Nela Puškaš

The role of gut hormones in appetite regulation (review)

Eating process is an aggregate of complex and different forms of behavior. Its regulation is based on energy homeostasis and appetite control which includes two components: the homeostatic and the hedonistic control. Important signals in appetite regulation are gut-derived hormones. They are produced by enteroendocrine cells in response to nutrient and energy intake, and achieve their effects by influencing brain structures involved in food intake regulation. The key brain structure involved in this process is the hypothalamus. Gut hormones reach the hypothalamus from the circulation or by the vagal nerve via the nucleus of the solitary tract. Among gut peptides, ghrelin is the only orexigenic hormone, leading to an increase in food intake and body weight. All others, such as cholecystokinin, glucagon like peptide-1, oxyntomodulin, peptide tyrosine tyrosine or pancreatic polypeptide, are anorexigenic, leading to decrease in food intake. Also, gut-derived endocannabinoids exert orexigenic effect on appetite. Keeping in mind the growing problem of obesity, the crucial issue when considering gut derived peptides is to understand their mechanisms of acting because of potential role in clinical therapy, and discovering long-lasting gut peptides or their analogues, with no or minimal side effects.

Fractal analysis of dendrite morphology using modified box-counting method

The box-counting dimension of a non-stellate neuron changes continuously with its rotation. During preprocessing for box-counting, non-stellate neurons should be arranged so that the major diameters of their dendrite fields are parallel. A non-stellate neuronal picture should have the smallest fractal dimension when the angle between the horizontal axis and its major diameter is about 45°. The box-counting method does not consider the position of a picture on the computer screen. Therefore a dispersion of the box dimension values of a neuronal sample is rather large and their mean value is with larger variance. Modified box-counting method partly diminishes these findings. To improve a dependence of neuronal rotation on the box-counting dimension of non-stellate neurons, prior to applying box-counting method, non-stellate neurons should be arranged so that the major diameters of their dendrite fields are parallel.

Finasteride improves motor, EEG, and cellular changes in rat brain in thioacetamide-induced hepatic encephalopathy

Neurosteroids are involved in the pathogenesis of hepatic encephalopathy (HE). This study evaluated the effects of finasteride, inhibitor of neurosteroid synthesis, on motor, EEG, and cellular changes in rat brain in thioacetamide-induced HE. Male Wistar rats were divided into the following groups: 1) control; 2) thioacetamide-treated group, TAA (300 mg·kg(-1)·day(-1)); 3) finasteride-treated group, FIN (50 mg·kg(-1)·day(-1)); and 4) group treated with FIN and TAA (FIN + TAA). Daily doses of TAA and FIN were administered in three subsequent days intraperitoneally, and in the FIN + TAA group FIN was administered 2 h before every dose of TAA. Motor and reflex activity was determined at 0, 2, 4, 6, and 24 h, whereas EEG activity was registered about 24 h after treatment. The expressions of neuronal (NeuN), astrocytic [glial fibrilary acidic protein (GFAP)], microglial (Iba1), and oligodendrocyte (myelin oligodendrocyte glycoprotein) marker were determined 24 h after treatment. While TAA decreased all tests, FIN pretreatment (FIN + TAA) significantly improved equilibrium, placement test, auditory startle, head shake reflex, motor activity, and exploratory behavior vs. the TAA group. Vital reflexes (withdrawal, grasping, righting and corneal reflex) together with mean EEG voltage were significantly higher (P < 0.01) in the FIN + TAA vs. the TAA group. Hippocampal NeuN expression was significantly lower in TAA vs. control (P < 0.05). Cortical Iba1 expression was significantly higher in experimental groups vs. control (P < 0.05), whereas hippocampal GFAP expression was increased in TAA and decreased in the FIN + TAA group vs. control (P < 0.05). Finasteride improves motor and EEG changes in TAA-induced HE and completely prevents the development of hepatic coma.

