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Sample records for selective brain steroidogenic

  1. Selective Inhibition of Steroidogenic Enzymes by Ketoconazole in Rat Ovary Cells

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    Michael Gal

    2014-01-01

    Full Text Available Objective Ketoconazole (KCZ is an anti-fungal agent extensively used for clinical applications related to its inhibitory effects on adrenal and testicular steroidogenesis. Much less information is available on the effects of KCZ on synthesis of steroid hormones in the ovary. The present study aimed to characterize the in situ effects of KCZ on steroidogenic enzymes in primary rat ovary cells. Methods Following the induction of folliculogenesis in gonadotropin treated rats, freshly prepared ovarian cells were incubated in suspension for up to four hours while radiolabeled steroid substrates were added and time dependent generation of their metabolic products was analyzed by thin layer chromatography (TLC. Results KCZ inhibits the P450 steroidogenic enzymes in a selective and dose dependent manner, including cholesterol side-chain cleavage cytochrome P450 (CYP11A1/P450scc, the 17α-hydroxylase activity of CYP17A1/P450c17, and CYP19A1/P450arom, with IC 50 values of 0.3, 1.8, and 0.3 μg/mL (0.56, 3.36, and 0.56 μM, respectively. Unaffected by KCZ, at 10 μg/mL, were the 17,20 lyase activity of CYP17A1, as well as five non-cytochrome steroidogenic enzymes including 3β-hydroxysteroid dehydrogenase-δ 5-4 isomerase type 1 (3βHSD1, 5α-reductase, 20α-hydroxysteroid dehydrogenase (20α-HSD, 3α-hydroxysteroid dehydrogenase (3α-HSD, and 17β-hydroxysteroid dehydrogenase type 1 (17HSD1. Conclusion These findings map the effects of KCZ on the ovarian pathways of progestin, androgen, and estrogen synthesis. Hence, the drug may have a potential use as an acute and reversible modulator of ovarian steroidogenesis in pathological circumstances.

  2. Selective vulnerability in brain hypoxia

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    Cervos-Navarro, J.; Diemer, Nils Henrik

    1991-01-01

    Neuropathology, selective vulnerability, brain hypoxia, vascular factors, excitotoxicity, ion homeostasis......Neuropathology, selective vulnerability, brain hypoxia, vascular factors, excitotoxicity, ion homeostasis...

  3. Steroidogenic factor 1 directs programs regulating diet-induced thermogenesis and leptin action in the ventral medial hypothalamic nucleus

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    The transcription factor steroidogenic factor 1 (SF-1) is exclusively expressed in the brain in the ventral medial hypothalamic nucleus (VMH) and is required for the development of this nucleus. However, the physiological importance of transcriptional programs regulated by SF-1 in the VMH is not wel...

  4. Evolution of brain region volumes during artificial selection for relative brain size.

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    Kotrschal, Alexander; Zeng, Hong-Li; van der Bijl, Wouter; Öhman-Mägi, Caroline; Kotrschal, Kurt; Pelckmans, Kristiaan; Kolm, Niclas

    2017-12-01

    The vertebrate brain shows an extremely conserved layout across taxa. Still, the relative sizes of separate brain regions vary markedly between species. One interesting pattern is that larger brains seem associated with increased relative sizes only of certain brain regions, for instance telencephalon and cerebellum. Till now, the evolutionary association between separate brain regions and overall brain size is based on comparative evidence and remains experimentally untested. Here, we test the evolutionary response of brain regions to directional selection on brain size in guppies (Poecilia reticulata) selected for large and small relative brain size. In these animals, artificial selection led to a fast response in relative brain size, while body size remained unchanged. We use microcomputer tomography to investigate how the volumes of 11 main brain regions respond to selection for larger versus smaller brains. We found no differences in relative brain region volumes between large- and small-brained animals and only minor sex-specific variation. Also, selection did not change allometric scaling between brain and brain region sizes. Our results suggest that brain regions respond similarly to strong directional selection on relative brain size, which indicates that brain anatomy variation in contemporary species most likely stem from direct selection on key regions. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  5. Positive selection on gene expression in the human brain

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    Khaitovich, Philipp; Tang, Kun; Franz, Henriette

    2006-01-01

    Recent work has shown that the expression levels of genes transcribed in the brains of humans and chimpanzees have changed less than those of genes transcribed in other tissues [1] . However, when gene expression changes are mapped onto the evolutionary lineage in which they occurred, the brain...... shows more changes than other tissues in the human lineage compared to the chimpanzee lineage [1] , [2] and [3] . There are two possible explanations for this: either positive selection drove more gene expression changes to fixation in the human brain than in the chimpanzee brain, or genes expressed...... in the brain experienced less purifying selection in humans than in chimpanzees, i.e. gene expression in the human brain is functionally less constrained. The first scenario would be supported if genes that changed their expression in the brain in the human lineage showed more selective sweeps than other genes...

