Introduction: Vitamin D is a fat-soluble secosteroid, its primary function being regulation of calcium-phosphate homeostasis and maintenance of bone integrity and mineralization. Recently, pleotropic effects of this vitamin have been recognized, including an immunomodulatory role and involvement in normal brain development and functioning. Aim: The aim of the present study was to investigate the influence of cholecalciferol on serum inflammatory markers and memory functions in lipopolysaccharide (LPS) model of inflammation. Materials and methods: Male Wistar rats were randomly divided into 4 groups (n=8): control group, LPS control group, LPS + cholecalciferol (vitamin D3) 500 UI group, and 1000 IU/kg bw group. Step-down passive avoidance test, novel object recognition test (NORT), Y- and T-maze were performed to assess the memory functions. Latency, recognition index (RI), % spontaneous alteration (SA), and working memory index were registered. Tumor necrosis factor-alpha (TNF-α), IL-1β, transforming growth factor-β1 (TGF-β1), and brain derived neurotrophic factor (BDNF) serum levels were measured by ELISA. Results: LPS administration caused significant impairment in memory functions in all memory tasks. Cholecalciferol treatment caused significant increase in % SA, RI, and working memory index. In the step-down passive avoidance test, cholecalciferol-treated groups showed statistically significant increase in latency in the long-term memory test. Vitamin D3-treated rats showed decreased TNF-α and IL-1β serum levels whereas the concentration of TGF-β1 and BDNF increased. Conclusions: Cholecalciferol improves spatial working and episodic memory, which can at least partially be explained with its effect on systemic inflammatory response that is closely related with the development of neuroinflammation.
Nigella sativa (NS) is a promising medicinal plant with diverse therapeutic properties. This study aimed to investigate the impact of NS oil (NSO) on memory functions in rats with LPS (lipopolysaccharide)-induced neuroinflammation, as well as its effect on serum levels of inflammatory cytokines, neuropeptide Y (NPY) and brain-derived neurotrophic factor (BDNF). Male rats were divided into four groups: control, LPS-control, LPS+NSO 3 and 5 mL/kg. Neuroinflammation was induced by a single intraperitoneal LPS injection (2 mg/kg). The novel object recognition test (NORT) and Y-maze were used for the evaluation of memory processes. Recognition index (RI) and % spontaneous alteration (%SA) were registered, respectively. Blood samples for TNF-α, IL-1β, IL-10, BDNF, and NPY serum levels were taken. Thymoquinone, the active compound of the oil, was detected by high-performance liquid chromatography. NSO administration resulted in an improvement in spatial and episodic memory, as evidenced by increased % SA and RI compared to LPS-control. Treatment with NSO led to a significant reduction in pro-inflammatory cytokines and NPY, along with an increase in IL-10 and BDNF levels, when compared to LPS-control. In conclusion, NSO enhances BDNF production and regulates pro- and anti-inflammatory cytokines release, which probably contributes to the observed cognitive improvement in animals with experimental neuroinflammation.
Weightlessness significantly impacts physiological systems. In the current study, we investigate the effects of 7 days exposure of rats to simulated microgravity (using a modified rat-modeled random positioning machine, working with four experimental animals simultaneously) on local carrageenan-induced inflammation and serum levels of liver enzymes, metabolites (glucose, urea, creatinine), and metabolic hormones (thyroid-stimulating hormone – TSH, aldosterone, cortisol). Male Wistar rats (n=12, m=200 ± 20 g) were evenly divided into RPM (experimental) and RPM-K (control) groups. The RPM rats showed a notable mass decrease compared to the controls. A significant increase in the carrageenan-induced inflammatory response was reached on the 24th hour in the RPM group compared to the RPM-K. Simulated microgravity resulted in lower serum glucose, creatinine, cortisol, and elevated urea levels. In conclusion, 7 days of exposure to random positioning machine-simulated microgravity promotes a pro-inflammatory state, potentially affecting insulin sensitivity, glucose utilization, and muscle catabolism.
