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Abstract* Introduction: Chronic morphine exposure can cause addiction and affect synaptic plasticity, but the underlying neural mechanisms of this phenomenon remain unknown. Herein we used electrophysiologic approaches in hippocampal CA1 area to examine the effect of chronic morphine administration on short-term plasticity. Methods: Experiments were carried out on hippocampal slices taken from either control animals or animals made dependent via oral chronic morphine administration. Population spikes (PSs) were recorded from stratum pyramidale of CA1 following stimulation the Schaffer collateral afferents. For examining the short-term synaptic plasticity, paired pulse stimulations with inter pulse interval (IPI) of 10, 20, 80, and 200 ms were applied and paired pulse index (PPI) was calculated. Results: Chronic morphine exposure had no effect on the baseline response. A significant increase in PPI was observed in dependent slices at 80 ms IPI as compared to the control ones. There was no significant difference in baseline response between control and dependent slices when we used long term morphine, naloxone, and both. However, long term morphine administration caused significant difference in PPI at IPI of 20 ms. This effect was eliminated in the presence of naloxone. Conclusion: These findings suggest that morphine dependence could affect short-term plasticity in hippocampal CA1 area and increase the hippocampus network excitability. Keywords: Addiction, CA1 neural networks, short-term synaptic plasticity.

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Introduction: Based on human studies, inequality and social injustice have adverse effects on the individual and community health. In this study, the effects of food intake inequality and social status changes on pain perception and immunological factors were investigated in Balb/C mice. Methods: The present study was conducted by implementing different social stresses including food deprivation, food intake inequality and unstable social status (cage-mate change every 3 days) in 48 female mice. Formalin test was performed and thereafter the viability of peritoneal macrophages and spleen lymphocytes was evaluated by MTT assay. Concentrations of proinflammatory cytokines including IL-6, IL- 1 and TNF-α were also measured. Results: Our results showed that the implementation of food deprivation and inequality induced significant changes in chronic phase of formalin test compared to the control group (P<0.05). Pain perception was considerably decreased and this decline in inequality exposed subjects was well above the isolated ones. However, unstable social situation did not affect pain perception. Moreover, cell viability of peritoneal macrophages decreased, while cell viability of spleen lymphocytes and proinflammatory cytokines concentrations were increased in the serum of all stressed animals in comparison with controls (P<0.05). Conclusion: These results revealed that although food deprivation and social inequality can induce analgesia, some socioeconomic situations like social instability does not affect pain perception. All of these situations decrease cell viability in macrophages but enhance cell viability in lymphocytes. It seems that a proinflammatory stress condition is involved in these situations.

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Introduction: Several reports show a relationship between health equity, and health status and longevity of individuals. In this study, effects of food deprivation, inequality and social instability were investigated on the formation of lipofuscin pigment in Balb/C mice by histopathological and biochemical methods. Methods: Thirty-six male mice were divided into 6 groups, then different kinds of stress (food deprivation, inequality and cage-mate change) were implemented on these groups for 2 weeks according to the protocol. Lipofuscin was biochemically measured in the brain homogenate of one hemisphere by Shen’s method. The other brain hemisphere was used to qualitatively investigate the accumulation of lipofuscin by fluorescent microscope and it was also stained with periodic acid Schiff and examined with light microscope. Results: Food deprivation alone did not cause significant differences in the amount of lipofuscin, but in food deprived and inequality experienced animals the amounts of lipofuscin was well above controls (P<0.05) moreover, in the mice, which merely experienced unstable social status, the increase of lipofuscin was significant compared to the controls (P<0.001). When all of three social stresses were applied simultaneously, lipofuscin changes were more obvious. The microscopic examination of tissue samples showed accumulation of lipofuscin in test conditions. Conclusion: Food deprivation, injustice and unstable social status, especially when are applied simultaneously, can increase brain lipofuscin levels. Considering the role of this pigment in aging, the probability of appearance of early aging can be considered after exposure to social stress.

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Introduction: The current investigations on Health Equity, primarily point to the harmful health consequences of being in a stressful social hierarchy. The repetitive nature of social conflicts seems to favor the induction of hyperalgesia or hypoalgesia both in rodents and humans, and it can also affect the immune system. In this study, the effects of changes in social status on pain perception as well as alterations of pro-inflammatory cytokines were investigated in Balb/C mice. Methods: By implementation of a sensory contact model in 22 male inbred mice (stress group) from 30 mice of the Balb/c strain and modeling of dominance/submissive relationship, each mouse was injected by 20 μl of formalin 2% and their pain behavior was scored, then serum concentrations of proinflammatory cytokines were measured in all mice. Results: Our results showed that subordinate mice in chronic phase of formalin test were hypoalgesic as compared to the control and dominant mice (P<0.05). On the other hand, dominant mice were hypoalgesic as regards to subordinate mice during acute phase of formalin test. IL-1 and IL-6 concentrations in serum of dominant and subordinate mice were well above the control group. Conclusion: These results revealed that despite similar increase of proinflammatory cytokines' level in dominant and subordinate subjects social status can differently affect pain perception.

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Introduction: Glioblastoma (GBM) is the most common malignant brain tumor, and the prognosis of GBM pa-tients is unfavorable. More studies are needed to develop new prognostic tools for predicting GBM patients’ prognosis. This study aims to construct generisk score (GRS) models based on gene expression databases.

Methods: Genomic data of GBM were downloaded from the CGGA, TCGA, MYO, and CPTAC. Patients were divided into two groups with overall survival (OS) of more or less than 15 months. Top 31 genes from our previous study and clinical data such as age, gender, and IDH wildtype/mutant were used to develop two GRS models. Cox methods in SPSS v26 were applied in this study.

Results: A total of 551 (334 male, mean age 55.5 ± 13.3 years) cases were used. Fourgene (TGFB1, CCL2, CD274, and TNFRSF1A; from the combination of four databases) and eight-gene (EGFR, TGFB1, SPP1, AGT, TNFRSF1A, CDK1, FOXO3, and CEP55; from CGGA) risk scores were developed. Two models could separate OS samples into high and low-risk groups, and AUCs of 0.984 and, 0.998 were achieved that showed excellent discriminating power at the training set (all: p < 0.0001). For the 8-GRS model, the OS of cases in the high-risk group was poorer than that in the low-risk group when used on another’s datasets at the validation set, however, it was not significant.

Conclusion: Four- and eight-gene prognostic signatures were identified and constructed to predict OS in GBM patients. This study may provide innovative insights into the treatment of GBM.

Supplementary File