scholarly journals Activation of rat brain ornithine decarboxylase by GTP

1994 ◽  
Vol 300 (2) ◽  
pp. 577-582 ◽  
Author(s):  
P T Kilpeläinen ◽  
O A Hietala

The activity of ornithine decarboxylase (ODC) measured in different regions of rat brain was highest in the hippocampus and lowest in the cerebellum. The ODC activity of a crude extract of the cerebellum was increased by the addition of GTP to the enzyme assay. Following dissociation of the ODC-antizyme complex by Sephadex G-75 chromatography in buffer containing 0.25 M NaCl, the GTP-activatable ODC was found in every brain region analysed. This GTP-activatable brain ODC has greater affinity for antizyme than the non-GTP-activatable brain ODC or the kidney ODC. The irreversible inhibitor of ODC, alpha-difluoromethylornithine (DFMO), inhibited approx. 60% of the ODC activity of all brain regions, whereas kidney ODC was inhibited totally by DFMO. When extracts of brain and kidney were incubated at 55 degrees C, kidney ODC was rapidly inactivated, but brain ODC was more heat-stable. Brain ODC, but not kidney ODC, was activated by GTP and ATP, and also by their deoxy forms. The K1/2 for activation of the enzyme was 2 microM for GTP and 40 microM for ATP. Using partially purified brain ODC, the activation by GTP was irreversible. These results demonstrate for the first time that the GTP-activatable ODC exists in the brain and is associated with the antizyme. The possible mechanisms of activation by GTP, the significance of this finding for the regulation of brain ODC, and the similarities to and differences from the GTP-activatable ODC found in certain rodent and human tumours are all discussed.

1989 ◽  
Vol 121 (2) ◽  
pp. 331-335 ◽  
Author(s):  
M. C. Ruiz de Elvira ◽  
A. K. Sinha ◽  
M. Pickard ◽  
M. Ballabio ◽  
M. Hubank ◽  
...  

ABSTRACT Calmodulin-regulated phosphatase activity was measured in the brain of 2-month-old rats born from hypothyroid and normal dams, using a fluorometric enzyme assay developed for this purpose. Calmodulin content was measured in the same brain regions by radioimmunoassay. Significant differences between groups in weight and protein content, basal phosphatase and calmodulin-regulated phosphatase activity were found. The brain region most affected was the cerebellum, where basal and calmodulin-regulated phosphatase activities, and protein content were increased. The data point towards a lasting effect of maternal hypothyroxinaemia on the brain function of the progeny. Journal of Endocrinology (1989) 121, 331–335


2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Seiki Tajima ◽  
Shigeyuki Yamamoto ◽  
Masaaki Tanaka ◽  
Yosky Kataoka ◽  
Masao Iwase ◽  
...  

Fatigue is an indispensable bioalarm to avoid exhaustive state caused by overwork or stresses. It is necessary to elucidate the neural mechanism of fatigue sensation for managing fatigue properly. We performedH2O  15positron emission tomography scans to indicate neural activations while subjects were performing 35-min fatigue-inducing task trials twice. During the positron emission tomography experiment, subjects performed advanced trail-making tests, touching the target circles in sequence located on the display of a touch-panel screen. In order to identify the brain regions associated with fatigue sensation, correlation analysis was performed using statistical parametric mapping method. The brain region exhibiting a positive correlation in activity with subjective sensation of fatigue, measured immediately after each positron emission tomography scan, was located in medial orbitofrontal cortex (Brodmann's area 10/11). Hence, the medial orbitofrontal cortex is a brain region associated with mental fatigue sensation. Our findings provide a new perspective on the neural basis of fatigue.


Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 3920-3925 ◽  
Author(s):  
Qin Wang ◽  
Fang Du ◽  
Zhong-Ming Qian ◽  
Xiao Hu Ge ◽  
Li Zhu ◽  
...  

Hepcidin plays an essential role in maintaining normal iron homeostasis outside the brain. This recently discovered iron regulation hormone is predominantly expressed in the liver, and regulated by iron and hypoxia. As an antimicrobial peptide, this hormone is also elevated during infections and inflammation. In this study we investigated the expression of hepcidin mRNA and protein in different brain regions, including the cortex, hippocampus, striatum, and substantia nigra, and the effects of lipopolysaccharide (LPS) on the expression of hepcidin using quantitative real-time RT-PCR and immunofluorescence analysis. Our data provided further evidence for the existence of hepcidin in all the regions we examined. We also demonstrated for the first time that LPS administration by iv injection can regulate the expression of hepcidin mRNA and protein not only in peripheral organs such as the liver, but also in the brain. LPS induced a significant increase in the expression of hepcidin mRNA and protein in the cortex and substantia nigra, but not in the hippocampus and striatum, indicating a regionally specific regulation of LPS on hepcidin in the brain. The relevant mechanisms and the functions of hepcidin in the brain remain to be elucidated.


