The effect of constant illumination as a stress factor on the state of the "early response" c-fos gene in the lateral magnocellular subnuclei of the paraventricular nucleus (lmPVN) of the hypothalamus of rats at different time intervals (day and night) has been studied. To identify c-Fos in histological sections of the hypothalamus, a secondary (indirect) immunofluorescence method is used. Expression of the product of this gene, the c-Fos protein, in animals kept under normal conditions of alternation of illumination and darkness, shows a clear-cut circadian character. There was a significant decrease in the area of the immunopositive sites of structures at night by 19.4% compared to daytime measurements. The average values of the areas of such immunopositive subnuclei sites varied also in subgroups of rats under light stimulation conditions, in which samples of lmPVN were selected for study at 2 pm and 2 am, but the differences between groups did not reach the level of reliability. Under conditions of light stress, the c-Fos concentration index decreased by 29.4% during the day, and by 16.5% at night in relation to similar values in the intact group. In animals that were in the standard light mode, the c-Fos protein concentration index was significantly higher during the day than at night. In the intact group, the night value of the c-Fos concentration index averaged only 71.5% of the daily value. In rats subjected to constant illumination, the day and night values of the c-Fos concentration index did not differ reliably. To correct stress-induced changes in the activity of the "early response" c-fos gene in the rat hypothalamus, melatonin (0.5 mg/kg body weight of the animal) was used. Injections of melatonin to rats exposed to constant illumination normalized the circadian rhythm of the area of the material immunoreactive to c-Fos, compared to the group of animals that did not receive melatonin. When using melatonin against the background of constant illumination, a sharp increase of the protein concentration in the lmPVN subnuclei of hypothalamus in daytime and less pronounced at night intervals was detected. Injections of melatonin to animals were also reflected in the daily dynamics of the index of c-Fos protein content in the lmPVN subnuclei under conditions of constant illumination. In the daytime observation period, the index was almost twice the experimental data on stressed animals without the introduction of the hormone, bringing it closer to normal. Prospects for further research in this sphere will allow us to better understand the place and role of subnuclei of paraventricular nuclei of the hypothalamus in the mechanisms of the formation of circadian rhythms of the rat brain.
Introduction. Melatonin production is considerably suppressed by light and affects the ability to transfer daily rhythm information from the hypothalamus to other neural target sites and thus alters the expression of some biological rhythms. The hormone controls the state of the hypothalamic-pituitary system and endocrine gland activity through melatonin receptors (membrane, cytosolic and nuclear ones). In addition, using a mechanism of the feedback, it interferes with the activity of supraoptic nucleus of the hypothalamus, which regulates water-salt metabolism and responses to stress. Objective: to provide quantitative circadian characteristics of melatonin receptors density in the neurons of the hypothalamic supraoptic nucleus of rats being under light stimulation as well as the correction of changes after injecting exogenous melatonin. Material and methods. The experiments were conducted on 60 white mongrel mature male rats weighing 150 – 180 g. The test animals were divided into 3 parts each with 2 groups, kept under the conditions of standard light regime, hyperilluminated and the injection of exogenous melatonin and day-round lighting within 7 days. To perform immunohistochemical methods, we used polyclonal antibodies to melatonin 1A receptors produced by Abcam and streptavidin biotin visualization system LSAB2 (peroxidase mark + diaminobenzidine) produced by Chemicon International Inc. We adhered to protocol standardization of methods for all sections. Additional staining of nuclei was performed with Mayer hematoxylin. Results. The indices of optical density of specific melatonin 1A receptors of supraoptic neurocytes staining obtained in the intact group (at 02.00 AM- 0,488 ± 0,0024, at 02.00 P.M. - 0,464 ± 0,0023, p = 0.002) and in animals subjected to light stress (at 02.00 AM-0,295 ± 0, 0019, at 02.00 P.M.- 0,286 ± 0,0018, p = 0,012) had a probable value and were characterized by a clear diurnal periodicity. In the group of animals with pineal gland hypofunction modulation (at 02.00 A.M.- 0,216 ± 0,0017, at 02.00 P.M. - 0,214 ± 0,0021, p> 0,05). Conclusions The density of 1A melatonin receptors in rat’s hypothalamic supraoptic neurons are normally characterized by an accurate circadian rhythm. The highest density of receptors is observed at 02.00 AM, and at 02.00 PM it is significantly lower (p = 0.002). Immunohistochemical studies revealed that under inhibition of pineal gland activity the circadian rhythm of melatonin receptors density in neurons of supraoptic nuclei of the hypothalamus gets disturbed, which is characterized by an incredible difference of indices in the tested periods of the day.
The aim: Was to study enalapril effect on protein peroxide oxidation and lipids of the cerebral cortex and hippocampus of rats with neurodegeneration pattern. Materials and methods: The experiments were conducted on nonlinear albino male rats 0,18-0,20 kg of the body weight. Modeled neurodegeneration was simulated by intraperitoneal introduction of scopolamine hydrochloride during 27 days in the dose of 1 mg/kg. Enalapril was introduced intraperitoneal in the dose of 1 mg/kg. Results: In rats with modeled scopolamine-induced neurodegeneration in the cerebral cortex and hippocampus under enalapril effect, the content of products, reacting with 2-thiobarbituric acid and proteins of a neutral and major character, decreases, which is indicative of a reduced intensity of lipid and protein peroxide oxidation. Morphologic the number of cells with karyopyknosis signs decreases and a relative staining density of the neuron tigroid substance increases, which is indicative of inhibition of the progress of the cerebral neurodestructive processes under conditions of scopolamine-induced damage. Conclusions: The obtained results are indicative of enalapril ability to improve the examined indices, which is the evidence of increased processes of antioxidant protection and possibility to inhibit neurodegeneration development in case of scopolamine induced lesion of the brain.
A progressive increase of complications of type 2 DM makes the problem very important for clinical andfundamental medicine. In particular, neurodegenerative processes in case of type 2 DM aggravate the courseof the disease, change a usual life rhythm, and are a valuable cause of high rates of disability and lethality.Deterioration of cognitive functions is one of the main complications of diabetes. In certain literary sourcesinhibitors of angiotensin-transforming enzyme are considered as the means to prevent and treat complicationsof diabetes mellitus. Their role as modulators of gama-aminobutyric acid with development of central diabeticneurodegeneration is not completely determined yet.Therefore, the objective of the study is to assess efficacy of pharmacological correction of cognitive disordersby carbacetam, a GABA modulator, and enalapril, a RAS blocker, in case of experimental neurodegenerationcaused by type 2 DM.Changes of the cognitive functions under carbacetam and enalapril effect in nonlinear laboratory albinomale rats with neural degeneration under conditions of type 2 diabetes mellitus simulated by streptozotocin andhigh fat diet are studied. The cognitive ability was assessed by behavioral reactions of rats in the tests «openfield» and «the conditional reflex reaction of passive avoidance» by Butler formula.Behavior of rats with type 2 diabetes mellitus after administration of carbacetam and enalapril showed ofcognitive functions in the groups. At the same time, carbacetam was found to possess better correcting effect onadaptation, cognitive reactions and anti-amnestic activity, while enalapril improved emotional condition of therats mostly. Analysis of anti-amnestic properties found higher values of the parameters on the 14th day than onthe 1st day of correction, which is indicative of the efficacy of a course administration of carbacetam and enalapril under conditions of neural degeneration stipulated by type 2 DM.
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