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Clinical studies have found that ketamine has a rapid and lasting antidepressant effect, especially in the case of patients with major depressive disorder (MDD). The molecular mechanisms, however, remain unclear. In this study, we observe the effects of S-Ketamine on the expression of Rac1, neuronal morphology, and synaptic transmission function in the hippocampus of stressed rats. Chronic unpredictable mild stress (CUMS) was used to construct stressed rats. The rats were given a different regimen of ketamine (20 mg/kg, i.p.) and Rac1 inhibitor NSC23766 (50 µg, ICV) treatment. The depression-like behavior of rats was evaluated by sucrose preference test and open-field test. The protein expression of Rac1, GluA1, synapsin1, and PSD95 in the hippocampus was detected by Western blot. Pull-down analysis was used to examine the activity of Rac1. Golgi staining and electrophysiological study were used to observe the neuronal morphology and long-term potentiation (LTP). Our results showed that ketamine can up-regulate the expression and activity of Rac1; increase the spine density and the expression of synaptic-related proteins such as GluA1, Synapsin1, and PSD95 in the hippocampus of stressed rats; reduce the CUMS-induced LTP impairments; and consequently improve depression-like behavior. However, Rac1 inhibitor NSC23766 could have effectively reversed ketamine-mediated changes in the hippocampus of rats and counteracted its antidepressant effects. The specific mechanism of S-Ketamine's antidepressant effect may be related to the up-regulation of the expression and activity of Rac1 in the hippocampus of stressed rats, thus enhancing synaptic plasticity.
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Trastorno Depresivo Mayor , Ketamina , Ratas , Animales , Ketamina/farmacología , Ketamina/metabolismo , Ketamina/uso terapéutico , Depresión/tratamiento farmacológico , Depresión/metabolismo , GTP Fosfohidrolasas/metabolismo , GTP Fosfohidrolasas/farmacología , GTP Fosfohidrolasas/uso terapéutico , Trastorno Depresivo Mayor/metabolismo , Estrés Psicológico/complicaciones , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Antidepresivos/metabolismo , Plasticidad Neuronal , Hipocampo/metabolismo , Modelos Animales de Enfermedad , Proteína de Unión al GTP rac1/metabolismoRESUMEN
The purpose of this study was to investigate the effects of propofol anesthesia combined with remifentanil on inflammation, stress response, and immune function in children undergoing tonsil and adenoid surgery. For this aim, 126 children admitted to our hospital for elective temperature-controlled radio-frequency of tonsils and adenoids from October 2020 to September 2021 were randomly divided into an observation group (n=63) and a control group (n=63). The observation group was anesthetized with propofol in combination with remifentanil, while the control group underwent propofol combined with ketamine. The mean arterial pressure (MAP), heart rate, serum C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), epinephrine, cortisol (Cor), CD3+ T lymphocytes, CD4+ helper T lymphocytes, CD8+ suppressor T lymphocytes and CD4+/CD8+ ratio were compared between the two groups before induction of anaesthesia (T1), upon intubation (T2), at the beginning of surgery (T3), at the end of surgery (T4) and 5 min after extubation (T5). -(TNF-α). The recovery time from anaesthesia and adverse reactions after extubation were observed in the two groups. Results showed that the MAP and heart rate in both groups increased significantly at T2 compared to T1, but the observation group had lower values than the control group after the maintenance of anaesthesia (P<0.05). Serum CRP, IL-6 and TNF-α levels increased with time in both groups, and the increase was considered significant (P<0.05). In addition, serum epinephrine and Cor levels gradually rose from T1 to T4 in both groups, and then decreased at T5. The difference was statistically significant (P<0.05) between any two-time points. CRP, IL-6, TNF-α, epinephrine and Cor in the observation group were significantly lower than those in the control group from T3 to T5 (P<0.05). CD3+, CD4+ and CD4+/CD8+ ratio decreased whereas CD8+ went up in both groups at T4 and T5, and which were considered statistically significant when compared with data from T1 to T3 (P<0.05). However, CD3+, CD4+, CD8+ and CD4+/CD8+ ratios did not differ statistically significantly between the two groups at each time point (P>0.05). In the observation group, the time to recovery of spontaneous respiration, the time to resumption of limb movements and the span from discontinuation of anaesthetic to extubation were all significantly shorter than those in the control group, and the incidence of agitation during the awakening period was lower than that in the control group (P<0.05). Then propofol combined with remifentanil is more effective in inflammation, stress response and immune function in anesthetizing children undergoing tonsil and adenoid surgery. The observation group presented more stable hemodynamics, lower levels of inflammation and stress reactions, rapid awakening and fewer adverse effects, so the combination therapy was worthy of clinical promotion in pediatric surgery requiring general anesthesia.