1979 ◽  
Vol 57 (6) ◽  
pp. 595-599 ◽  
Author(s):  
P. D. Hrdina ◽  
K. Elson

The effect of tricyclic antidepressants, chlorpromazine, and some monoamine oxidase inhibitors on the accumulation of [14C]choline by crude synaptosomal (P2) fraction from different regions of rat brain (cortex, striatum, and hippocampus) was investigated. Analysis of choline uptake kinetics resulted in high- and low-affinity components with different Michaelis constants. All tricyclic antidepressants tested inhibited in a dose-dependent manner the high-affinity choline uptake in the three regions, amitriptyline being the most potent. The IC50 values correlated significantly with the relative potencies of imipramine congeners in binding to muscarinic receptors in the brain. Neither tranylcypromine nor pargyline in concentrations up to 0.1 mM had any effect on choline transport. Concentrations of tricyclic antidepressants effective in inhibiting the uptake of choline failed to influence significantly the activity of choline acetyltransferase in brain regions examined. The results suggest that the effect of imipramine congeners on high-affinity choline uptake may be reflected in the anticholinergic properties of these compounds.


1984 ◽  
Vol 218 (1) ◽  
pp. 131-138 ◽  
Author(s):  
S F Leong ◽  
J B Clark

The development of key enzyme activities concerned with glucose metabolism was studied in six regions of the rat brain in animals from just before birth (-2 days) through the neonatal and suckling period until adulthood (60 days old). The brain regions studied were the cerebellum, medulla oblongata and pons, hypothalamus, striatum, mid-brain and cortex. The enzymes whose developmental patterns were investigated were hexokinase (EC 2.7.1.1), aldolase (EC 4.1.2.13), lactate dehydrogenase (EC 1.1.1.27) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49). Hexokinase, aldolase and lactate dehydrogenase activities develop as a single cluster in all the regions studied, although the timing of this development varies from region to region. Glucose-6-phosphate dehydrogenase activity, however, declines relative to glycolytic enzyme activity as the brain matures. When the different brain regions are compared, it is clear that the medulla develops its glycolytic potential, as indicated by its potential enzyme activity, considerably earlier than the other regions (hypothalamus, striatum and mid-brain), with the cortex and cerebellar activities developing even later. This enzyme developmental sequence correlates well with the neurophylogenetic development of the brain and adds support to the hypothesis that the development of the potential for glycolysis in the brain is a necessary prerequisite for the development of neurological competence.


Endocrinology ◽  
2011 ◽  
Vol 152 (1) ◽  
pp. 223-235 ◽  
Author(s):  
Anne T. M. Konkle ◽  
Margaret M. McCarthy

Abstract The prevailing view of sexual differentiation of mammalian brain is that androgen synthesized in the fetal and neonatal testis and aromatized centrally during a perinatal sensitive period is the sole source of brain estradiol and the primary determinant of sex differences. Subregions of the diencephalon are among the most sexually dimorphic in the brain, and there are well-established sex differences in the amount of testosterone and estradiol measured in the hypothalamus and preoptic area during the perinatal period. We previously reported unexpectedly high estradiol in the hippocampus and cortex of both male and female newborn rat. This prompted a thorough investigation of the developmental profile of steroids in the rat brain using RIA to quantify the level of estradiol, testosterone, and dihydrotestosterone in discrete subregions of the brain from embryonic d 19 to adulthood. Plasma estradiol levels from individual animals were assessed when sufficient sample was available. A significant sex difference in hypothalamic testosterone prior to birth was consistent with previous findings. Postnatally, there was a distinct pattern of changing steroid concentrations in each brain region, and these were unrelated to circulating steroid. Removal of the gonads and adrenals at birth did not significantly reduce steroids in any brain region assayed 3 d later. Aromatase activity was detectable in all brain areas at birth, and the difference in activity level paralleled the observed regional differences in estradiol content. Based on these findings, we propose that steroidogenesis in the brain, independent of peripherally derived precursors, may play a critical role in mammalian brain development of both sexes, beyond the establishment of sex differences.


2020 ◽  
Author(s):  
Jianxiao Wu ◽  
Simon B. Eickhoff ◽  
Felix Hoffstaedter ◽  
Kaustubh R. Patil ◽  
Holger Schwender ◽  
...  

