentage of the rapid eye movement sleep in group CSD+ Pro. Conclusions:Propofol probably increases the number and function of PV neurons in the mPFC and ameliorates sleep deprivation-induced social behavior disorders in sleep-deprived rats.
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Sleep deprivation refers to the loss of sleep caused by self-inflicted or external factors. There is increasing evidence that pregnancy is prone to sleep deprivation, which not only disrupts maternal functions but also affects offspring′s cognitive function. This article reviews the effects of sleep deprivation during pregnancy on offspring cognition and its underlying mechanisms, in order to establish a foundation for developing scientifically sound sleep strategies during pregnancy and to provide clinical insights for improving the neurodevelopment and cognitive function of offspring.
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ObjectiveTo observe the effect of modified Tianwang Buxindan （MTBD） on the skin of sleep-deprived （SD） mice and investigate its mechanism. MethodSixty 2-month-old female Kunming mice were randomly divided into a blank group， a model group， a vitamin C （VC， 0.08 g·kg-1）， and MTBD low-， medium-， and high-dose groups （6.5， 12.5， 25 g·kg-1）. Except for the blank group， the other groups were subjected to SD mouse model induction （using multiple platform water environment method for 18 hours of sleep deprivation daily from 15：00 to next day 9：00）， continuously for 14 days， and caffeine （CAF， 7.5 mg·kg-1） was injected intraperitoneally from the 2nd week onwards， continuously for 7 days. While modeling， the blank group and the model group were administered with normal saline （0.01 mL·g-1）， and the other groups received corresponding drugs for treatment. On the day of the experiment， general observations were recorded （such as body weight， spirit， fur， and skin）. After sampling， skin tissue pathological changes were observed under an optical microscope using hematoxylin-eosin （HE） and Masson staining methods. Skin thickness and skin moisture content were measured. Biochemical assay kits were used to detect skin hydroxyproline （HYP） content， skin and serum superoxide dismutase （SOD） activity， and malondialdehyde （MDA） content. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum interleukin （IL）-6， tumor necrosis factor （TNF）-α， and IL-1β levels in mice. Western blot was used to detect skin tissue type Ⅰ collagen （ColⅠ）， type Ⅲ collagen （ColⅢ）， phosphatidylinositol 3-kinase （PI3K）， phosphorylated （p）-PI3K， protein kinase B （Akt）， p-Akt， nuclear factor E2-related factor 2 （Nrf2）， heme oxygenase （HO）-1， and nuclear factor （NF）-κB protein expression. ResultCompared with the blank group， the model group showed varying degrees of changes. In general， signs of aging such as reduced body weight （P<0.01）， listlessness， dull fur color， and formation of wrinkles on the skin appeared. Tissue specimen testing revealed skin thinning， flattening of the dermoepidermal junction （DEJ）， and reduced collagen fibers under the optical microscope. Skin thickness and moisture content decreased， skin tissue HYP content significantly decreased （P<0.01）， skin and serum SOD activity significantly decreased （P<0.01）， and MDA content significantly increased （P<0.01）. Serum IL-6， TNF-α， and IL-1β levels significantly increased （P<0.01）. Skin ColⅠ， ColⅢ， p-PI3K/PI3K， p-Akt/Akt， Nrf2， and HO-1 protein expression significantly decreased （P<0.05， P<0.01）， and NF-κB expression increased （P<0.01）. Compared with the model group， the VC group and the MTBD low-dose group showed increased skin moisture content， HYP content， SOD activity， and ColⅠ， ColⅢ， p-PI3K/PI3K protein expression （P<0.05， P<0.01）， and decreased serum MDA content （P<0.05）. In addition， a decrease in serum IL-6 and IL-1β levels was detected in the MTBD low-dose group （P<0.05）， while the above indicators in the MTBD medium- and high-dose groups improved （P<0.05， P<0.01）. ConclusionSleep deprivation accelerates the aging process of the skin in SD model mice. MTBD can improve this phenomenon， exerting anti-inflammatory and antioxidant effects， and its mechanism of action may be related to the activation of the PI3K/Akt/Nrf2 signaling pathway.
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Inner ear diseases are common in the field of otolaryngology,including hearing loss,tinnitus and peripheral vestibular dysfunction.Their pathogenesis is relatively complex,which is one of the hot spots in current research.A large number of studies have demonstrated that sleep disorder is an important inducement of inner ear diseases.This paper reviews the impact of sleep deprivation on inner ear diseases in order to pro-vide a theoretical basis for the mechanisms of sleep deprivation on inner ear diseases.
