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INTRODUCTION: The neuronal cell death associated with perinatal anoxia plays a significant role in neonatal morbidity and neurodevelopmental disability. In response to mild stress, a number of compensatory mechanisms are activated, which allows the cells to survive. Beside decreased body temperature, brain-derived neurotrophic factor (BDNF) is also considered to be beneficial to neuronal survival. AIM(S): Therefore, the aim of this study was to determine whether body temperature under anoxic condition affects the ability of BDNF (proBDNF and mBDNF) to decrease caspase‑3 levels in the developing brain. METHOD(S): 2-day-old Wistar rats were divided into 3 temperature groups: i) normothermic ‑33°C (typical body temperature of newborn rats), ii) hyperthermic – 37°C (typical body temperature of adult rat), and iii) extremely hyperthermic – 39°C (typical body temperature of febrile adult rats). The temperature was controlled starting 15 minutes before, and the measurement was continued during 10 minutes of anoxia (pure nitrogen atmosphere), as well as, for 2 hours postanoxia. Levels of BDNF and caspase-3 were determined post mortem, 2 and 72 hours after anoxia using Western blot and ELISA analysis. RESULTS: Body temperature affected the levels of endogenous BDNF, its precursor form (proBDNF), and caspase‑3. In anoxic animals, the levels of proBDNF and caspase-3 increased with increasing neonatal body temperature. In contrast, a significant negative correlation between the total BDNF to proBDNF ratio, and caspase-3 concentrations was observed. CONCLUSIONS: The results suggest that decreased body temperature can not only up-regulate BDNF levels, but also may affect the other functions of this neuropeptide. FINANCIAL SUPPORT: Research on this paper was supported by grant from National Science Centre, Poland, no. 016/21/N/NZ7/00399.
BACKGROUND AND AIMS: Complications after neonatal asphyxia are the most common cause of subsequent neurological disorders. The mechanism involved in brain damage is closely associated with abnormal iron metabolism that is a cofactor of free-radical reactions. There is a number of evidence that one of the endogenous processes that protect the brain from damage due to perinatal hypoxia is decreasing of body temperature. It is also known, that the transcriptional hypoxia-inducible factor1α (HIF-1α) plays the fundamental role in adaptive process in response to hypoxia. HIF-1α upregulates several genes involved in glycolysis, erythropoiesis, and angiogenesis to promote survival. Our experiments aimed at checking the effects of body temperature during simulated perinatal anoxia on the subsequent changes of  HIF-1α expression in brain. Considering the key role of iron as a cofactor of free radical reactions and it’s contribution in proteasomal degradation of α subunit of HIF protein, the second goal of the project was to verify the influence of deferoxamine (iron chelating agent) on the level of expression of HIF-1α in a variety of thermal conditions. METHODS: Two-day-old Wistar rats were divided into 4 temperature groups: (1) hypothermic (31°C), (2) normothermic (33°C), (3) hyperthermic typical to adult rats (37°C) and (4) hyperthermic typical to febrile adults rats (39°C). Within each group, infants were divided into two subgroups: animals with saline injection and animals with deferoxamine injection. The temperature was controlled starting 15 minutes before, and continuing during 10 minutes of anoxia (pure nitrogen atmosphere) as well as for 2 hours postanoxia. Levels of HIF-1α gene expression were analyzed post mortem: immediately, 3 and 7 days after anoxia using Western blot analysis. RESULTS: The results showed, that the body temperature during neonatal anoxia affects the level of HIF-1α expression. Moreover, the use of deferoxamine increases the expression of this gene.
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Effects of angiotensins II (AngII), angiotensin IV (AngIV, 3-8 fragment of angiotensin II) and losartan (an antagonist of angiotensin receptor type 1) on the proliferation of adrenocortical cells in ovariectomized rats have been studied. The incorporation of bromodeoxyuridine (BrdU) into cell nuclei was used as an index of cell proliferation. AngIV decreased BrdU labeling index mainly in the reticularis zone and losartan (Los) was able to partially reverse this inhibitory effect of AngIV. AngII had no effect on the adrenocortical cell proliferation when given alone, however Los given simultaneously diminished BrdU incorporation into nuclei of glomerulosa and reticularis zones as compared with AngII. These findings suggest that AngII and AngIV modulate adrenocortical cell proliferation in ovariectomized rats.