Chronic stress, hippocampus and parvalbumin-positive interneurons: what do we know so far?

Abstract The hippocampus is a brain structure involved in the regulation of hypothalamic-pituitary-adrenal (HPA) axis and stress response. It plays an important role in the formation of declarative, spatial and contextual memory, as well as in the processing of emotional information. As a part of the limbic system, it is a very susceptible structure towards the effects of various stressors. The molecular mechanisms of structural and functional alternations that occur in the hippocampus under chronic stress imply an increased level of circulating glucocorticoids (GCs), which is an HPA axis response to stress. Certain data show that changes induced by chronic stress may be independent from the GCs levels, opening the possibility of existence of other poorly explored mechanisms and pathways through which stressors act. The hippocampal GABAergic parvalbumin-positive (PV+) interneurons represent an especially vulnerable population of neurons in chronic stress, which may be of key importance in the development of mood disorders. However, cellular and molecular hippocampal changes that arise as a consequence of chronic stress still represent a large and unexplored area. This review discusses the current knowledge about the PV+ interneurons of the hippocampus and the influence of chronic stress on this intriguing population of neurons.

Fractal dimension of apical dendritic arborization differs in the superficial and the deep pyramidal neurons of the rat cerebral neocortex

Pyramidal neurons of the mammalian cerebral cortex have specific structure and pattern of organization that involves the presence of apical dendrite. Morphology of the apical dendrite is well-known, but quantification of its complexity still remains open. Fractal analysis has proved to be a valuable method for analyzing the complexity of dendrite morphology. The aim of this study was to establish the fractal dimension of apical dendrite arborization of pyramidal neurons in distinct neocortical laminae by using the modified box-counting method. A total of thirty, Golgi impregnated neurons from the rat brain were analyzed: 15 superficial (cell bodies located within lamina II-III), and 15 deep pyramidal neurons (cell bodies situated within lamina V-VI). Analysis of topological parameters of apical dendrite arborization showed no statistical differences except in total dendritic length (p=0.02), indicating considerable homogeneity between the two groups of neurons. On the other hand, average fractal dimension of apical dendrite was 1.33±0.06 for the superficial and 1.24±0.04 for the deep cortical neurons, showing statistically significant difference between these two groups (p<0.001). In conclusion, according to the fractal dimension values, apical dendrites of the superficial pyramidal neurons tend to show higher structural complexity compared to the deep ones.

Quantification of structural changes in acute inflammation by fractal dimension, angular second moment and correlation.

The aim of the study was to examine alteration and possible application of fractal dimension, angular second moment, and correlation for quantification of structural changes in acutely inflamed tissue.

Behavioral and electroencephalographic manifestations of thioacetamide-induced encephalopathy in rats.

The aim of our study was to investigate the behavioral and electroencephalographic manifestations of thioacetamide-induced encephalopathy in rats. Male Wistar rats were divided among (i) control, saline-treated, and (ii) thioacetamide-treated groups (TAA(300) (300 mg/kg body mass); TAA(600) (600 mg/kg); and TAA(900) (900 mg/kg)). The daily dose of thioacetamide (300 mg/kg) was administered intraperitoneally once (TAA(300)), twice (TAA(600)), or 3 times (TAA(900)), on subsequent days. Behavioral manifestations were determined at 0, 2, 4, 6, and 24 h, while electroencephalographic changes were recorded 22-24 h after the last dose. General motor activity and exploratory behavior, as well as head shake, auditory startle reflex, placement, and equlibrium tests were diminished in the TAA(600) and TAA(900) groups compared with the control, and were absent in the TAA(900) group 24 h after treatment. Corneal, withdrawal, grasping, and righting reflexes were significantly diminished in the TAA(900) group compared with the control. Mean electroencephalographic power spectra density was significantly higher in TAA(300) and TAA(600) and lower in the TAA(900) group by comparison with the control. Only a score of 3 (mean dominant frequency ≤ 7.3 Hz and δ relative power ≥ 45%) was observed in the TAA(900) group. Thioacetamide induces encephalopathy in rats in a dose-dependent manner. A dose of 900 mg/kg TAA may be used as a suitable model of all stages of hepatic encephalopathy.