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Abstract Objective: The aim of this study was to investigate the association between iron deficiency anemia and sleep duration in the first year of life. Methods: A total of 123 infants were investigated, with sleep being evaluated at 3, 6, and 12 months of age and anemia at birth and 6 months. The cutoff points for anemia and short sleep duration were hemoglobin <11 g/dL (at birth and/or 6 months) and <10 h (at 3, 6, and 12 months), respectively. The comparison of the average sleep time between infants with and without anemia was performed using the Student's t-test, and logistic regression models were also used to verify differences in the sleep duration (short/not short) between the groups. Linear regression analyses were conducted to determine the association between sleep duration and hemoglobin values. The analyses were adjusted for potential confounders. Results: Children with anemia were more likely to be short sleepers [odds ratio (95% confidence interval (CI)): 4.02 (1.02-15.76); p≤0.05], and for each unit increase in hemoglobin values, the sleep duration increased by 16.2 min [β (95%CI): 0.27 (0.00-0.55); p≤0.05), regardless of family income, maternal schooling, gender, and body mass index at birth. Conclusions: Our results suggest that iron deficiency anemia is associated with short sleep duration in the first year of life and indicate the need for longitudinal investigations, with longer follow-up, to verify the impact of anemia on sleep duration at subsequent ages.
RESUMO Objetivo: Investigar a associação entre a anemia por deficiência de ferro e a duração do sono no primeiro ano de vida. Métodos: Foram avaliadas 123 crianças, sendo o sono investigado aos três, seis e 12 meses de idade e a anemia ao nascimento e aos seis meses. Utilizaram-se como pontos de corte para anemia e curta duração de sono, respectivamente, hemoglobina<11 g/dL (nascimento e/ou seis meses) e tempo total <10 h (3, 6 e/ou 12 meses). A comparação do tempo médio de sono entre as crianças com e sem anemia foi realizada pelo teste t de Student e modelos de regressão logística foram usados para verificar diferenças na duração do sono (curta/não curta) entre os grupos. Análises de regressão linear foram conduzidas para determinar a associação entre a duração do sono e valores de hemoglobina. As análises foram ajustadas para potenciais confundidores. Resultados: As crianças com anemia tiveram maior chance de apresentar curta duração do sono [odds ratio — OR (intervalo de confiança — IC95%): 4,02 (1,02-15,76); p≤0,05]. Para cada unidade de aumento nos valores da hemoglobina, o tempo de sono aumentou em 16,2 min [β (IC95%): 0,27 (0,00-0,55); p≤0,05), independentemente de renda familiar, escolaridade materna, sexo e índice de massa corporal ao nascimento. Conclusões: Nossos resultados sugerem que a anemia ferropriva está associada à curta duração do sono no primeiro ano de vida e indicam a necessidade de investigações longitudinais, com maior tempo de seguimento, para verificar o impacto da anemia na duração do sono em idades subsequentes.
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ABSTRACT Objective: To investigate the association between sleep duration, nocturnal awakenings, and sleep latency with body mass index (BMI) at six and 12 months of age. Methods: 179 children from a birth cohort were enrolled. At six and 12 months of age, anthropometric data were obtained using standardized techniques and infants' mothers answered the Brief Infant Sleep Questionnaire for sleep data. The association of BMI with the independent variables (sleep duration, latency, and nocturnal awakenings) was assessed by linear regression models. Analyses were adjusted for potential confounders and a p-value<0.05 was adopted to define statistical significance. Results: For each additional hour of sleep duration, BMI was reduced by 0.15 kg/m² (95% confidence interval [CI] -0.28; -0.01; p=0.03) and each additional minute of sleep latency increased BMI by 0.01 kg/m² (95%CI -0.00; 0.03; p=0.02). These associations were independent of gestational age, child sex, birth weight, duration of exclusive breastfeeding, smoking during pregnancy, and mother's BMI, education, and marital status. Nocturnal awakenings showed no association with the outcome. Conclusions: Our findings suggest that sleep duration and sleep latency time are associated with BMI in the first year of life. Insights into the influence of sleep early in life on weight status may be helpful to complement future nutritional recommendations and prevent and treat obesity.
RESUMO Objetivo: Investigar a associação entre duração do sono, despertares noturnos e latência do sono com o índice de massa corporal (IMC) aos seis e 12 meses de idade. Métodos: foram incluídas 179 crianças de uma coorte de nascimentos. Aos seis e 12 meses de idade, dados antropométricos foram obtidos por meio de técnicas padronizadas e as mães dos lactentes responderam ao Brief Infant Sleep Questionnaire para dados do sono. A associação do IMC com as variáveis independentes (duração do sono, latência e despertares noturnos) foi avaliada por modelos de regressão linear. As análises foram ajustadas para potenciais fatores de confusão e o p-valor<0,05 foi adotado para definir a significância estatística. Resultados: Para cada hora adicional de duração do sono, o IMC foi reduzido em 0,15 kg/m² (intervalo de confiança [IC]95% -0,28; -0,01; p=0,03) e cada minuto adicional no tempo de latência resultou em aumento de 0,01 kg/m² (IC95% -0,00; 0,03; p=0,02) no IMC. Essas associações foram independentes da idade gestacional, sexo da criança, peso ao nascer, duração do aleitamento materno exclusivo, tabagismo durante a gravidez e IMC, escolaridade e estado civil da mãe. Os despertares noturnos não apresentaram associação com o desfecho. Conclusões: Nossos achados sugerem que a duração e a latência do sono estão associadas ao IMC no primeiro ano de vida. Informações sobre a influência do sono no início da vida sobre o status do peso podem ser úteis para complementar futuras recomendações nutricionais e prevenir e tratar a obesidade.
