Effects of Maternal Separation and Subsequent Stress on Behaviors and Brain Monoamines in Rats.

Childhood adversity can induce maladaptive behaviors and increase risk for affective disorders, post-traumatic stress disorder, personality disorders, and vulnerability to stress in adulthood. Deprivation of maternal care interrupts brain development through the disturbance of various neurotransmitters, however, the details remain unclear. The features of the symptoms of disorders are largely determined by early stress protocol, genetic characteristics (line), and the sex of the animals. The purpose of current study was (1) to assess behavioral changes in adult Wistar rats of both sexes after early life stress; (2) to determine the levels of monoamines in brain structures involved in the motor, emotional, and social reactions in rats aged 1 and 2 months; and (3) to determine the level of monoamines after physical or emotional stress in adult rats. The rat pups were separated from their dams and isolated from siblings in tight boxes at a temperature of 22-23 °C for 6 h during postnatal days 2-18. The data were processed predominantly using two-way analysis of variance and the Newman-Keys test as the post hoc analysis. The adult rats demonstrated an increase in motor activity and aggressiveness and a decrease in levels of anxiety and sociability. Behavioral disturbances were accompanied by region-, sex-, and age-dependent changes in the levels of monoamines and their metabolites. The dopaminergic and noradrenergic systems were found to be sensitive to psycho-emotional stress.

New Properties of a Well-Known Antioxidant: Pleiotropic Effects of Human Lactoferrin in Mice Exposed to Gamma Irradiation in a Sublethal Dose.

We studied the effects of human lactoferrin (hLf), a multifunctional protein from the transferrin family, on integral (survival, lifespan during the experiment, body weight, behavior, subfractional compositions of blood serum) and systemic (hemoglobin level, leukocyte number, differential leukocyte count, histological structure of the liver and spleen) parameters of the body in mice after acute gamma irradiation in a sublethal dose. The experiments were performed on male C57BL/6 mice. The mice in the experimental groups were exposed to whole-body gamma radiation in a dose of 7.5 Gy from a 60Co source. Immediately after irradiation and 24 h after it, some animals received an intraperitoneal injection of hLf (4 mg/mouse). Single or repeated administration of hLf had a positive pleiotropic effect on irradiated animals: animal survival increased from 28% to 78%, and the mean life expectancy during the experiment (30 days) increased from 16 to 26 days. A compensatory effect of hLf on radiation-induced body weight loss, changes in homeostasis parameters, and a protective effect on the structural organization of the spleen were demonstrated. These data indicate that Lf has potential as a means of early therapy after radiation exposure.

Low molecular weight NGF mimetic GK-2 normalizes the parameters of glucose and lipid metabolism and exhibits a hepatoprotective effect on a prediabetes model in obese Wistar rats.

Signs of metabolic syndrome and prediabetes preceding type 2 diabetes are modelled in an experiment using a high-fat diet (HFD). The aim of this work was to study the effect of a low molecular weight systemically active nerve growth factor mimetic, compound GK-2 (hexamethylenediamide bis[N-monosuccinyl-L-glutamyl-L-lysine]), on indicators of abdominal obesity, basal blood glucose level, glucose tolerance, cholesterol and triglyceride blood levels, as well as the morphological structure of the liver in male Wistar rats fed a HFD. Rats were divided into three groups: one of them received standard food (control) and two others were fed a HFD containing 45% fat, 35% carbohydrates and 20% protein, with a total caloric value of 516 kcal/100 g, over 12 weeks. Starting from the ninth week, for the next 4 weeks, one of the HFD groups was treated orally with saline whilst the other group was treated orally with GK-2 at a dose of 5 mg/kg. GK-2 was found to reduce the basal glycaemia level and improve glucose tolerance, as well as to reduce the blood level of cholesterol by 30% and that of triglycerides by 28% in comparison with the saline-treated HFD animals. GK-2 reduced the degree of abdominal obesity to the level of the healthy animals and eliminated morphological abnormalities in the liver caused by the HFD. The results of the study determine the feasibility of further GK-2 research as a potential agent for prediabetes treatment.

Cardiovascular system parameters in participants of Arctic expeditions.