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Tonsila Faríngea , Propofol , Tonsila Faríngea/cirugía , Anestesia General , Proteína C-Reactiva , Niño , Epinefrina , Humanos , Inmunidad , Inflamación , Interleucina-6 , Tonsila Palatina/cirugía , Propofol/farmacología , Propofol/uso terapéutico , Remifentanilo , Factor de Necrosis Tumoral alfaRESUMEN
BACKGROUND: Relative fat mass (RFM) is a novel indicator for measuring body fat. The relationship between RFM and depression was explored using National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2018. METHODS: A general statistical description of the population included in the study was performed, and logistic analyses were used to explore the association between body mass index (BMI), waist circumference (WC), RFM and depression. Sensitivity analyses and restricted cubic spline (RCS) were also conducted to investigate the association between RFM and depression. RESULTS: A total of 28,836 participants were included in the study. In multivariate models, all obesity indices were associated with depression (P < 0.001). An increase of 1 SD in BMI, WC, and RFM was associated with a respective increased risk of depression of 2.3 %, 1.0 %, and 3.3 %. Excluding those taking antidepressants, the risk of depression was OR 1.88 (95 % CI: 1.26-2.79) for those with RFM in the highest quartile compared with those in the lowest quartile. After Inverse probability of weighting (IPW), the risk of depression in individuals with RFM in the highest quartile compared with individuals in the lowest quartile was 2.62 (95 % CI: 2.21-3.09). The RCS showed a possible nonlinear relationship between RFM and depression. CONCLUSIONS: RFM is associated with depression, suggesting that attention to RFM may be helpful for depression research.
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Índice de Masa Corporal , Depresión , Encuestas Nutricionales , Obesidad , Circunferencia de la Cintura , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Depresión/epidemiología , Obesidad/epidemiología , Tejido Adiposo , Estudios Transversales , Factores de Riesgo , Anciano , Adulto JovenRESUMEN
Background: Lipid Accumulation Product (LAP) is a new type of obesity index. The relationship between LAP and depression is unclear, and this cross-sectional study was conducted to explore the relationship between LAP and depression using the National Health and Nutrition Examination Survey (NHANES) database from 2005-2018. Methods: In our study, logistic regression analysis was used to calculate the odds ratio between depression and LAP, and subgroup analysis and sensitivity analysis were also performed to verify the robustness of the results. Results: The analysis included 13,240 participants aged 20 years or older. After adjusting for multiple variables, LAP was positively associated with depression, OR 1. 50 (95% CI, 1. 05-2. 12). In subgroup analysis, LAP was significantly positively, associated with depression among male (2. 52, OR; 95% CI, 1. 39,4. 57), non-Hispanic Black (2. 55, OR; 95% CI, 1. 49,4. 36), those without diabetes (1. 67, OR; 95% CI, (1. 06,2. 61) or in the overweight (2. 09, OR; 95% CI, (1. 23,3. 54) subgroups. After inverse probability of treatment weighting (IPTW), the OR for the highest versus lowest quartile was 1. 55 (95% CI: 1. 24 - 1. 95). Conclusion: There are positive results between LAP and depression after adjusting for multiple potential variables, and prospective studies are needed to verify the results.
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Objectives: Non-high-density lipoprotein cholesterol (non-HDL-C) has attracted attention because it is associated with a variety of diseases and is easy to measure. However, the relationship between non-HDL-C and depression is still unclear. Our aim was to assess the relationship between non-HDL-C and depression using the cross-sectional NHANES survey from 2005 to 2018. Methods: We examined the association between non-HDL-C and depression using weighted multivariable logistic regression models and subgroup analysis. Sensitivity analysis demonstrated the robustness of the results. Results: There were 42,143 participants in this study and 8.6% had depression (weighted 7.53%). Non-HDL-C was higher in participants with depression compared to those without depression (weighted mean 3.64 vs. 3.73, p < 0.01). There was a positive association between non-HDL-C and depression with a 95% OR of 1.22 adjusted for multifactorial (95% CI,1.03-1.45). In subgroup analyses, non-HDL-C was positively associated with depression in men (OR, 1.31; 95% CI, 1.01-1.70), normal BMI (OR: 0.93; 95% CI: 0.66-1.32) and in participants without hypertension (OR, 1.29; 95% CI, 1.01-1.66). Conclusion: Non-HDL-C positively correlated with depression, and further research may be better for clinical service.