  6. Primate brain architecture and selection in relation to sex.

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    Lindenfors, Patrik; Nunn, Charles L; Barton, Robert A

    2007-05-10

    Social and competitive demands often differ between the sexes in mammals. These differing demands should be expected to produce variation in the relative sizes of various brain structures. Sexual selection on males can be predicted to influence brain components handling sensory-motor skills that are important for physical competition or neural pathways involving aggression. Conversely, because female fitness is more closely linked to ecological factors and social interactions that enable better acquisition of resources, social selection on females should select for brain components important for navigating social networks. Sexual and social selection acting on one sex could produce sexual dimorphism in brain structures, which would result in larger species averages for those same brain structures. Alternatively, sex-specific selection pressures could produce correlated effects in the other sex, resulting in larger brain structures for both males and females of a species. Data are presently unavailable for the sex-specific sizes of brain structures for anthropoid primates, but under either scenario, the effects of sexual and social selection should leave a detectable signal in average sizes of brain structures for different species. The degree of male intra-sexual selection was positively correlated with several structures involved in autonomic functions and sensory-motor skills, and in pathways relating to aggression and aggression control. The degree of male intra-sexual selection was not correlated with relative neocortex size, which instead was significantly positively correlated with female social group size, but negatively correlated with male group size. Sexual selection on males and social selection on females have exerted different effects on primate brain architecture. Species with a higher degree of male intra-sexual selection carry a neural signature of an evolutionary history centered on physical conflicts, but no traces of increased demands on

  7. Primate brain architecture and selection in relation to sex

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    Nunn Charles L

    2007-05-01

    Full Text Available Abstract Background Social and competitive demands often differ between the sexes in mammals. These differing demands should be expected to produce variation in the relative sizes of various brain structures. Sexual selection on males can be predicted to influence brain components handling sensory-motor skills that are important for physical competition or neural pathways involving aggression. Conversely, because female fitness is more closely linked to ecological factors and social interactions that enable better acquisition of resources, social selection on females should select for brain components important for navigating social networks. Sexual and social selection acting on one sex could produce sexual dimorphism in brain structures, which would result in larger species averages for those same brain structures. Alternatively, sex-specific selection pressures could produce correlated effects in the other sex, resulting in larger brain structures for both males and females of a species. Data are presently unavailable for the sex-specific sizes of brain structures for anthropoid primates, but under either scenario, the effects of sexual and social selection should leave a detectable signal in average sizes of brain structures for different species. Results The degree of male intra-sexual selection was positively correlated with several structures involved in autonomic functions and sensory-motor skills, and in pathways relating to aggression and aggression control. The degree of male intra-sexual selection was not correlated with relative neocortex size, which instead was significantly positively correlated with female social group size, but negatively correlated with male group size. Conclusion Sexual selection on males and social selection on females have exerted different effects on primate brain architecture. Species with a higher degree of male intra-sexual selection carry a neural signature of an evolutionary history centered on

  8. Steroidogenic alterations and adrenal androgen excess in PCOS.

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    Doi, Suhail A R; Al-Zaid, Mona; Towers, Philip A; Scott, Christopher J; Al-Shoumer, Kamal A S

    2006-09-01

    This cross-sectional study was undertaken to improve our understanding of the steroidogenic alterations leading to adrenal hyperandrogenism in polycystic ovarian syndrome (PCOS). Two-hundred and thirty-four women with clinical and biochemical features suggestive of PCOS underwent metabolic and hormonal evaluation. We used the androstenedione/DHEAS ratio as a surrogate for the level of ovarian 3betaHSD activity. We then selected the 90th percentile for the ratio in those with elevated DHEAS (>9 micromol/l) as the cut-off level beyond which excess DHEAS production will be minimized by excess ovarian 3betaHSD activity. This cut-off level was at a ratio of 1.5 and all PCOS women were then divided into two groups, the higher (>1.5) being the group with excess ovarian 3betaHSD activity. We hypothesized that women with a high ratio would be unlikely to have DHEAS excess due to the rapid conversion of DHEA to androstenedione. Those with a low ratio (concordant ovarian and adrenal steroidogenesis) could then either have high DHEAS or normal DHEAS, depending on whether CYP17 activity was higher or lower respectively. Insulin resistance was found to be associated with decreased CYP17 activity while irregular cycles and neuroendocrine dysfunction were determined to be associated with higher ovarian 3betaHSD activity. Adrenal androgen excess in PCOS seems to be related to insulin sensitivity as well as decreased activity of 3betaHSD, the latter being preferentially present in those women with regular cycles or without neuroendocrine dysfunction.