OBJECTIVES: A method of continuous heart rate (HR) and blood pressure (BP) recording was used for the evaluation of the cardiovascular system parameters in participants of short-term (<1 month) high-latitude expeditions, in comparison with the parameters of residents of Central Russia and the Arctic region. MATERIAL AND METHODS: A dynamic examination of participants of Arctic expeditions (30 men, residents of middle-latitude regions, aged 46.7±1.7 years), workers permanently living in Central Russia (the Moscow region, 44 men, aged 46.7±1.0 years) and residents of the North (the Murmansk region, 35 men, aged 46.6±1.3 years) was performed. The authors used a spiroartheriocardiorythmograph allowing the parallel recording of HR, BP, spectral characteristics of HR variability (HRV) and the variability of systolic BP (sBP) and diastolic BP (dBP), cardiac performance parameters, and spontaneous baroreflex sensitivity (BRS). The parameters were recorded at rest, in a sitting position, over 2 min. RESULTS: The basic clinical parameters (HR, BP and cardiac performance) did not differ in the workers living in different climatic zones. However, the residents of the North demonstrated a lower total power (TP) of the dBP variability spectrum and a lower relative power of the high-frequency (HF) range in both the sBP and dBP variability spectra. The participants of expeditions to the North had a lower TP of the HRV spectrum (in comparison with both control groups) that did not change during the expeditions; BRS was reduced, while the TP of the sBP spectrum was increased in comparison with the corresponding parameters obtained from the residents of circumpolar regions, and decreased during the expedition in parallel with a decrease in the sBP values. The TP of both the sBP and dBP variability spectra, as well as the power of the HF range in these spectra, were similar in the participants of expeditions to those obtained from the residents of Central Russia, and they considerably surpassed the corresponding parameters in the northerners surveyed. CONCLUSIONS: The revealed peculiarities of the cardiovascular system in the participants of high-latitude expeditions can be considered as correlates of positive, and adequate in terms of the physiological value, adaptive shifts in the autonomous regulation of the cardiovascular system. Int J Occup Med Environ Health. 2020;33(6):819-28.

Streptozotocin (STZ)-Induced Diabetes Affects Tissue Trace Element Content in Rats in a Dose-Dependent Manner.

The objective of the present study was investigation of tissue trace element distribution in a streptozotocin model of DM1 in rats. DM1 was modeled in 2-month-old male Wistar rats (n = 30) using intraperitoneal injection of 45 mg/kg b.w. (STZ1) and 55 mg/kg b.w. streptozotocin (STZ2), whereas control animals were injected with physiological saline. The rats were subjected to oral glucose tolerance test (OGTT) and HbA1c level assessment at day 14. At day 30, blood serum, liver, kidney, and heart samples were collected for tissue trace element assessment using inductively coupled plasma mass spectrometry (ICP-MS). STZ-treated rats were characterized by lack of significant weight gain and elevated HbA1c and blood glucose levels. ICP-MS analysis demonstrated a dose-dependent accumulation of Cu, Mn, Mo, and Se levels in the liver. Correspondingly, the dose-dependent increase in renal Cu, Mn, V, and Zn levels was significant, whereas the observed trend for kidney V and Mo accumulation was nearly significant. The patterns of trace element content in the myocardium of STZ-exposed rats were quite different from those observed for liver and kidney. Only cardiac Zn content was characterized by a significant decrease. Serum Co, Cr, Cu, Se, V, and Mo levels were characterized by a significant decrease in response to STZ-induced diabetes. Generally, the obtained data demonstrate that diabetes is associated with altered copper, manganese, molybdenum, chromium, and vanadium handling. In turn, only altered Zn status may provide a link to diabetic cardiotoxicity. However, the particular mechanisms of both impaired metal handling in STZ diabetes and their potential anti-diabetic activity require further investigation.

Differential procoagulant activity of microparticles derived from monocytes, granulocytes, platelets and endothelial cells: impact of active tissue factor.

: Microparticles released by activated/apoptotic cells exhibit coagulation activity as they express phosphatidylserine and some of them - tissue factor. We compared procoagulant properties of microparticles from monocytes, granulocytes, platelets and endothelial cells and assessed the impact of tissue factor in observed differences. Microparticles were sedimented (20 000g, 30 min) from the supernatants of activated monocytes, monocytic THP-1 cells, granulocytes, platelets and endothelial cells. Coagulation activity of microparticles was examined using plasma recalcification assay. The size of microparticles was evaluated by dynamic light scattering. Tissue factor activity was measured by its ability to activate factor X. All microparticles significantly accelerated plasma coagulation with the shortest lag times for microparticles derived from monocytes, intermediate - for microparticles from THP-1 cells and endothelial cells, and the longest - for microparticles from granulocytes and platelets. Average diameters of microparticles ranged within 400-600 nm. The largest microparticles were produced by endothelial cells and granulocytes, smaller - by monocytes, and the smallest - by THP-1 cells and platelets. The highest tissue factor activity was detected in microparticles from monocytes, lower activity - in microparticles from endothelial cells and THP-1 cells, and no activity - in microparticles from platelets and granulocytes. Anti-tissue factor antibodies extended coagulation lag times for microparticles from monocytes, endothelial cells and THP-1 cells and equalized them with those for microparticles from platelets and granulocytes. Higher coagulation activity of microparticles from monocytes, THP-1 cells and endothelial cells in comparison with microparticles from platelets and granulocytes is determined mainly by the presence of active tissue factor.