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Background: Postoperative delirium (POD) commonly occurs in patients following major surgeries and is associated with adverse prognosis. The modes of anesthesia may be associated with POD occurrence. General anesthesia (GA) causes loss of consciousness in the patient by altering the levels of some neurotransmitters as well as signaling pathways. We conducted this meta-analysis to investigate the effect of GA vs. regional anesthesia (RA) on POD incidence in surgical patients. Methods: The databases of Pubmed, Embase, and Cochrane Library were searched till October 22, 2021. The eligible criteria were participants aged 18 years or older, patients undergoing surgery under GA and RA, and articles reporting the effect of GA vs. RA on POD incidence. RevMan 5.3 was used to perform statistical analyses. Results: A total of 21 relevant trials with a total of 1,702,151 patients were included. The pooled result using random-effects model with OR demonstrated significant difference in POD incidence between patients with GA and RA (OR = 1.15, 95% CI: [1.02, 1.31], I 2 = 83%, p for effect = 0.02). We did not obtain the consistent pooled result after sensitivity analysis (OR = 0.95, 95% CI: [0.83, 1.08], I 2 =13%, p for effect = 0.44) and excluded the articles without the information on preoperative cognitive or neuropsychological assessment (OR = 1.12, 95% CI: [1.00, 1.25], I 2 =80%, p for effect = 0.05), respectively. Conclusion: This meta-analysis could not identify that GA was significantly associated with POD occurrence in surgical patients compared with RA.
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Background: Postoperative delirium (POD) is common in patients following cardiac surgery. According to studies on non-cardiac surgery, males suffered from higher incidence of POD. However, there is no report about effect of gender differences on POD occurrence in cardiac surgery patients. The aim of this study was to investigate the effect of gender differences on POD occurrence in adult patients after cardiac valve surgery. Methods: This is a retrospective case-control study. We recorded the clinical data in adult patients who underwent elective cardiac valve surgery from May 2019 to October 2020. POD was assessed by the Confusion Assessment Method for Intensive Care Unit. Univariate analysis was used to screen the potential risk factors. Collinearity analysis was conducted to detect overlapping predictor variables on the outcomes. A multivariate logistic regression with odds ratio (OR) and 95% confidence interval (CI) was used to identify the independent risk factors. The Hosmer-Lemeshow test was performed to show the good calibration of the logistic regression model. Results: In total, we recorded the perioperative data in 431 adult patients, including 212 males and 219 females. Sixty patients suffered from POD, including 39 males and 21 females. Twenty-one perioperative variables were selected, and 11 were screened by univariate analysis. We did not detect the severe collinearity among the 11 variables. Male gender was identified as a significant risk factor in POD occurrence in patients undergoing cardiac surgery (Adjusted OR: 2.213, 95% CI: 1.049-4.670, P = 0.037). The Hosmer-Lemeshow test demonstrated good calibration of the logistic regression model (χ2 = 7.238, P = 0.511). Besides, compared with females, the relationship of male and delirium subtypes was as follows: (1) hyperactive: adjusted OR: 3.384, 95% CI: 1.335-8.580, P = 0.010; (2) hypoactive: adjusted OR: 0.509, 95% CI: 0.147-1.766, P = 0.287. A Stratification analysis by age demonstrated that the males showed higher POD incidence in patients aged younger than 60 years (adjusted OR: 4.384, 95% CI: 1.318-14.586, P = 0.016). Conclusions: Male gender is an important risk factor in POD occurrence in patients following cardiac surgery. Furthermore, the incidence of hyperactive delirium is higher in males. Besides, the male patients aged younger than 60 years are at high risk of POD. We should pay more attention to the male patients to prevent their POD occurrence.