Hippocampal BDNF in physiological conditions and social isolation

Abstract Exposure of an organism to chronic psychosocial stress may affect brain-derived neurotrophic factor (BDNF) expression that has been implicated in the etiology of psychiatric disorders, such as depression. Given that depression in humans has been linked with social stress, the chronic social stress paradigms for modeling psychiatric disorders in animals have thus been developed. Chronic social isolation in animal models generally causes changes in hypothalamic-pituitary-adrenal axis functioning, associated with anxiety- and depressive-like behaviors. Also, this chronic stress causes downregulation of BDNF protein and mRNA in the hippocampus, a stress-sensitive brain region closely related to the pathophysiology of depression. In this review, we discuss the current knowledge regarding the structure, function, intracellular signaling, inter-individual differences and epigenetic regulation of BDNF in both physiological conditions and depression and changes in corticosterone levels, as a marker of stress response. Since BDNF levels are age dependent in humans and rodents, this review will also highlight the effects of adolescent and adult chronic social isolation models of both genders on the BDNF expression.

Modified Richardson's method versus the box-counting method in neuroscience

BACKGROUND The morphology of dendrites, including apical dendrites of pyramidal neurons, is already well-known. However, the quantification of their complexity still remains open. Fractal analysis has proven to be a valuable method of analyzing the degree of complexity of dendrite morphology. NEW METHOD Richardsons method is a technique of measuring the fractal dimension of open and closed lines of objects. This method was modified in order to measure the fractal dimension of neuronal arborization. The focus of this experiment was on the apical dendrites of superficial and deep pyramidal neurons in the rat cerebral cortex. RESULTS Apical dendrites of superficial cortical pyramidal neurons have a higher mean value of the fractal dimension as compared to deep pyramidal neurons. COMPARISON WITH EXISTING METHOD Using the modified Richardsons method we showed that the mean value of the fractal dimension of apical dendrites in superficial pyramidal neurons is highly statistically significant as compared to the value of the fractal dimension in deep pyramidal neurons. On the other hand, the mean values of the fractal dimension between the same groups of apical dendrites measured by the most popular box-counting method showed merely a statistically significant difference. CONCLUSION The modified Richardsons method of fractal analysis is an efficient mathematical method for calculating the fractal dimension of dendrites and could be used in order to calculate the complexity of dendrite arborization.

Fractal analysis of dendrites morphology using modified Richardson's and box counting method.

Fractal analysis has proven to be a useful tool in analysis of various phenomena in numerous naturel sciences including biology and medicine. It has been widely used in quantitative morphologic studies mainly in calculating the fractal dimension of objects. The fractal dimension describes an objects complexity: it is higher if the object is more complex, that is, its border more rugged, its linear structure more winding, or its space more filled. We use a manual version of Richardsons (ruler-based) method and a most popular computer-based box-counting method applying to the problem of measuring the fractal dimension of dendritic arborization in neurons. We also compare how these methods work with skeletonized vs. unskeletonized binary images. We show that for dendrite arborization, the mean box dimension of unskeletonized images is significantly larger than that of skeletonized images. We also show that the box-counting method is sensitive to an objects orientation, whereas the ruler-based dimension is unaffected by skeletonizing and orientation. We show that the mean fractal dimension measured using the ruler-based method is significantly smaller than that measured using the box-counting method. Whereas the box-counting method requires defined usage that limits its utility for analyzing dendritic arborization, the ruler-based method based on Richardsons model presented here can be used more liberally. Although this method is rather tedious to use manually, an accessible computer-based implementation for the neuroscientist has not yet been made available.