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O objetivo do estudo foi avaliar a qualidade do sono e sonolência diurna de um grupo de idosos, verificar se há associação com prática de atividade física, presença de doença crônica, e Índice de Massa Corporal (IMC) e se há correlação com IMC, idade e qualidade de vida. Trata-se de um estudo transversal e descritivo. Para avaliação da qualidade do sono utilizou-se o Pittsburgh Sleep Quality Index (PSQI), para avaliação da sonolência diurna a Escala de Sonolência de Epworth (ESE) e para avaliação da qualidade de vida o WHOQOL-BREF. Foram avaliados 47 idosos com mediana (intervalo interquartil 25-75%) de 66 (62-70) anos de idade e IMC de 28,58 (26,21-30,44). 74,5% apresentaram sono ruim, 61,7% apresentaram Sonolência Diurna Normal e 97,8% classificados com boa qualidade de vida, com destaque para os domínios relações sociais (80%) e autoavaliação da qualidade de vida (80%). Apenas apresentou associação estatisticamente significativa a presença de qualidade de sono ruim com a prática de atividade física. Não houve associação entre presença de qualidade de sono ruim ou sonolência com IMC e presença de doença crônica. Houve uma correlação fraca, negativa e estatisticamente significativa apenas entre qualidade do sono com qualidade de vida (ρ=-0,466) e idade (ρ=-0,297). Conclui-se que os idosos apresentaram qualidade do sono ruim, sonolência diurna normal e qualidade de vida geral boa.
The objective of the study was to evaluate the quality of sleep and daytime sleepiness of a group of elderly people, checking whether there is an association with physical activity, presence of chronic disease, and Body Mass Index (BMI) and whether there is a correlation with BMI, age and quality of life. This is a cross-sectional and descriptive study. To assess sleep quality, the Pittsburgh Sleep Quality Index (PSQI) was used, the Epworth Sleepiness Scale (ESE) was used to assess daytime sleepiness, and the WHOQOL-BREF was used to assess quality of life. 47 elderly people were evaluated with a median (interquartile range 25-75%) of 66 (62-70) years of age and BMI of 28.58 (26.21-30.44). 74.5% had poor sleep, 61.7% had Normal Daytime Sleepiness and 97.8% classified as having a good quality of life, with emphasis on the domains of social relationships (80%) and self-assessment of quality of life (80%). There was only a statistically significant association between the presence of poor sleep quality and the practice of physical activity. There was no association between the presence of poor sleep quality or sleepiness with BMI and the presence of chronic disease. There was a weak, negative and statistically significant correlation only between sleep quality and quality of life (ρ=-0.466) and age (ρ=- 0.297). It is concluded that the elderly had poor sleep quality, normal daytime sleepiness and good general quality of life.
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Introduction: The COVID?19 pandemic took the entire world unawares and people were forced to stay indoors overnight. Due to this a drastic change ensued in lifestyle with many succumbing to various kinds of stresses and psychological problems. This study aims to study the changing sleep patterns and level of anxiety among the working population due to the COVID?19 Pandemic lockdown. Methodology: An online survey was conducted using a cloud?based website. The sleep patterns both prior to and during the lockdown period of the pandemic were assessed using a self?administered questionnaire. The level of anxiety during both these periods (before and during lockdown) amongst the working population was also assessed using the Generalized Anxiety Disorder Scores (GADS). Results: A total of 224 individuals participated in the study of which 52.7% were males and 47.3% were females. On analysis, the lifestyle and sleep deprivation scores showed that before the lockdown only 2.7% reported a low score out of total participants. However, this number was raised to 13.4% during the lockdown. The percentage of people reporting deteriorated sleep quality gradually increased with females reporting moderate to severe category of Generalized Anxiety Disorder scores as compared to Males. Conclusion: The study suggests that there has been a significant change in the sleep quality of the study participants due to Covid enforced lockdown which if unnoticed might lead to significant health problems. The effective use of programs like yoga, meditation, and deep breathing exercises, if followed timely could reduce psychological distress to some extent.