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Background: The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of remimazolam in clinical endoscopic procedure sedation. Methods: The authors searched the databases of PubMed, Embase, and Cochrane Library for studies published until January 2, 2021, that reported remimazolam sedation for endoscopic procedures. The sedative efficiency and the incidence of adverse events were assessed as outcomes. Cochrane Review Manager Software 5.3 was used to perform the statistical analyses. Results: Seven relevant studies involving a total of 1,996 patients were identified. We conducted a meta-analysis of the different controls used in the studies, that is, the placebo, midazolam, and propofol. The results demonstrated that remimazolam had a strong sedative effect, and its sedative efficiency was significantly higher than that of placebo [OR = 0.01, 95% CI: (0.00, 0.10), I 2 = 30%, p <0.00001]. The sedative efficiency of remimazolam was significantly higher than that of midazolam [OR = 0.12, 95% CI: (0.08, 0.21), I 2 = 0%, p < 0.00001] but lesser than that of propofol [OR = 12.22, 95% CI: (1.58, 94.47), I 2 = 0%, p = 0.02]. Regarding the adverse events, remimazolam is associated with a lower incidence of hypotension than placebo and midazolam. Similarly, remimazolam was associated with a lower incidence of hypotension and hypoxemia than propofol. Conclusions: Remimazolam is a safe and effective sedative for patients undergoing endoscopic procedures. The sedative efficiency of remimazolam was significantly higher than that of midazolam but slightly lower than that of propofol. However, the respiration and circulation inhibitory effects of remimazolam were weaker than those of midazolam and propofol.
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Electroconvulsive therapy (ECT) is an efficient therapy for major depression and modern ECT requires anesthesia to enhance safety. However, the commonly used anesthetic, propofol, may weaken the treatment efficacy. A recent study confirmed that ketamine rapidly reduced the symptoms of depression in affected patients. A previous study found that electroconvulsive seizure (ECS), the animal model for ECT, under anesthesia of low-dose ketamine combined with propofol could enhance the antidepressant efficacy and improve the cognitive performance. The present study aimed to investigate the responses to different charges (0, 60, 120, 180 or 240 mC) of ECS under compound anesthetics, ketamine combined with propofol, in stressed rats and the underlying mechanisms to aid in optimization of treatment regimens. The results indicated that ECS exhibited an improved antidepressant effects at 120 mC compared with 60 mC, however, no significant differences in antidepressant effects were identified among the 120, 180 and 240 mC groups. Furthermore, rats subjected to ECS at 120 mC exhibited the best cognitive performance. The phosphorylation levels of calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) at Thr286, glutamate receptor 1 (GluR1) at Ser831 and cAMP-response element-binding protein (CREB) at the Ser133 were higher in the 120-mC group compared with all other groups. These results indicated that the ECS at medium intensity (120 mC) with administration of compound anesthetics may exert an improved therapeutic effect on depression compared with other intensities (0, 60, 180 and 240 mC). The results also suggested that the improvement in cognitive function in stressed rats may be attributed to the phosphorylation of CaMKIIα (Thr286), GluR1 (Ser831) and CREB (Ser133).
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Some studies have indicated that ketamine has a rapid antidepressant effects, but the underlying molecular mechanism is still unclear. Researchers have found that mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF are related to depression; they elicit opposite effects on cellular functions. It is clear that tissue plasminogen activator (tPA) is a key regulatory element in the conversion of proBDNF to mBDNF. The chronic unpredicted mild stress (CUMS) procedure is a classical and reliable method to establish the model of depression. This study found that sucrose preference and locomotor activity were both reduced in CUMS-treated rats while were increased in those who were injected with ketamine. The hippocampal proBDNF/mBDNF ratio was downregulated after ketamine treatment in those rats, together with an increased level of tPA in the hippocampus. However, tPA activity was unaltered after ketamine intraperitoneal injection. Intrahippocampal injection of active plasminogen activator inhibitor-1 (inhibitor of tPA) before ketamine treatment reversed the antidepressant effects and upregulated the proBDNF/mBDNF ratio. The results of this study suggest that the antidepressant action induced by ketamine may be related to tPA-mediated conversion of proBDNF to mBDNF in the hippocampus.