AbstractThe recent availability of population-based studies with neuroimaging and behavioral measurements opens promising perspectives to investigate the relationships between interindividual variability in brain regions’ connectivity and behavioral phenotypes. However, the multivariate nature of connectivity-based prediction model severely limits the insight into brain-behavior patterns for neuroscience. To address this issue, we propose a connectivity-based psychometric prediction framework based on individual regions’ connectivity profiles. We first illustrate two main applications: 1) single brain region’s predictive power for a range of psychometric variables 2) single psychometric variable’s predictive power variation across brain region. We compare the patterns of brain-behavior provided by these approaches to the brain-behavior relationships from activation approaches. Then, capitalizing on the increased transparency of our approach, we demonstrate how the influence of various data processing and analyses can directly influence the patterns of brain-behavior relationships. Such region-based prediction approach can hence contribute to neurobiological validity in the study of brain-behavior relationships.


2013 ◽  
Vol 421 ◽  
pp. 528-533
Author(s):  
Hua Chin Lee ◽  
Li Wei Ko ◽  
Kuan Lin Lai ◽  
Hui Ling Huang ◽  
Meng Shue Song ◽  
...  

Prediction of resting-state electroencephalography (EEG) usinghigh-dimensional pattern is a challenge due to the uniqueness of each persons brainwave. This study uses the headache EEG recording as the example, and predicts the informative different states by using an intelligent feature selection method. Vomiting and nausea are usually appeared in headache attacks, andit is sensitive to light, sound, or movement. In this study, we use the EEG recording with four classes (inter-headache, pre-headache, headache and post-headache) as the medical database. This study focuses three merits: First, we establish two balanced datasets which contain 2-class (inter-headache and headache) and 4-class brainwave datasets from the original imbalanced headache database so that there is no bias of the prediction system. The 2-class dataset consists of 22 subjects and 176 trials, and the 4-class dataset consists of 40 subjects and 320 trials. Secondly, we propose an efficient SVM-based method for predicting the headache attacks from the EEGby using an inheritable bi-objective combinatorial genetic algorithm (IBCGA). IBCGA automatically selects important features from the brainwave, and the 2-class prediction accuracy of leave-one-trial-out independenttest is 81.25%. Third, from the analysis of the brain region and channel frequency, the brain region T4 is the most important brain regions and alpha and beta frequencies are the most informative frequencies.


1991 ◽  
Vol 71 (3) ◽  
pp. 1057-1061 ◽  
Author(s):  
J. Zhang ◽  
C. A. Piantadosi

Toxicity to the central nervous system (CNS) by hyperbaric oxygen (HBO) presumably relates to increased production of reactive oxygen species. The sites of generation of reactive oxygen species during HBO, however, have not been fully characterized in the brain. We investigated the relationship between regional generation of hydrogen peroxide (H2O2) in the brain in the presence of an irreversible inhibitor of catalase, aminotriazole (ATZ), and protection from CNS O2 toxicity by a monoamine oxidase (MAO) inhibitor, pargyline. At 6 ATA of oxygen, pargyline significantly protected rats from CNS O2 toxicity whereas ATZ enhanced O2 toxicity. In animals pretreated with ATZ, HBO inactivated 21–40% more catalase than air exposure in the six brain regions studied. Because ATZ-mediated inactivation of catalase was H2O2 dependent, the decrease in catalase activity during hyperoxia was proportional to the intracellular production of H2O2. Pargyline, administered 30 min before HBO, inhibited MAO by greater than 90%, prevented ATZ inhibition of catalase activity during HBO, and reversed the augmentation of CNS O2 toxicity by ATZ. These findings indicate that H2O2 generated by MAO during hyperoxia is important to the pathogenesis of CNS O2 toxicity in rats.


Author(s):  
Wei-Li Kuan ◽  
Katherine Stott ◽  
Xiaoling He ◽  
Tobias C. Wood ◽  
Sujeong Yang ◽  
...  

AbstractParkinson’s disease (PD) is an α-synucleinopathy characterized by the progressive loss of specific neuronal populations. Here, we develop a novel approach to transvascularly deliver proteins of complex quaternary structures, including α-synuclein preformed fibrils (pff). We show that a single systemic administration of α-synuclein pff triggers pathological transformation of endogenous α-synuclein in non-transgenic rats, which leads to neurodegeneration in discrete brain regions. Specifically, pff-exposed animals displayed a progressive deterioration in gastrointestinal and olfactory functions, which corresponded with the presence of cellular pathology in the central and enteric nervous systems. The α-synuclein pathology generated was both time dependent and region specific. Interestingly, the most significant neuropathological changes were observed in those brain regions affected in the early stages of PD. Our data therefore demonstrate for the first time that a single, transvascular administration of α-synuclein pff can lead to selective regional neuropathology resembling the premotor stage of idiopathic PD. Furthermore, this novel delivery approach could also be used to deliver a range of other pathogenic, as well as therapeutic, protein cargos transvascularly to the brain.


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