Time dependent changes in oxidative metabolism during chronic diabetes in rats

The stability and capacity of antioxidant status during chronic diabetes seriously influence the outcome of the long-term complications caused by oxidative stress. In the present study we investigated the effects of chronic streptozotocin-induced diabetes on the parameters of antioxidant status: activity of scavenging enzymes, gluthation-related and total antioxidant capacity, and degree of lipid peroxidation. Changes in the activities of superoxide-dismutase (SOD), glutathione peroxidase (GSH-Px), gluthatione reductase (GSH-R), and catalase, and in the content of reduced gluthation (GSH), and oxidised gluthatione (GSSG), and in the ratio of GSH/GSSG in blood samples were determined by means of biochemical methods. The degree of lipid peroxidation was measured via thiobarbituric acid assay (TBARS). Hyperglycaemia, ketosis and the accumulation of glycated proteins were estimated by measuring blood glucose, 3-OH-butirate, fructosamine and haemoglobin A1C. In the course of chronic insulin-dependent diabetes, i.e. at 2 and 7 days, 10 weeks, and 6 and 8.5 months after streptozotocin injection, hyperglycaemia slightly while ketosis markedly attenuated. Lipid peroxidation was also attenuated. SOD activity decrease in the acute phase only. The activity of GSH-Px increased in the early phase while that of GSH-R mostly decreased in the chronic phase. GSH and GSSG concentrations moved into opposite direction in a time dependent manner. In conclusion, in chronic diabetes an attenuation of severity of diabetes was present throughout the post-injection period, which was well reflected in the improved antioxidant status and capacity

A tápanyagfelvétel és az energia-háztartás neuroendokrin szabályozása = Neuroendocrine regulation of nutrition and energy homeostasis

Az elhízás epidemiológiai súlya egyre nyomasztóbb a társadalomban. Eredmények: 1) Vizsgálták az obezitogén és antiobezitogén környezeti hatásokat a magzati egyedfejlődés során. A többszörösen telítetlen zsírsavak (PUFA-k) metabolikus programozó hatását igazolták. Döntően az n-3 PUFA hiány a fejlődés során olyan kórélettani hatásokat produkált, ami a gyermekkori elhízás modelljének is megfelel: inzulin rezisztencia, csökkent glukóz tolerancia, csökkent leptin érzékenység, fokozott zsírlerakódás. A PUFA többlet, ezzel ellentétesen, csökkentette a vér inzulin és leptin szinteket, csökkent a vér triglicerid és nőtt a HDL koleszterin mennyiség, javult a glukóz tolerancia. Néhány metabolikus hatás és a javuló kognitív teljesítmény még öregkorban is kimutatható volt. 2) A táplálék felvétel és az energia háztartás hypothalamikus szabályozásának vizsgálata során kimutatták, hogy kolinerg neuronok találhatók a n. arcuatusban, melyek orexigén támogató hatásukat az M3-as receptoron fejtik ki. M3 receptor antagonistával a neurogén elhízás kivéghető. Továbbá valószínű, hogy a hypothalamikus kolinerg rendszer szerepet játszik a vízfelvétel szabályozásában is. 3) Magatartási szelekcióval előidézett, epigenetikailag rögzült fokozott fizikai aktivitás egerekben olyan anyagcsere változásokat hozott létre, melyek megakadályozták a zsírdús diéta által kiváltott elhízást. Konklúzió: az elhízás prevenciója mind genetikai, mind környezeti hatások szempontjából megvalósíthatónak számít. | The epidemiologic burden of obesity extensively risks the health of society. Aims and results: 1) The obesitogenic and antiobesitogenic environmental factors during fetal development were investigated. The programming action of poly-unsaturated fatty acids (PUFAs) has been proven. PUFA deficient diet produced symptoms characteristic to childhood obesity: insulin resistance, decreased glucose tolerance, decreased leptin sensitivity, increase fat deposition. Contrary, PUFA supplementation decreased blood insulin, leptin and triglycerides levels, increased HDL cholesterol and glucose tolerance. Some metabolic effects and the improved cognitive performance lasted up to old ages. 2) Interaction between peptidergic and classical (cholinerg) neurotransmitter systems was also studied in the regulation of food intake and energy metabolism. Cholinerg neurons have been found in the n. arcuatus, which exert orexigen support on MCH neurons through M3 receptors and markedly influence water intake as well. M3 antagonist 4-DAMP prevented neurogen obesity induced by SHU9119. 3) Interaction between nutrition and physical activity studies showed that mice selected for high running wheel activity showed profound antiobesitogenic metabolic changes and consequent resistance against diet induced obesity. Summary: the results showed that obesity prevention can be supported by both genetic and environmental interventions in the course of development

Aging of the brain

An increasing number of persons live for nine or more decades and enjoy the benefits of a well-functioning brain until the end of their life. In that respect, the cognitive performance in later life and the quality maintenance of the brain are amazing biological phenomena. Since most nerve cells are generated during pregnancy and have to survive an active lifetime, the brain has to be endowed with a maintenance machinery of surprising long-term quality. During successful, that is, non-pathological, aging in most brain regions, there is very little or no evidence for a decrease in numbers of neurons. In some brain structures, a limited reduction of nerve cells may occur, but it is generally conceived that aging and aging-related cognitive impairments are not the result of massive cell loss but rather the result of synaptic changes, receptor dysfunction or signaling deficits, and metabolic decline. Besides, nerve cell loss during normal aging may be compensated by synaptogenesis, dendritic branching, or in certain brain structures like dentate gyrus by neurogenesis from progenitor stem cells. Yet most human individuals suffer from a mild but life-disturbing condition we call agingrelated memory impairment (AMI). In this chapter, some of the mechanisms will be shortly explored that are considered to be causal to non-pathological deterioration of cognitive faculties. In particular several cellular and molecular neuronal changes will be addressed that occur during aging, the consequences for interneuronal communication and membrane potential, the blood supply to the brain and cerebrovascular condition, and some observations on the protective neuroimmune system of the brain