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Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/metabolismo , Hipocampo/metabolismo , Ketamina/administración & dosificación , Precursores de Proteínas/metabolismo , Activador de Tejido Plasminógeno/metabolismo , Anestésicos Disociativos/administración & dosificación , Animales , Antidepresivos/administración & dosificación , Depresión/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Inyecciones Intraventriculares , Masculino , Proteínas de Plantas/administración & dosificación , Ratas , Ratas Sprague-Dawley , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo , Activador de Tejido Plasminógeno/antagonistas & inhibidoresRESUMEN
Clinical studies on the role of the glutamatergic system in the pathogenesis of depression found that ketamine induces an antidepressant response, but the molecular mechanisms remain unclear. The present study investigated the effects of sub-anesthetic doses of ketamine on the glutamate reuptake function in the rat hippocampus. Chronic unpredictable mild stress (CUMS) was applied to construct animal models of depression. Sixty adult male Sprague-Dawley rats were randomly assigned to 5 groups and received a different regimen of CUMS and ketamine (10, 25, and 50mg/kg) treatment. The sucrose preference test and open-field test were used to assess behavioral changes. The expression levels of excitatory amino acid transporters (EAATs) were measured by western blot. Microdialysis and high-performance liquid chromatography (HPLC) were used to detect hippocampal glutamate concentrations. We found that the expression of EAAT2 and EAAT3 were obviously downregulated, and extracellular concentrations of glutamate were significantly increased in the hippocampi of depressive-like rats. Ketamine (10, 25, and 50mg/kg) upregulated the expression of EAAT2 and EAAT3, decreased the hippocampal concentration of extracellular glutamate, and alleviated the rats' depressive-like behavior. The antidepressant effect of ketamine may be linked to the regulation of EAAT expression and the enhancement of glutamate uptake in the hippocampus of depressive-like rats.
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Sistema de Transporte de Aminoácidos X-AG/metabolismo , Anestésicos/farmacología , Conducta Animal/efectos de los fármacos , Hipocampo/efectos de los fármacos , Ketamina/farmacología , Animales , Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Hipocampo/metabolismo , Masculino , Ratas Sprague-Dawley , Estrés Psicológico/tratamiento farmacológico , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Electroconvulsive therapy (ECT) is an effective treatment for depression, but it can induce learning and memory impairment. Our previous study found propofol (γ-aminobutyric acid (GABA) receptor agonist) could ameliorate electroconvulsive shock (ECS, an analog of ECT to animals)-induced cognitive impairment, however, the underlying molecular mechanisms remain unclear. This study aimed to investigate the effects of propofol on metaplasticity and autophosphorylation of CaMKIIa in stressed rats receiving ECS. Depressive-like behavior and learning and memory function were assessed by sucrose preference test and Morris water test respectively. LTP were tested by electrophysiological experiment, the expression of CaMKIIa, p-T305-CaMKII in hippocampus and CaMKIIα in hippocampal PSD fraction were evaluated by western blot. Results suggested ECS raised the baseline fEPSP and impaired the subsequent LTP, increased the expression of p-T305-CaMKII and decreased the expression of CaMKIIα in hippocampal PSD fraction, leading to cognitive dysfunction in stressed rats. Propofol could down-regulate the baseline fEPSP and reversed the impairment of LTP partly, decreased the expression of p-T305-CaMKII and increased the expression of CaMKIIα in hippocampal PSD fraction and alleviated ECS-induced learning and memory impairment. In conclusion, propofol ameliorates ECS-induced learning and memory impairment, possibly by regulation of synaptic metaplasticity via p-T305-CaMKII.
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Proteínas Portadoras/metabolismo , Depresión/psicología , Hipocampo/fisiología , Aprendizaje/efectos de los fármacos , Memoria/efectos de los fármacos , Propofol/farmacología , Animales , Proteínas de Unión al Calcio , Trastorno Depresivo/terapia , Terapia Electroconvulsiva/métodos , Electrochoque/métodos , Agonistas de Receptores de GABA-A , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Trastornos de la Memoria/tratamiento farmacológico , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The muscle mass decreases with age, leading to frailty and weakness; however, the role of acetylcholine receptors in this process has not been properly studied. In this article, we hypothesize that diaphragmatic as well as peripheral muscle weakness may be caused by the up-regulation of gamma and alpha 7 nicotinic acetylcholine receptors (nAChRs) on muscle cell membranes. METHOD: Adult male rats were randomly divided into sham and sepsis groups. Sepsis was induced by cecal ligation and puncture (CLP). Blood specimens and biopsies of tibialis anterior muscle and diaphragm were obtained at 24h post CLP. RESULTS: Up-regulation of gamma and alpha 7 nAChRs was detected in both sham and septic groups; however, this response was more robust in septic animals. Compared to tibialis anterior muscle, the diaphragm expressed a higher number of both receptor types. CONCLUSIONS: Muscle weakness in old age and sepsis may have common molecular underpinnings. Loss of diaphragmatic strength may explain hypoxia and respiratory failure often encountered in frail elderly.