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Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor (CB1R) could affect novel object recognition (NOR) memory in chronically rapid eye movement sleep-deprived (RSD) rats.Methods The animals were examined for recognition memory following a 7-day chronic partial RSD paradigm using the multiple platform technique. The CB1R antagonist rimonabant (1 or 3 mg/kg, i.p.) was administered either at one hour prior to the sample phase for acquisition, or immediately after the sample phase for consolidation, or at one hour before the test phase for retrieval of NOR memory. For the reconsolidation task, rimonabant was administered immediately after the second sample phase.Results The RSD episode impaired acquisition, consolidation, and retrieval, but it did not affect the reconsolidation of NOR memory. Rimonabant administration did not affect acquisition, consolidation, and reconsolidation; however, it attenuated impairment of the retrieval of NOR memory induced by chronic RSD.Conclusions These findings, along with our previous report, would seem to suggest that RSD may affect different phases of recognition memory based on its duration. Importantly, it seems that the CB1R may, at least in part, be involved in the adverse effects of chronic RSD on the retrieval, but not in the acquisition, consolidation, and reconsolidation, of NOR memory.
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Rats , Animaux , Rimonabant/pharmacologie , Mémoire , Sommeil paradoxal , Récepteurs de cannabinoïdes , Cannabinoïdes/pharmacologieRÉSUMÉ
Sleep occupies one-third of a person's lifetime and is a necessary condition for maintaining physiological function and health. With the increase in social and economic pressures, the growing use of electronic devices and the accelerated aging process of the population, insufficient sleep and its hazards have drawn widespread attention from researchers in China and abroad. Sleep deprivation refers to a decrease in sleep or a severe lack of sleep due to various reasons. Previous studies have found that sleep deprivation can cause extensive damage to the body, including an increased incidence and mortality rate of neuropathic diseases in the brain, cardiovascular diseases, imbalances in the gut microbiota, and other multi-organ diseases. The mechanisms underlying the occurrence of multi-system and multi-organ diseases due to sleep deprivation mainly involve oxidative stress, inflammatory responses, and impaired immune function in the body. According to traditional Chinese medicine(TCM), sleep deprivation falls into the category of sleepiness, and long-term sleepiness leads to Yin-Yang imbalance, resulting in the consumption of Qi and damage to the five Zang-organs. The appropriate treatment should focus on tonifying deficiency, reinforcing healthy Qi, and harmonizing Yin and Yang. TCM is characterized by a wide variety and abundant resources, and it has minimal side effects and a broad range of applications. Numerous studies have shown that TCM drugs and prescriptions not only improve sleep but also have beneficial effects on liver nourishment, intelligence enhancement, and kidney tonification, effectively preventing and treating the body injury caused by sleep deprivation. Given the increasing prevalence of sleep deprivation and its significant impact on body health, this article reviewed sleep deprivation-mediated body injury and its mechanism, summarized and categorized TCM compound prescriptions and single drugs for preventing and treating body injury, with the aim of laying the foundation for researchers to develop effective drugs for preventing and treating body injury caused by sleep deprivation and providing references for further exploration of the molecular mechanisms underlying the body injury caused by sleep deprivation.
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Humains , Médecine traditionnelle chinoise , Privation de sommeil/traitement médicamenteux , Envie de dormir , Yin-yang , Chine , Médicaments issus de plantes chinoises/usage thérapeutiqueRÉSUMÉ
Objective The incidence of coronary microvascular disease(CMVD)is increasing annually.According to traditional Chinese medicine(TCM),CMVD belongs to the category of"collaterals",and qi deficiency and blood stasis are the main syndrome type of CMVD.Notably however,no studies have reported on the use of animal models of CMVD with qi deficiency and blood stasis.The current study therefore aimed to establish and evaluate a rat model of CMVD with qi deficiency and blood stasis syndrome.Methods Forty-five male SD rats were divided randomly into sham group,CMVD group,and CMVD + QXXY group(n = 15 rats per group).Rats in the CMVD + QXXY group were randomly deprived of sleep for 14～16 h/day for 6 weeks,and the model of qi deficiency syndrome was established.Animals in the sham group and the CMVD group were fed normally for 6 weeks.After 6 weeks,rats in the CMVD and CMVD + QXXY groups were anesthetized,their chests were opened,and embolic microspheres(40～120 μm)were injected into the left ventricle.Rats in the sham group underwent thoracotomy without injection of embolic microspheres.On day 7 after operation,relevant detection indicators were measured in each group.Results Compared with the sham group,the CMVD group showed a significant decrease in left ventricular ejection fraction and left ventricular shortening rate,while the activities of creatine kinase MB isoenzyme(CK-MB)and lactate dehydrogenase(LDH)were significantly increased.Heart function,hemorheology,myocardial enzyme index,and the degree of myocardial cell damage differed significantly between the CMVD + QXXY group compared with the sham group.Conclusions A rat model of CMVD + qi deficiency + blood stasis syndrome can be successfully established by sleep deprivation combined with intraventricular injection of embolic microspheres.This model will be suitable for the study of the pathogenesis of CMVD and the mechanisms of TCM.