Decreased adipose tissue zinc content is associated with metabolic parameters in high fat fed Wistar rats.

BACKGROUND: Limited data on adipose tissue zinc content in obesity exist. At the same time, the association between adipose tissue zinc content and metabolic parameters in dietary-induced obesity is poorly studied. Therefore, the primary objective of this study is to assess adipose tissue zinc content and its association  with morphometric parameters, adipokine spectrum, proinflammatory cytokines, and apolipoprotein profile in high fat fed Wistar rats. METHODS: A total of 48 adult female Wistar rats were used in the present study. Rats were fed either control (10% of fat) or high fat diet (31.6% of fat). Adipose tissue zinc content was assessed using inductively coupled plasma mass spectrometry. Rats' serum was examined for adiponectin, leptin, insulin, interleukin-6, and tumor necrosis factor-α using enzyme-linked immunosorbent assay kits. Serum glucose and apolipoprotein spectrum were also evaluated. RESULTS: High fat feeding resulted in a significant 34% decrease in adipose tissue zinc content in comparison to the control values. Fat pad zinc levels were significantly inversely associated with morphometric parameters, circulating leptin, insulin, tumor necrosis factor-α levels and HOMA-IR values. At the same time,      a significant correlation with apolipoprotein A1 concentration was observed. CONCLUSIONS: Generally, the obtained data indicate that (1) high fat feeding results in decreased adipose tissue zinc content; (2) adipose tissue zinc content is tightly associated with excessive adiposity, inflammation, insulin resistance and potentially atherogenic changes.

Zinc asparaginate supplementation induces redistribution of toxic trace elements in rat tissues and organs.

The primary objective of the current study was the investigation of the influence of zinc asparaginate supplementation for 7 and 14 days on toxic metal and metalloid content in rat organs and tissues. Rats obtained zinc asparaginate in doses of 5 and 15 mg/kg/day for 7 and 14 days. At the end of the experiment rat tissues and organs (liver, kidney, heart, m. gastrocnemius, serum, and hair) were collected for subsequent analysis. Estimation of Zn, Al, As, Li, Ni, Sn, Sr content in the harvested organs was performed using inductively coupled plasma mass spectrometry at NexION 300D. The obtained data showed that intragastric administration of zinc significantly increased liver, kidney and serum zinc concentrations. Seven-day zinc treatment significantly affected the toxic trace element content in the animals' organs. Zinc supplementation significantly decreased particularly liver aluminium, nickel, and tin content, whereas lead tended to increase. Zinc-induced changes in kidney metal content were characterized by elevated lithium and decreased nickel concentration. Zinc-induced alteration of myocardical toxic element content was multidirectional. Muscle aluminium and lead concentration were reduced in response to zinc supplementation. At the same time, serum and hair toxic element concentrations remained relatively stable after 7-day zinc treatment. Zinc asparaginate treatment of 14 days significantly depressed liver and elevated kidney lithium content, whereas a significant zinc-associated decrease was detected in kidney strontium content. Zinc supplementation for 14 days resulted also in multidirectional changes in the content of heart toxic elements. At the same time, significant zinc-associated decrease in muscle lithium and nickel levels was observed. Fourteen-day zinc treatment resulted in significantly increased serum arsenic and tin concentrations, whereas hair trace element content remained relatively stable. Generally, the obtained data indicate a significant redistribution of toxic metals in the animal organism under zinc supplementation.

Effect of short-term zinc supplementation on zinc and selenium tissue distribution and serum antioxidant enzymes.

BACKGROUND: A significant association between Zn and Se homeostasis exists. At the same time, data on the influence of zinc supplementation on selenium distribution in organs and tissues seem to be absent. Therefore, the primary objective of the current study is to investigate the influence of zinc asparaginate supplementation on zinc and selenium distribution and serum superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity in Wistar rats. METHODS: 36 rats were used in the experiment. The duration of the experiment was 7 and 14 days in the first and second series, respectively. The rats in Group I were used as the control ones. Animals in Groups II and III daily obtained zinc asparaginate (ZnA) in the doses of 5 and 15 mg/kg weight, respectively. Zinc and selenium content in liver, kidneys, heart, muscle, serum and hair was assessed using inductively coupled plasma mass spectrometry. Serum SOD and GPx activity was analysed spectrophotometrically using Randox kits. RESULTS: Intragastric administration of zinc asparaginate significantly increased liver, kidney, and serum zinc content without affecting skeletal and cardiac muscle levels. Zinc supplementation also stimulated selenium retention in the rats' organs. Moreover, a significant positive correlation between zinc and selenium content was observed. Finally, zinc asparaginate treatment has been shown to modulate serum GPx but not SOD activity. CONCLUSIONS: The obtained data indicate that zinc-induced increase in GPx activity may be mediated through modulation of selenium status. However, future studies are required to estimate the exact mechanisms of zinc and selenium interplay.