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We studied the effect of human lactoferrin on cells of the hippocampal dentate gyrus of 2-2.5-month-old male C57BL/6 mice after acute gamma irradiation of the head in a dose of 8 Gy from a 60 Co source. Immediately after irradiation some animals received an intraperitoneal injection of human lactoferrin (4 mg/mouse). The appearance of TUNEL + cells in the subgranular zone 6 h after irradiation was accompanied by a corresponding decrease in the number of Ki-67- and DCX-immunoreactive cells. Administration of lactoferrin had a protective effect on mouse brain cells, which manifested in a decrease in the number of TUNEL + cells (by 77% relative to the irradiation alone) and an increase in the number of proliferating cells (from 16 to 61% relative to control animals) and immature neurons (from 14 to 22% relative to control animals) in the dentate gyrus of the hippocampus., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Lactoferrin (Lf) is a multifunctional protein from the transferrin family. Of particular interest is the ability of Lf to affect a wide range of neuronal processes by modulating the expression of genes involved in long-term neuroplasticity. The expression of the immediate early gene c-fos that is rapidly activated in response to external influences, and its product, transcription factor c-Fos, is widely used as a marker of long-term neuronal plasticity. The present study aims to examine the effect of human Lf on the induction of transcription factor c-Fos in the primary mouse neuronal cultures after stimulation and to determine the cellular localization of human Lf and its colocalization with induced c-Fos protein. Primary dissociated cultures of hippocampal cells were obtained from the brains of newborn C57BL/6 mice (P0-P1). On day 7 of culturing, human Lf was added to the medium. After 24 h (day 8 in culture), c-Fos protein was induced in cells by triple application of 50 mM KCl. c-Fos content was analyzed using the immunofluorescent method 2 h after stimulation. Stimulation promoted exogenous Lf translocation into the nuclei of cultured neuronal cells, which correlated with increased induction of transcription factor c-Fos and was accompanied by nuclear colocalization of these proteins. These results attest to the potential of Lf as a modulator of neuronal processes and open up new prospects in studying the mechanisms of the regulatory effects of lactoferrin on cell function.

Newly hatched domestic chicks are known to orient preferentially toward naturalistic stimuli, resembling a conspecific. Here, we examined to what extent this behavioral preference can be transcended by an artificial imprinting stimulus in both short-term and long-term tests. We also compared the expression maps of the plasticity-associated c-fos gene in the brains of chicks imprinted to naturalistic (rotating stuffed jungle fowl) and artificial (rotating illuminated red box) stimuli. During training, the approach activity of chicks to a naturalistic object was always higher than that to an artificial object. However, the induction of c-fos mRNA was significantly higher in chicks imprinted to a box than to a fowl, especially in the intermediate medial mesopallium, hyperpallium apicale, arcopallium, and hippocampus. Initially, in the short-term test (10 min after the end of training), chicks had a higher preference for a red box than for a stuffed fowl. However, in the long-term test (24 h after imprinting), the response to an artificial object decreased to the level of preference for a naturalistic object. Our results thus show that despite the artificial object causing a stronger c-fos novelty response and higher behavioral attachment in the short term, this preference was less stable and fades away, being overtaken by a more stable innate predisposition to the naturalistic social object., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cherepov, Tiunova and Anokhin.)

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 60 Co 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.

Indicators of the cardiovascular system, including heart rate (HR) and blood pressure (BP) variability parameters, were analyzed in primary school students with different computer screen times. The study included 4084 students of grades 1-4 (age 7-12 years) from 66 Moscow schools. The screen time at school and out of school was assessed by teachers, based on the national Sanitary Rules and Regulations: 0, no screen time; 1, screen time matching hygienic standards; 2, screen time at least twice greater than recommended. Physiological examinations were carried out by spiroarteriocardiorhythmography with a face mask, the conditions corresponding to the functional stress test (mild hypercapnia/hypoxia). Testing took place in spring and autumn (independent samples). Statistical data processing was performed using nonparametric criteria. It was revealed that the introduction of computer technologies in school lessons within the limits of hygienic standards was accompanied by an increase, within the normal range, of systolic BP in girls at the end of grade 2 and 4 and in boys at the beginning and end of grade 4. Screen time at least twice higher than the hygienic standard did not have an additional effect on BP, but provoked shifts in the function of autonomic regulation. Boys were more sensitive to the influence of this environmental factor. Their pattern of seasonal variability in total power (TP) of the HR variability spectrum was reversed compared to that of children who did not use computers at school; i.e., higher TP values were observed in spring. In grade 4, the process was accompanied by an increase in spontaneous arterial baroreflex sensitivity and a decrease in the relative power of the LF range in the variability spectrum of systolic BP. The changes were assumed to reflect the adaptive response to changes in educational environment., Competing Interests: CONFLICT OF INTERESTThe authors declare that they have no real or potential conflict of interest. Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the 1964 Helsinki Declaration and its later amendments and applicable Russian laws on the legal and ethical principles of research and were approved by the Ethics Committee at the Institute of General Pathology and Pathophysiology (Moscow; Minutes no. 1 dated January 22, 2019). In compliance with Articles 5, 6, and 7 of the Universal Declaration on Bioethics and Human Rights, all studies were only performed with consent from students and their parents (or legal representatives)., (© The Author(s) 2021, ISSN 0362-1197, Human Physiology, 2021, Vol. 47, No. 6, pp. 628–638. © The Author(s), 2021. This article is an open access publication.Russian Text © The Author(s), 2021, published in Fiziologiya Cheloveka, 2021, Vol. 47, No. 6, pp. 43–55.)