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Objective Observe the effect of Liuwei Anshen Capsule on sleep improvement of aged sleep deprivation zebrafish model.Methods Sixty 18-month-old female zebrafish were randomly divided into blank group,model group,Liuwei Anshen group,and melatonin group.The zebrafish in the blank group were raised under normal lighting conditions,and the other three groups were constructed with continuous lighting for 3 days.Zebrafish in Liuwei Anshen group were treated with Liuwei Anshen capsule water solution 0.000 50 mg·mL-1 for 3 days on the basis of model group,and zebrafish in melatonin group were treated with melatonin aqueous solution 0.2 mg·mL-1 on the basis of model group for 3 days.After 3 days,the zebrafish behavior system was used to detect the resting time of zebrafish in each group.qRT-PCR method was used to detect cyclin 1a(per1a),cyclin2(per2),circadian motor output cycle 1a(clock1a),cryptochrome 1b(cry1b),and 5-hydroxyindoleacetic acid(5-htiaa)in each group of zebrafish and follicle-stimulating hormone beta(fshβ)gene expression levels.Western blot was used to detect the expression levels of estrogen receptorα(Esrα),Fshβand luteinizing hormone(Lh)in zebrafish in each group.HE staining was used to observe the ovary of zebrafish in each group.Results Compared with the zebrafish in the blank group,the resting time of the zebrafish in the model group decreased significantly(P<0.01)during the 24 hours of observation.After the intervention of Liuwei Anshen Capsule and melatonin,the resting time of the zebrafish was significantly increased.(P<0.01).Compared with the zebrafish in the blank group,the mRNA expressions of zebrafish circadian clock genes per1a,per2,clock1a,cry1b,5-htiaa,and fshβ all showed a downward trend after sleep deprivation(P<0.05,P<0.01).After the intervention of Liuwei Anshen Capsules,the mRNA expressions of per1,clock1a,cry1b,5-htiaa and fshβ were all up-regulated(P<0.05,P<0.01).Compared with the zebrafish in the blank group,the protein expressions of Esrα and Lh in the zebrafish of the model group were up-regulated(P<0.05),the expression of Fshβ protein was down-regulated(P<0.05),after the intervention of Liuwei Anshen Capsules,the above proteins did not change significantly.The ovarian tissue cells of the zebrafish in the blank group had normal morphology and a large number of primary oocytes,while the ovarian tissue cells of the zebrafish in the model group were damaged in morphology and the number of primary oocytes decreased,after the intervention of Liuwei Anshen Capsule and melatonin,the cell morphology of zebrafish ovarian tissue was still damaged to varying degrees,but the whole was relatively intact,and the number of primary oocytes increased.Conclusion The insomnia of aged zebrafish may be caused by multiple factors.Liuwei Anshen capsule has significant effects on estrogen level of rhythm gene and ovarian function of sleep-deprived aged zebrafish.
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Objective:To evaluate the effect of sleep deprivation on cognitive function in septic rats and its relationship with neuronal glycolysis isoenzyme phosphofructokinase-2/fructose-2,?6-diphosphatase 3 (PFKFB3).Methods:Fifty-six healthy male Sprague-Dawley (SD) rats were randomly divided into 4 groups ( n = 14): control group (Con group), sepsis group (LPS group), sepsis+sleep deprivation group (LPS+SD group), sepsis+sleep deprivation+glycolysis inhibitor 3-PO treatment group (LPS+SD+3-PO group). The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) 10 mg/kg. Rats in LPS+SD group were treated with sleep deprivation using a sleep deprivation instrument 24 hours after LPS