Circular RNAs (circRNAs) are small, non-coding RNAs in which the 5′ and 3′ ends are linked covalently by back-splicing of exons from a single pre-mRNA. More and more scientific evidence is gathered for their wide distribution in the animal world, playing the role of regulators for biological processes, being cell- and tissue-specific. They can influence cellular physiology by various molecular mechanisms, finally modulating gene expression. CircRNAs are believed nowadays to be expressed in both receptive and cancerous endometrium. Due to their abundant expression in the endometrial tissue and their small size and stability, they have been considered potential diagnostic markers and treatment targets for endometrial-related diseases. The regulation of proliferation and differentiation is essential for the formation of receptive endometrium and for endometrial cancer emergence and progression. The receptive endometrium can be regarded as the most highly differentiated state of the endometrium. In contrast, the cancerous endometrium is characterized by a high level of proliferation and the lowest degree of differentiation. These endometria could be conditionally considered opposites. We are investigating the circRNA–miRNA–mRNA regulatory networks that can promote or suppress the proliferation and differentiation of endometrial cells by activating specific signaling pathways in both receptive and cancerous endometria. It could be worth knowing whether there are universal endometrial switches responsible for proliferation and differentiation processes that can alter the balance between them. We are interested in their clinical application as biomarkers and therapeutic targets for both endometrial receptivity issues and EC cases, particularly in diagnosis, progression assessment, and outcome prediction.
Circular RNAs (circRNAs) are small, non-coding RNAs in which the 5’ and 3’ ends are linked covalently by back-splicing of exons from a single pre-mRNA. More and more scientific evidence is gathered for their wide distribution in the animal world, playing the role of regulators for biological processes, being cell and tissue-specific. They can influence cellular physiology by various molecular mechanisms, finally modulating gene expression. CircRNAs are believed nowadays to be expressed in both receptive and cancerous endometrium. Due to their abundant expression in the endometrial tissue and their small size and stability, they have been considered potential diagnostic markers and treatment targets for endometrial-related diseases. The regulation of proliferation and differentiation is important for the formation of receptive endometrium and for endometrial cancer emergence and progression. It may be worth investigating whether there are universal circRNAs-miRNAs-mRNAs regulatory networks that can promote or suppress the proliferation and differentiation of endometrial cells by activating specific signaling pathways in both receptive and cancerous endometrium.
Introduction: Parkinson’s disease (PD) is а neurodegenerative disorder characterized mainly by its motor symptoms. The non-motor symptoms including pain are increasingly recognized in the last few decades. Existing evidence suggests that the dopaminergic neurotransmission has an essential role in pain control.Aim: The aim of the present study was to investigate the antinociceptive effect of dopaminergic drugs pramipexole and tolcapone against chemical and thermal stimuli in naive rats.Materials and methods: Male Wistar rats divided into 8 groups (n=8): saline; diclofenac 25 mg/kg body weight (bw) (positive control); pramipexole 0.5; 1 and 3 mg/kg bw; tolacapone 5; 15 and 30 mg/kg bw. Paw pressure and plantar tests were performed. Paw withdrawal pressure and latent time were measured. Statistical analysis was done by SPSS 19.Results: In the paw pressure test, pramipexole, in a dose of 1 and 3 mg/kg bw and tolcapone in a dose of 30 mg/kg bw, increased significantly the latency at 1, 2, and 3 hours compared to saline (p<0.05). In the plantar test, only the highest dose of pramipexole reached significance at 3 hours compared to the control rats (p<0.05). In contrast to pramipexole the three experimental groups with tolcapone markedly increased the latent time at 1 and 3 hours compared to saline (p<0.05).Conclusions: Pramipexole and tolcapone reduce mechanical and thermal nociception in naïve rats by enhancing dopaminergic neurotransmission at both spinal and supraspinal levels. In addition, tolcapone stimulates noradrenergic mediation which may contribute to its antinociceptive effect.