We studied the effect of human lactoferrin (hLf) on degenerative changes in the nigrostriatal system and associated behavioral deficits in the animal model of Parkinson disease. Nigrostriatal dopaminergic injury was induced by single administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 40 mg/kg) to five-month-old C57Bl/6 mice. Behavioral disturbances were assessed in the open field and rotarod tests and by the stride length analysis. Structural deficits were assessed by the counts of tyrosine hydroxylase (TH)-immunoreactive neurons in the substantia nigra and optical density (OD) of TH-immunolabeled fibers in the striatum. Acute MPTP treatment induced long-term behavioral deficit and degenerative changes in the nigrostriatal system. Pretreatment with hLf prevented body weight loss and promoted recovery of motor functions and exploratory behavior. Importantly, OD of TH-positive fibers in the striatum of mice treated with hLf almost returned to normal, and the number of TH-positive cells in the substantia nigra significantly increased on day 28. These results indicate that hLf produces a neuroprotective effect and probably stimulates neuroregeneration under conditions of MPTP toxicity in our model. A relationship between behavioral deficits and nigrostriatal system disturbances at delayed terms after MPTP administration was found.

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., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

We studied different ways of transport of human lactoferrin to the brain of C57Bl/6 mice after its administration via different routes, analyzed its distribution in the brain, and determined the phenotype of lactoferrin-containing cells. Colocalization of lactoferrin and markers of various cell types was estimated by fluorescent immunohistochemical analysis. Lactoferrin was detected in mouse brain sections after its intranasal, sublingual, and intraperitoneal administration, but not after conjunctival administration. After intranasal administration, lactoferrin rapidly penetrated into the brain and accumulated in the cytoplasm of vascular endothelial cells in the neocortex, striatum, hippocampus, and thalamus. After application of protein solution onto fixed floating sections, highly specific binding of lactoferrin was found in the nuclei of neurons, astrocytes, and microglia cells, but not in the nuclei of endothelial cells of mouse brain.

We reproduced mouse model of bronchial asthma, evaluated metabolic shifts of serum homeostasis during disease development, and compared these results with the data on metabolic shifts in bronchial asthma patients. In experimental mice pronounced pathological changes in the lungs, considerable lymphocytosis and decrease in neutrophil count were detected. Metabolic shifts were studied using method of laser correlation spectroscopy (LCS) of blood serum and urine. Method of LCS allows determining the dispersion composition of the studied fluid by the relative contribution of particle components into light scattering. The relative content of particles of different size.characterizes the direction of metabolic shifts in the organism. Similar patterns of particle distribution in biological fluids of experimental animals and patients suggest that LCS can be used as an additional method for evaluation of the severity of the disease and efficiency of therapy.

We studied radiosensitivity of 101/Hf, C3H/Sn, and C57Bl mice exposed to sublethal doses of γ-radiation. C57Bl mice responded to radiation much later than 101/Hf and C3H/Sn mice, while their adaptability was high enough. 101/Hf and C3H/Sn mice developed acute radiation sickness in a similar way. However, C3H/Sn mice showed better physiological indicators after radiation crisis. There was no noticeable improvement after the development of radiation sickness in 101/Hf mice. To assess individual radiosensitivity, integrated approach should be applied using the data obtained by different methods on several physiological levels.

The effects of TRAIL at various physiological levels were studied on 101/Hf and C3H/Sn mice during acute γ-irradiation with 750 R. An intravenous injection of TRAIL attenuated the effects of γ-irradiation on the body weight, subfractions of blood plasma, horizontal and vertical activity in the open-field test, tissue injury in the small intestine and liver, and content of Hassall's corpuscles in the thymus. The degree of these changes differed in mice of study strains.

The cytotoxic effects of human blood serum were studied under normal and pathological conditions. The contribution of the complement system to the realization of this effect was demonstrated. Significant differences in the serum capacity to kill foreign cells were detected for healthy subjects and asthmatics. Bovine sperm suspension can serve as the test object for rapid evaluation of functional activity of the complement system.

Effects of the psychostimulants D-amphetamine and sydnocarb on the locomotor activity and c-Fos protein expression in the brain of C57BL and BALB/c mice was studied. The drugs significantly increase the locomotor activity and the level of c-Fos protein in the brain structures of both lines. The effect of D-amphetamine with respect to the locomotor activity was more pronounced in C57BL mice, which correlates with a higher level of the c-Fos expression in the secondary motor cortex. At the same time syndocarb more significantly than D-amphetamine induces expression of the c-Fos protein in the nucleus accumbens core of C57BL mice. Injection of an 0.85% NaCl solution led to a moderate increase in the locomotor activity in the mice of both lines, while the c-Fos expression in the secondary motor cortex and septum was more pronounced in C57BL than in BALB/c mice.