injection. The LPS+SD+3-PO group was intraperitoneally injected with LPS for 24 hours, and then injected with 3-PO 50 mg/kg, followed by sleep deprivation. Novel object recognition experiments were performed 72 hours after LPS injection. Subsequently, blood and brain tissue samples were collected. The contents of lactate (Lac), reactive oxygen species (ROS) and serum tumor necrosis factor-α(TNF-α), neuron-specific enolase (NSE), pyruvate in brain tissue were detected by enzyme-linked immunosorbent assay (ELISA). Then, the lactate/pyruvate ratio was calculated. Na +-K +-ATPase activity in brain tissue was detected by colorimetry. Morphological changes in hippocampus were detected by hematoxylin-eosin (HE) staining. And the protein expression levels of PFKFB3, ZO-1 and cleaved caspase-3 were measured by Western blotting. Results:Compared with Con group, the novel object recognition index of LPS group was decreased, the levels of NSE, TNF-α, lactate/pyruvate ratio in serum and the levels of Lac, ROS and dry-wet weight ratio in brain tissue were significantly increased, Na +-K +-ATPase activity in brain tissue was decreased, the protein expressions of PFKFB3, caspase-3 were up-regulated, ZO-1 expression was down-regulated, and the neurons in hippocampus were slightly degenerated. Compared with LPS group, the novel object recognition index of LPS+SD group was further decreased [(39.4±5.3)% vs. (54.5±7.6)%)], serum NSE, TNF-α, lactate/pyruvate ratio and brain tissue Lac, ROS, dry-wet weight ratio were further increased [NSE (μg/L): 3.21±0.42 vs. 2.55±0.36, TNF-α (ng/L): 139.4±19.7 vs. 92.2±13.5, lactate/pyruvate ratio: 29.7±5.5 vs. 19.2±4.2, Lac (μmol/g): 19.51±2.33 vs. 11.34±1.52, ROS (kU/g): 117.4±18.7 vs. 78.2±11.8, dry-wet weight ratio: (81.3±9.2)% vs. (64.3±6.6)%], and Na +-K +-ATPase activity was further decreased (mmol·L -1·h -1: 1.88±0.34 vs. 2.91±0.39), the protein expressions of PFKFB3, caspase-3 were further up-regulated and ZO-1 expression was further down-regulated (PFKFB3/β-actin: 0.80±0.11 vs. 0.45±0.07, caspase-3/β-actin: 0.71±0.09 vs. 0.37±0.05, ZO-1/β-actin: 0.31±0.05 vs. 0.61±0.08). The differences were statistically significant (all P < 0.05). HE staining showed that the degeneration of neurons in hippocampus was significantly aggravated. Compared with LPS+SD group, the novel object recognition index of LPS+SD+3-PO group was increased [(50.8±5.9)% vs. (39.4±5.3)%], NSE, TNF-α, lactate/pyruvate ratio of serum and Lac, ROS, dry-wet weight ratio of brain tissue were significantly decreased [NSE (μg/L): 2.60±0.33 vs. 3.21±0.42, TNF-α (ng/L): 103.7±18.3 vs. 139.4±19.7, lactate/pyruvate ratio: 17.4±5.1 vs. 29.7±5.5, Lac (μmol/g): 13.68±2.02 vs. 19.51±2.33, ROS (kU/g): 86.9±14.5 vs. 117.4±18.7, dry-wet weight ratio: (67.7±6.9)% vs. (81.3±9.2)%], and Na +-K +-ATPase activity was increased (mmol·L -1·h -1: 2.82±0.44 vs. 1.88±0.34). The protein expressions of PFKFB3, caspase-3 were down-regulated and ZO-1 expression was up-regulated (PFKFB3/β-actin: 0.50±0.06 vs. 0.80±0.11, caspase-3/β-actin: 0.43±0.06 vs. 0.71±0.09, ZO-1/β-actin: 0.52±0.06 vs. 0.31±0.05). The differences were statistically significant (all P < 0.05). HE staining showed that the degeneration of neurons in hippocampus was significantly improved. Conclusions:Sleep deprivation could aggravate neuroinflammation, neuronal degeneration and apoptosis in septic rats, resulting in destruction of blood-brain barrier and cognitive impairment. 3-PO treatment significantly alleviate the injury and degeneration of hippocampal neurons in septic rats, inhibit neuroinflammation and apoptosis, and improve cognitive dysfunction, which may be related to the inhibition of glycolytic isoenzyme PFKFB3.