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Envejecimiento/fisiología , Músculo Esquelético/metabolismo , Receptores Nicotínicos/metabolismo , Sepsis/metabolismo , Regulación hacia Arriba , Animales , Diafragma/metabolismo , Interleucina-6/sangre , Masculino , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Electroconvulsive therapy (ECT) is an effective treatment for depression, but can result in memory deficits. This study aimed to determine whether ketamine could alleviate electroconvulsive shock (ECS, an analog of ECT in animals)-induced memory impairment and the potential molecular mechanism. Chronic unpredictable mild stress was used to generate animal models of depressive-like symptoms. Sixty adult male Sprague-Dawley rats were randomly divided into the following five groups: control group (group C); depressive-like model group (group D); ECS group (group DE); ketamine+ECS group (group DKE); and ketamine group (group DK). The sucrose preference test and Morris water maze were used to assess behavioral changes. The expression levels of Iba-1, IL-1ß and TNF-α were measured by immunohistochemistry and real-time PCR. Enzyme-linked immunosorbent assays were used to detect the levels of soluble Aß. We found that ECS up-regulated the expression of Iba-1, promoted the release of IL-1ß and TNF-α, increased the levels of Aß1-40 and Aß1-42 in the hippocampus, and aggravated memory impairment of the depressive-like rats. However, ketamine reversed these ECS-induced molecular changes and effectively attenuated ECS-induced memory impairment. This cognitive protective effect of ketamine may be attributed to its suppression of ECS-induced neuroinflammation and reduction of the levels of soluble Aß.
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Péptidos beta-Amiloides/metabolismo , Antiinflamatorios/uso terapéutico , Depresión/terapia , Electrochoque/efectos adversos , Ketamina/uso terapéutico , Trastornos de la Memoria/tratamiento farmacológico , Fragmentos de Péptidos/metabolismo , Animales , Proteínas de Unión al Calcio/metabolismo , Depresión/metabolismo , Depresión/psicología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/etiología , Inflamación/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/etiología , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/psicología , Proteínas de Microfilamentos/metabolismo , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Solubilidad , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Electroconvulsive therapy (ECT) is an effective treatment for major depression, but can result in memory impairment. Several studies have shown that anesthetic propofol can alleviate the impairment of memory induced by ECT. However, the underlying molecular mechanisms remain unclear. We aimed to investigate the effects of propofol and electroconvulsive shock (ECS, analog of ECT in animals) on hippocampal inflammatory cytokines and glutamate uptake in depressed rats. The chronic unpredictable mild stress (CUMS) procedure was adopted to establish a model of depression. Sixty adult Sprague-Dawley rats were randomly divided into 5 groups with the following assignments (n=12 for each group): group C: control group without treatment; group D: CUMS+sham ECS; group DE: CUMS+ECS; group DP: CUMS+propofol (80 mg/kg, i.p.); group DPE: CUMS+propofol (80 mg/kg, i.p.)+ECS. Sucrose preference test and Morris water maze were used to assess behavioral changes. Hippocampal glutamate levels were measured with high performance liquid chromatography and the expression levels of IL-1ß, TNF-α, GLAST and GLT-1 was quantificational analyzed by real time PCR or Western Blotting. The results demonstrated that ECS increased the levels of IL-1ß and TNF-α, down-regulated the expression of GLT-1, GLAST expression remains stable, heightened the concentration of glutamate in the hippocampus and aggravated learning and memory impairment of depressed rats. Propofol suppressed IL-1ß and TNF-α production, up-regulated the expression of GLT-1, decreased the concentration of glutamate in the hippocampus and attenuated the impairment of learning and memory induced by ECS. Propofol alleviate the learning and memory impairment induced by ECS could be partly attributed to its anti-inflammatory effects. This article is part of a Special Issue entitled Brain and Memory.