INTRODUCTION: An electromagnetic field is a factor that people are exposed to constantly, from various sources. Thus, the interest in its influence on living organisms increases. AIM(S): The aim of this work was to investigate the long‑term effects of an extremely low frequency electromagnetic field 50 Hz (ELF-EMF) on stress-related behaviour. METHOD(S): Adult male Wistar rats were exposed to ELF‑EMF of two values of magnetic induction: 1mT and 7mT. Animals were exposed to ELF‑EMF 1 or 8 hours a day for 7 days. Behavioral changes were evaluated in the open field test, which was performed in 1mT groups immediately or 5 weeks after the exposure, and in 7mT groups immediately, 5 weeks, and additionally 9 and 13 weeks after the exposure to ELF‑EMF. Control rats were subjected to the same experimental procedure as the respective animals exposed to ELF‑EMF except electromagnetic field exposure. We also included in the procedure the non‑treated and then exposed to the open field rats (sham). RESULTS: The behaviour of the animals exposed to 1mT did not differ significantly in comparison to control groups, regardless of the time of exposure. In 7mT groups, we found changes in stress behaviour and their intensity increased with increasing exposure time. In addition, the ELF-EMF-induced effect persisted longer in the case of the group exposed for 8 hours compared to animals exposed for 1 hour. CONCLUSIONS: On this basis, we concluded that ELF-EMF of 7mT may act as a stress factor, and its long‑lasting effects depend on the time of exposure. Furthermore, the absence of significant differences in the case of 1mT ELF‑EMF may indicate the existence of certain compensatory mechanisms in the organism, which allows them to avoid a negative influence of the weak electromagnetic filed. FINANCIAL SUPPORT: Research supported by grant from National Science Centre, Poland, no. 2017/25/B/ NZ7/00638 and project no. POWR.03.05.00‑00‑Z302/17 Universitas Copernicana Thoruniensis In Futuro, a part of the programme Knowledge Education Development.
INTRODUCTION: Complications after neonatal asphyxia are the most common cause of subsequent neurological disorders. Transcriptional hypoxia‑inducible factor‑1α (HIF‑1α) plays the fundamental role in adaptive processes in response to hypoxia. Moreover, the most crucial role in neuronal plasticity is attributed to brain-derived neurotrophic factor (BDNF). Newborn mammals showing reduced physiological body temperature are protected against perinatal asphyxia-induced neurotoxicity. The processes underlying neuroprotective effects of decreased body temperature might include the increased levels of HIF‑1α and BDNF. AIM(S): Therefore, we aimed at experimental verification of the hypothesis, that the body temperature during perinatal anoxia affects the level of HIF‑1α and BDNF. METHOD(S): Two-day-old newborn rats were exposed to anoxia in 100% nitrogen atmosphere for 10 min in different thermal conditions, which allow them to regulate the rectal temperature at the level of i. 33°C (physiological to rat neonates), ii. 37°C (level typical of healthy adult rats), or iii. 39°C (febrile adult rats). Hippocampal and cortex levels of HIF‑1α and BDNF were determined 1) immediately after anoxia, 2) 3 days after anoxia, and 3) 7 days after anoxia. RESULTS: There were no postanoxic changes in the level of BDNF in newborn rats kept at body temperature of 33°C. In contrast, at hyperthermic thermal conditions the level of the neurotrophin was decreased. Thermal conditions during neonatal anoxia affected the cerebral level of HIF‑1α. The highest level of anoxia‑induced HIF‑1α production was recorded in animals having physiological body temperature in comparison with that in hyperthermic animals. CONCLUSIONS: Since HIF-1 and BDNF have been recently regarded as promising therapeutical targets against brain lesions due to hypoxia/ischemia, presented data imply that to achieve a full effect of neuroprotection, the thermal conditions during and after the insult should be taken into consideration. FINANCIAL SUPPORT: Research on this paper was supported by grant from National Science Centre, Poland, no 2016/21/N/NZ7/00399.
INTRODUCTION: Over the last few decades, electromagnetic pollution from generated electromagnetic fields increases. Particularly important from the point of view of our health is the exposure to extremely low frequency electromagnetic fields (ELF‑EMF). ELF‑EMF is derived from many man-made sources, including power transmission lines or transformers. The effects induced by ELF-EMF exposure on biological systems are still unclear. AIM(S): Therefore, the aim of this study was to determine the long‑term consequences of 50 Hz ELF‑EMF of 1mT and 7mT on the noradrenaline level stress parameter in the rat brain. METHOD(S): 3-month-old male Wistar rats were divided into groups: 1) sham animals (directly taken from home cage; non‑treated), or 2) animals exposed to ELF‑MF (50 Hz, induction 1 mT or 7 mT). Animals were exposed to low (1 mT) or high density (7 mT) ELF‑EMF for one week, for 8h/day. Control animals were subjected to the same experimental procedure as the respective animals exposed to ELF-EMF except magnetic field exposure. The level of noradrenaline in the hypothalamus was measured using HPLC immediately and 5 weeks after the exposure in the group exposed to 1mT and in the group subjected to 7mT, additionally 9 and 13 weeks after the exposure. RESULTS: The results have shown that ELF-MF of both inductions (50 Hz) increased the level of noradrenaline in rats immediately after the exposure and the change in this hormone level was clear even 3 months later, but only in rats exposed to 7mT. CONCLUSIONS: In conclusion, our data indicated that ELF-MF changes noradrenaline levels in the rat brain. Changes found in the present study suggest that extremely low frequency electromagnetic fields could be considered as a stress factor and can be a cause of the development of stress‑related disorders. FINANCIAL SUPPORT: Research supported by project no. 2017/25/B/NZ7/00638 National Science Centre, Poland.
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