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Objective:To investigate the possible role and mechanism of purinergic ligand-gated ion channel 7(P2X7)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3) inflammasome pathway in cognitive impairment induced by sleep deprivation (SD)mice.Methods:SPF grade male C57BL / 6J mice aged 6-8 weeks were randomly divided into 3 groups according to the random number table method with 6 mice in each group.They were normal control group (CC group), SD group and SD+ P2X7 receptor antagonist brilliant blue G(BBG) group (SD+ BBG group). Modified multiple platform method was used to establish a 5-day SD model in mice.During the SD intervention period, the mice in SD+ BBG group were injected with BBG(50 mg/kg) intraperitoneally once a day, while the mice in CC group and SD group were injected with the same volume of 0.9% sodium chloride solution.Morris water maze was conducted to evaluate the cognitive function of mice.The protein expression levels of P2X7, NLRP3, caspase-1, apoptosis-associated proteins(ASC) and interleukin-1β(IL-1β) in hippocampus were detected by Western blot.RT-qPCR was used to detect the mRNA expression levels of tumor necrosis factor-α(TNF-α), IL-1β, interleukin-18(IL-18) and microglial polarization surface markers CD206 and CD86 in hippocampus.Graph pad Prism 8.0 software and SPSS 25.0 software were used for statistical analysis and mapping.Results:(1) The interaction effect between time and groups of escape latency in three groups of mice was significant ( F=15.76, P<0.001). From the 2nd to 5th day, the escape latencies of mice in SD group were higher than those of CC group, while the escape latencies of mice in SD+ BBG group were lower than those of SD group (all P<0.05). (2)The results of the space exploration experiment showed that there were statistically significant differences in target quadrant residence time and the times of crossing the platform( F=6.65, P=0.009; F=12.39, P<0.001). The target quadrant residence time ((23.42±0.55) s) and times of crossing the platform ((17.67±0.71) times) of the SD group were both lower than those of the CC group ((29.48±1.78) s, (23.33±0.95) times) (both P<0.05), while the target quadrant residence time ((28.62±1.19) s) and the times of crossing the platforms ((21.33±0.76) times) of the SD+ BBG group were both higher than those of the SD group (both P<0.05). (3)There were statistically significant differences in the protein levels of inflammatory related proteins such as P2X7, NLRP3, caspase-1, ASC and IL-1β in the hippocampus of mice among the 3 groups( F=8.23, 8.97, 8.45, 54.42, 8.12, all P<0.05). Compared with CC group, the protein levels of P2X7 ((0.93±0.02), (0.71±0.04)), NLRP3 ((0.97±0.04), (0.62±0.09)), caspase-1 ((1.00±0.03), (0.76±0.07)), ASC ((0.96±0.02), (0.77±0.04)) and IL-1β ((0.85±0.07), (0.54±0.04)) in SD group were all higher (all P<0.05). Compared with SD group, the protein levels of P2X7 (0.74±0.05), NLRP3 (0.78±0.02), caspase-1 (0.74±0.04), ASC (0.67±0.02), IL-1β (0.53±0.07) in SD+ BBG group were all lower (all P<0.05). (4)There were statistically significant differences in the mRNA levels of IL-18, IL-1β, TNF-α, CD86 and CD206 in hippocampus among the three groups ( F=12.80, 12.28, 105.80, 7.06, 30.19, all P<0.05). The mRNA levels of IL-18, IL-1β, TNF-α, CD86 in SD group were all higher than those in CC group(all P<0.05), while the mRNA level of CD206 in SD group was lower than that in CC group( P<0.05). Compared with SD group, the mRNA levels of IL-18, IL-1β, TNF-α, CD86 were lower in SD+ BBG group (all P<0.05), while the CD206 mRNA level of SD+ BBG group was higher than that in SD group( P<0.05). Conclusion:SD intervention can lead to cognitive impairment and increased expression of P2X7 in hippocampus of mice, which may be related to the activation of P2X7/ NLRP3 inflammasome signaling pathway, promoting the polarization of microglia into pro-inflammatory type and up-regulating the expression of pro-inflammatory cytokines.Inhibition of P2X7 can improve the cognitive function of mice.
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Sleep is essential for the maintenance of human normal functions.Nowadays,the occurrence of active sleep deprivation(ASD)or passive sleep depriva-tion(PSD)is becoming more and more common due to the inability of the body adapting to the rapid changes in the internal and external environment.SD is not only an action,a brief process or a result,but also a directly or indirectly sustained state,which is associated to sleep time,circadian rhythm or sleep quality.SD can lead to numerous adverse effects on the body,such as sleep-related acute and chronic diseases.Long-term SD increases the risk of neurological and cardiovascular dis-eases as well as immune system dysfunction.In addi-tion,SD may affect the reproductive health of the body,giving rise to a series of potential fertility problems.In recent years,the correlation research and mechanism between SD and the related diseases have become a focus of scholars' attention.Numerous lines of evidence suggest that pathological sleep,such as insomnia and sleep apnea syndrome,is associated with impaired repro-ductive function.Disruptions in the circadian rhythm can also lead to impaired hypothalamic-pituitary-gonadal(HPG)axis function and thereby interfere with the repro-ductive process.Our research team has demonstrated that SD significantly affects the fertility of male and female rats and has adverse effects on reproduction.By new generation sequencing(NGS)and RT-PCR verifica-tion,we have identified differently expressed genes that are involved in mediating the effect of SD on fertility.However,the mechanisms and biological macromolecules regulated by SD are worthy of being further explored.This paper provides a brief review of SD research and then focuses on the adverse impact of SD on fertility,conducting a literature review to sort out the ideas and pro-vide references for research in this field.