A novel method for evaluating microglial activation using ionized calcium-binding adaptor protein-1 staining:cell body to cell size ratio

Aim: The aim was to validate a newly developed methodology of semi-automatic image analysis to analyze microglial morphology as marker for microglial activation in ionized calcium-binding adaptor protein-1 (IBA-1) stained brain sections. Methods: The novel method was compared to currently used analysis methods, visual characterization of activation stage and optical density measurement, in brain sections of young and aged rats that had undergone surgery or remained naοve. Results: The cell body to cell size ratio of microglia was strongly correlated to the visual characterization activation stage. In addition, we observed specific surgery and age-related changes in cell body size, size of the dendritic processes and cell body to cell size ratio. Conclusion: The novel analysis method provides a sensitive marker for microglial activation in the rat brain, which is quick and easy to perform and provides additional information about microglial morphology

Temporal and spatial dynamics of corticosteroid receptor down-regulation in rat brain following social defeat

The experiments explored the nature and time course of changes in glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) binding in homogenates of various brain regions and pituitary of male Wistar rats following social defeat stress. One week after defeat, the binding capacity of GRs was decreased in the hippocampus and the hypothalamus while no changes were observed in the parietal cortex and the pituitary. The number of MRs remained at the same level as in undefeated rats. Three weeks postdefeat, the initially down-regulated GR returned to baseline level in the hippocampus and the hypothalamus. However, GR binding was now decreased in the parietal cortex. Severe down-regulation of MRs was detected in the hippocampal and septal tissue. The results show that brief but intense stress like social defeat induces a long-lasting down-regulation of corticosteroid receptors and that the temporal dynamics of these changes are not only differential for GRs and MRs but also for brain sites.

The basal forebrain cholinergic system in aging and dementia:Rescuing cholinergic neurons from neurotoxic amyloid-beta 42 with memantine

The dysfunction and loss of basal forebrain cholinergic neurons and their cortical projections are among the earliest pathological events in the pathogenesis of Alzheimer's disease (AD). The evidence pointing to cholinergic impairments come from studies that report a decline in the activity of choline acetyltransferase (ChAT) and acetylcholine esterase (AChE), acetylcholine (ACh) release and the levels of nicotinic and muscarinic receptors, and loss of cholinergic basal forebrain neurons in the AD brain. Alzheimer's disease pathology is characterized by an extensive loss of synapses and neuritic branchings which are the dominant scenario as compared to the loss of the neuronal cell bodies themselves. The appearance of cholinergic neuritic dystrophy, i.e. aberrant fibers and fiber swelling are more and more pronounced during brain aging and widely common in AD. When taking amyloid-beta (A beta) deposition as the ultimate causal factor of Alzheimer's disease the role of A beta in cholinergic dysfunction should be considered. In that respect it has been stated that ACh release and synthesis are depressed, axonal transport is inhibited, and that ACh degradation is affected in the presence of A beta peptides. beta-Amyloid peptide 1-42, the principal constituent of the neuritic plagues seen in AD patients, is known to trigger excess amount of glutamate in the synaptic cleft by inhibiting the astroglial glutamate transporter and to increase the intracellular Ca(2+) level. Based on the glutamatergic overexcitation theory of AD progression, the function of NMDA receptors and treatment with NMDA antagonists underlie some recent therapeutic applications. Memantine, a moderate affinity uncompetitive NMDA receptor antagonist interacts with its target only during states of pathological activation but does not interfere with the physiological receptor functions. In this study the neuroprotective effect of memantine on the forebrain cholinergic neurons against A beta 42 oligomers-induced toxicity was studied in an in vivo rat dementia model. We found that memantine rescued the neocortical cholinergic fibers originating from the basal forebrain cholinergic neurons, attenuated microglial activation around the intracerebral lesion sides, and improved attention and memory of A beta 42-injected rats exhibiting impaired learning and loss of cholinergic innervation of neocortex. (C) 2010 Elsevier B.V. All rights reserved

Examination between the measured and estimated parameters of the participants in the Hungarian Defence Forces Body Composition Program

Introduction: The aim of the research was to analyze the - Introduced in 2015 as a new force protection capability - Hungarian Defence Forces Body Composition Program (HDF BCP) participants’ pattern of the measurement parameters and their relationship to each other, furthermore, to create a measurement protocol that can be used with large number of elements, which allows the estimation of strength and fat-free mass in the following.Methods: The examination was carried out between 2017 and 2020. Within the HDF BCP, the measured and estimated parameters of 283 volunteers between the ages of 18 and 67 years old. A total of 709 measures were made. A Premium Body Impedance Analyzer 500 (BIA) instrument was used for the examinations. In addition, a DYNA 16 strength meter (DYNA) was used which makes it possible to measure the grip strength of both hands at the same time. Statistical calculations are performed with R-Studio program.Results: An increase in the phase angle is accompanied by an increase in the maximum hand grip strength (p < 0.001). The full body strength increases with weight gain regarding both sexes in all age groups tested (p < 0.001). Our linear regression model is suitable for estimating maximum hand grip strength using body weight, fat-free mass, age, and gender values (R2 = 0,74) and to estimate fat-free mass percentage based on body weight, maximum hand grip strength, and gender values (R2 = 0,78).Conclusion: The use of phase angle is an important indicator of a lifestyle change program. In the created linear regression model we will be able to estimate body fraction in significant numbers with high accuracy after measuring minimum parameters