We studied correlation dependences between physiological parameters in rats in 3 h, 1 day, and 8 days after administration of LPS (100 μg/kg) at the end of 24-h immobilization stress. In 3 h after LPS administration against the background of stress exposure, significant correlations of metabolic parameters with the relative weight of the adrenal glands and the perceptual component of nociception in rats were revealed. A direct relationship between the concentration of the proinflammatory cytokine TNFα and anti-inflammatory IL-4 was also found in these animals. On the first day after LPS injection, correlations were revealed, predominantly positive, only between the indicators of the cytokine blood profile. In the late post-stress period after antigenic exposure, no correlations between the studied physiological parameters were found. It can be hypothesized that immune modulation through systemic administration of LPS prevents persistent excessive stress of physiological functions at the later stages after stress exposure.

https://link.springer.com/content/pdf/10.1007/s10517-021-05320-2.pdf

Correlation of Physiological Parameters in Rats after Stress Exposure under Conditions of Antigenic Stimulation with Lipopolysaccharide Administration.

Dynamics of Metabolic Measures in Rats at Different Stages of the Poststress Period in Conditions of Antigen Exposure by Administration of Lipopolysaccharide

Depression is a common mental illness, with an estimated 3.8% of global population affected. Peripheral administration of lipopolysaccharide (LPS) culminate in a distinct depressive-like behavioral syndrome, measured by increased duration of immobility in the forced swim test (FST) and anhedonia in sucrose preference tests (SPT). After 6 days of LPS stimulation, we established a depression model in C57BL/6 mice, where animals started to recover from the B/W loss brought on by the LPS and the significant immunological response that resulted in microglial activation in the brain. There was a modulation in the relative weight of the thymus and spleen observed under these experimental conditions. Ketamine having a quick onset of action reduces the emergence of depressive-like behaviour by modifying the intensity of Iba-1 in stressed mice by reducing swimming behaviour and boosting desire for sucrose. However, it did not result in an improvement in the number of microglia or CD11b cells activation in the hippocampus of C57BL/6 mice or in the relative weights of the spleen and thymus. In summary, these data emphasizes that Ketamine treatment improves depressive-like behavior and Iba-1 immunoreactivity, but the hyperactive in terms of number of microglia and CD11b expression were not modulated in the mouse hippocampus.

Evaluation of Ketamine after subacute low dosage Lipopolysaccharide-activated Microglia produced depressive-like phenotype in mice

Introduction: Thymus is the central lymphoid organ responsible for proper immune cell maturation, hence ensuring functional T cell repertoire. Stress induces elevated levels of hormones that profoundly alter immune response. Susceptibility to physiologically synthesised and exogenously applied glucocorticoids make thymus an ideal substrate for anatomical and morphological analysis. Aim: Our research aimed to investigate the impact of endogenous and exogenous glucocorticoids on thymus weight level. Material and methods: Experimental procedure was conducted on male Wistar rats, 12 in total, divided into 2 groups - control and experimental. Latter was exposed to two kinds of stressors. Acute stress included immobilization with exposure to the predator's odor. Chronic social stress included rotation of the animals held in pairs. On the 11th day of the experimental procedure, half of the experimental group received dexamethasone treatment (impact of endogenous + exogenous glucocorticoids) while the other half did not (impact of endogenous glucocorticoids). After the experiment, animals were sacrificed and their thymuses were obtained and measured. For statistical analysis, ANOVA was used to test differences between groups and LSD test for each group testing. Results: Results showed statistically significant differences between the thymus mass of different groups (F=4.336, p=0.048). The part of the experimental group that received dexamethasone had a smaller thymus weight level compared to the part of the experimental group that received no treatment (p=0.024). No statistically relevant results were obtained after comparing thymus masses from impact of endogenous glucocorticoids and control group (p>0.05). Conclusion: Exogenous glucocorticoids induce morphological changes in thymus which are observed in decreased weight level. Stress induced thymus apoptosis, but it was not sufficient to lead to decrease in thymic mass. Our further experiments will put emphasis on understanding of morphological and anatomical changes caused by stress.

The effect of traumatic exposure on thymus weight level after dexamethasone application in rats

Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder occurring in susceptible individuals following a traumatic event. Understanding the mechanisms subserving trauma susceptibility/resilience is essential to develop new effective treatments. Increasing evidence suggests that non-coding RNAs, such as microRNAs (miRNAs), may play a prominent role in mediating trauma susceptibility/resilience. In this study, we evaluated the transcriptional expression of two key PTSD-related genes (FKBP5 and BDNF) and the relative targeting miRNAs (miR-15a-5p, miR-497a-5p, miR-511-5p, let-7d-5p) in brain areas of PTSD-related susceptible and resilient mice identified through our recently developed mouse model of PTSD (arousal-based individual screening (AIS) model). We observed lower transcript levels of miR-15a-5p, miR-497a-5p, and miR-511a-5p in the hippocampus and hypothalamus of susceptible mice compared to resilient mice, suggesting that the expression of these miRNAs could discriminate the two different phenotypes of stress-exposed mice. These miRNA variations could contribute, individually or synergically, to the inversely correlated transcript levels of FKBP5 and BDNF. Conversely, in the medial prefrontal cortex, downregulation of miR-15a-5p, miR-511-5p, and let-7d-5p was observed both in susceptible and resilient mice, and not accompanied by changes in their mRNA targets. Furthermore, miRNA expression in the different brain areas correlated to stress-induced behavioral scores (arousal score, avoidance-like score, social memory score and PTSD-like score), suggesting a linear connection between miRNA-based epigenetic modulation and stress-induced phenotypes. Pathway analysis of a miRNA network showed a statistically significant enrichment of molecular processes related to PTSD and stress. In conclusion, our results indicate that PTSD susceptibility/resilience might be shaped by brain-area-dependent modulation of miRNAs targeting FKBP5, BDNF, and other stress-related genes.

Dysregulation of miR-15a-5p, miR-497a-5p and miR-511-5p Is Associated with Modulation of BDNF and FKBP5 in Brain Areas of PTSD-Related Susceptible and Resilient Mice.

We studied the effect of LPS on the state of stress-marker organs in rats at various periods after a single exposure to long-term stress on the model of 24-h immobilization. The animals were intraperitoneally injected with LPS in a dose of 100 μg/kg immediately after the negative emotiogenic exposure. Changes in physiological parameters were evaluated 3 h, 1 day, and 8 days after immune stimulation. Acute stress was accompanied by a decrease in the weight of the thymus during all stages of the post-stress period. An increase in the relative weight of theadrenal glands in animals under these conditions was observed only on day 8 after restraint stress. The induction of immune reactions due to systemic treatment with LPS was shown to prevent involution of the spleen in the late stage after a single exposure to long-term stress (day 8). Hypertrophy of the adrenal glands, which serves as one of the typical reactions of mammals to negative emotiogenic factors, was not revealed during the post-stress period after antigenic stimulation. These data hold much promise for the development of new approaches to the use of immunoactive substances to prevent or reduce the severity of physiological changes after emotiogenic loads.

State of Stress-Marker Organs in Rats after a Single Exposure to Long-Term Stress and Treatment with Lipopolysaccharide.

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State of Stress-Marker Organs in Rats after a Single Exposure to Long-Term Stress and Treatment with Lipopolysaccharide.