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Objective:To compare the effects of desflurane and sevoflurane anesthesia on the sleep quality of sleep-deprived mice.Methods:Thirty-two clean-grade healthy male C57BL/6 mice, aged 10 weeks, weighing 20-25 g, were divided into 4 groups ( n=8 each) by the random number table method: control group (C group), sleep deprivation group (SD group), sleep deprivation+ sevoflurane group (SD+ SEV group), and sleep deprivation+ desflurane group (SD+ DES group). In the four groups, EEG-EMG electrodes were implanted for recording EEG and EMG, and sleep deprivation model was developed by the gentle stimulation method with a brush for 12 h (6: 00-18: 00) after 7 days of adaptation. The 6 h after sleep deprivation was divided into 2 time periods: T 1 period (18: 00-20: 00) and T 2 period (20: 00-24: 00). T 1 period In SD group, mice were allowed ad libitum recovery sleep after sleep deprivation. C group and SD group were exposed to 60% oxygen 1.5 L/min. In SD+ DES group and SD+ SEV group, mice were exposed to 6% desflurane and 2.5% sevoflurane, respectively, for 2 h in 60% oxygen 1.5 L/min following sleep deprivation. T 2 period Four groups were allowed ad libitum recovery sleep with the EEG-EMG signal recording. The percentages and number of wakefulness time, rapid eye movement time and non-rapid eye movement time during each time period were calculated using Lunion Data software. Results:Compared with C group, the percentage of non-rapid eye movement time and the percentage of rapid eye movement time were significantly decreased, and the percentage of wakefulness time was increased during 12 h sleep deprivation in SD group, SD+ SEV group and SD+ DES group ( P<0.05). Compared with T 1 period, the percentage of non-rapid eye movement time was significantly increased, and the percentage of wakefulness time and percentage of rapid eye movement time were decreased in T 2 period in SD group ( P<0.05). Compared with SD group, the percentage of non-rapid eye movement time and percentage of rapid eye movement time were significantly decreased, and the percentage of wakefulness time was increased in T 2 period in SD+ SEV group and SD+ DES group ( P<0.05). There was no significant difference in the percentage of non-rapid eye movement, rapid eye movement and wakefulness time in T 2 period between SD+ SEV group and SD+ DES group ( P>0.05). Compared with SD+ SEV group, the number of non-rapid eye movement in T 2 period was significantly reduced in SD+ DES group ( P<0.05). Conclusions:The effect of desflurane anesthesia in improving sleep quality is better than sevoflurane anesthesia in sleep-deprived mice.
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Objective:To evaluate the role of Homer1a/metabotropic glutamate receptor 5 (mGluR5) signaling pathway in sleep deprivation-induced cognitive dysfunction in aged rats.Methods:One hundred and four SPF healthy male Sprague-Dawley rats, aged 22-24 months, weighing 320-360 g, were divided into 4 groups ( n=26 each) using a random number table method: normal control group (group Control), sleep deprivation+ vehicle group (group SD+ Vehicle), sleep deprivation+ mGluR5 forward allosteric agent CDPPB group (group SD+ CDPPB), and sleep deprivation+ mGluR5 antagonist MPEP group (group SD+ MPEP). A 48-h sleep deprivation model was developed by sleep-deprived rod method. At the beginning of developing the model and 24 h after developing the model, CDPPB 10 mg/kg, MPEP 10 mg/kg and the equal volume of 1% Tween 80 were intraperitoneally injected in group SD+ CDPPB, group SD+ MPEP and group SD+ Vehicle, respectively.Morris water maze and novel object recognition tests were conducted to evaluate cognitive function after development of the model. The expression of Homer1a and mGluR5 in the hippocampus was detected by Western blot, the dendritic spine density in the hippocampal CA1 region was detected by Golgi staining, and the field excitatory postsynaptic potential (fEPSP) slope in the hippocampal CA1 region was detected by isolated electrophysiology. Results:Compared with Control group, the number of crossing the original platform, time of staying at the target quadrant, and novel object recognition index at 1 and 24 h after training were significantly decreased, the expression of Homer1a in the hippocampus was up-regulated, the expression of mGluR5 in the hippocampus was down-regulated, and the density of dendritic spine and fEPSP slope in the hippocampal CA1 region were decreased in group SD+ Vehicle ( P<0.05). Compared with group SD+ Vehicle, the number of crossing the original platform, time of staying at target quadrant, and novel object recognition index at 1 and 24 h after training were significantly increased, the expression of mGluR5 in hippocampus was up-regulated, and the density of dendritic spines and fEPSP slope in the hippocampal CA1 region were increased in group SD+ MPEP( P<0.05), and no statistically significant change was found in the parameters mentioned above in group SD+ CDPPB ( P>0.05). Conclusions:Sleep deprivation impairs the synaptic plasticity of hippocampal neurons by regulating Homer1a/mGluR5 signaling pathway, and thus mediating the process of cognitive dysfunction in aged rats.