  9. Selective estrogen receptor modulators as brain therapeutic agents

    OpenAIRE

    Arévalo, María Ángeles; Santos-Galindo, María; Lagunas, Natalia; Azcoitia, I.; García-Segura, Luis M.

    2011-01-01

    Selective estrogen receptor modulators (SERMs), used for the treatment of breast cancer, osteoporosis, and menopausal symptoms, affect the nervous system. Some SERMs trigger neuroprotective mechanisms and reduce neural damage in different experimental models of neural trauma, brain inflammation, neurodegenerative diseases, cognitive impairment, and affective disorders. New SERMs with specific actions on neurons and glial cells may represent promising therapeutic tools for the brain. © 2011 So...

  10. Sexual selection and the evolution of brain size in primates.

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    Schillaci, Michael A

    2006-12-20

    Reproductive competition among males has long been considered a powerful force in the evolution of primates. The evolution of brain size and complexity in the Order Primates has been widely regarded as the hallmark of primate evolutionary history. Despite their importance to our understanding of primate evolution, the relationship between sexual selection and the evolutionary development of brain size is not well studied. The present research examines the evolutionary relationship between brain size and two components of primate sexual selection, sperm competition and male competition for mates. Results indicate that there is not a significant relationship between relative brain size and sperm competition as measured by relative testis size in primates, suggesting sperm competition has not played an important role in the evolution of brain size in the primate order. There is, however, a significant negative evolutionary relationship between relative brain size and the level of male competition for mates. The present study shows that the largest relative brain sizes among primate species are associated with monogamous mating systems, suggesting primate monogamy may require greater social acuity and abilities of deception.

  11. Sexual selection and the evolution of brain size in primates.

    Directory of Open Access Journals (Sweden)

    Michael A Schillaci

    Full Text Available Reproductive competition among males has long been considered a powerful force in the evolution of primates. The evolution of brain size and complexity in the Order Primates has been widely regarded as the hallmark of primate evolutionary history. Despite their importance to our understanding of primate evolution, the relationship between sexual selection and the evolutionary development of brain size is not well studied. The present research examines the evolutionary relationship between brain size and two components of primate sexual selection, sperm competition and male competition for mates. Results indicate that there is not a significant relationship between relative brain size and sperm competition as measured by relative testis size in primates, suggesting sperm competition has not played an important role in the evolution of brain size in the primate order. There is, however, a significant negative evolutionary relationship between relative brain size and the level of male competition for mates. The present study shows that the largest relative brain sizes among primate species are associated with monogamous mating systems, suggesting primate monogamy may require greater social acuity and abilities of deception.

  12. Deprivation selectively modulates brain potentials to food pictures

    OpenAIRE

    Stockburger, Jessica; Weike, Almut I.; Hamm, Alfons O.; Schupp, Harald Thomas

    2008-01-01

    Event-related brain potentials (ERPs) were used to examine whether the processing of food pictures is selectively modulated by changes in the motivational state of the observer. Sixteen healthy male volunteers were tested twice 1 week apart, either after 24 hr of food deprivation or after normal food intake. ERPs were measured while participants viewed appetitive food pictures as well as standard emotional and neutral control pictures. Results show that the ERPs to food pictures in a hungry, ...

  13. Selective neuronal vulnerability to oxidative stress in the brain

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    Xinkun Wang

    2010-03-01

    Full Text Available Oxidative stress (OS, caused by the imbalance between the generation and detoxification of reactive oxygen and nitrogen species (ROS/RNS, plays an important role in brain aging, neurodegenerative diseases, and other related adverse conditions, such as ischemia. While ROS/RNS serve as signaling molecules at physiological levels, an excessive amount of these molecules leads to oxidative modification and, therefore, dysfunction of proteins, nucleic acids, and lipids. The response of neurons to this pervasive stress, however, is not uniform in the brain. While many brain neurons can cope with a rise in OS, there are select populations of neurons in the brain that are vulnerable. Because of their selective vulnerability, these neurons are usually the first to exhibit functional decline and cell death during normal aging, or in age-associated neurodegenerative diseases, such as Alzheimer’s disease. Understanding the molecular and cellular mechanisms of selective neuronal vulnerability (SNV to OS is important in the development of future intervention approaches to protect such vulnerable neurons from the stresses of the aging process and the pathological states that lead to neurodegeneration. In this review, the currently known molecular and cellular factors that contribute to SNV to OS are summarized. Included among the major underlying factors are high intrinsic OS, high demand for ROS/RNS-based signaling, low ATP production, mitochondrial dysfunction, and high inflammatory response in vulnerable neurons. The contribution to the selective vulnerability of neurons to OS by other intrinsic or extrinsic factors, such as deficient DNA damage repair, low calcium-buffering capacity, and glutamate excitotoxicity, are also discussed.

  14. Quantitative analysis of task selection for brain-computer interfaces

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    Llera, Alberto; Gómez, Vicenç; Kappen, Hilbert J.

    2014-10-01

    Objective. To assess quantitatively the impact of task selection in the performance of brain-computer interfaces (BCI). Approach. We consider the task-pairs derived from multi-class BCI imagery movement tasks in three different datasets. We analyze for the first time the benefits of task selection on a large-scale basis (109 users) and evaluate the possibility of transferring task-pair information across days for a given subject. Main results. Selecting the subject-dependent optimal task-pair among three different imagery movement tasks results in approximately 20% potential increase in the number of users that can be expected to control a binary BCI. The improvement is observed with respect to the best task-pair fixed across subjects. The best task-pair selected for each subject individually during a first day of recordings is generally a good task-pair in subsequent days. In general, task learning from the user side has a positive influence in the generalization of the optimal task-pair, but special attention should be given to inexperienced subjects. Significance. These results add significant evidence to existing literature that advocates task selection as a necessary step towards usable BCIs. This contribution motivates further research focused on deriving adaptive methods for task selection on larger sets of mental tasks in practical online scenarios.

  15. Deprivation selectively modulates brain potentials to food pictures.

    Science.gov (United States)

    Stockburger, Jessica; Weike, Almut I; Hamm, Alfons O; Schupp, Harald T

    2008-08-01

    Event-related brain potentials (ERPs) were used to examine whether the processing of food pictures is selectively modulated by changes in the motivational state of the observer. Sixteen healthy male volunteers were tested twice 1 week apart, either after 24 hr of food deprivation or after normal food intake. ERPs were measured while participants viewed appetitive food pictures as well as standard emotional and neutral control pictures. Results show that the ERPs to food pictures in a hungry, rather than satiated, state were associated with enlarged positive potentials over posterior sensor sites in a time window of 170-310 ms poststimulus. Minimum-norm analysis suggests the enhanced processing of food cues primarily in occipito-temporo-parietal regions. In contrast, processing of standard emotional and neutral pictures was not modulated by food deprivation. Considered from the perspective of motivated attention, the selective change of food cue processing may reflect a state-dependent change in stimulus salience.

  16. Selectively altering belief formation in the human brain

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    Sharot, Tali; Kanai, Ryota; Marston, David; Korn, Christoph W.; Rees, Geraint; Dolan, Raymond J.

    2012-01-01

    Humans form beliefs asymmetrically; we tend to discount bad news but embrace good news. This reduced impact of unfavorable information on belief updating may have important societal implications, including the generation of financial market bubbles, ill preparedness in the face of natural disasters, and overly aggressive medical decisions. Here, we selectively improved people’s tendency to incorporate bad news into their beliefs by disrupting the function of the left (but not right) inferior frontal gyrus using transcranial magnetic stimulation, thereby eliminating the engrained “good news/bad news effect.” Our results provide an instance of how selective disruption of regional human brain function paradoxically enhances the ability to incorporate unfavorable information into beliefs of vulnerability. PMID:23011798

  17. Brain activity associated with selective attention, divided attention and distraction.

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    Salo, Emma; Salmela, Viljami; Salmi, Juha; Numminen, Jussi; Alho, Kimmo

    2017-06-01

    Top-down controlled selective or divided attention to sounds and visual objects, as well as bottom-up triggered attention to auditory and visual distractors, has been widely investigated. However, no study has systematically compared brain activations related to all these types of attention. To this end, we used functional magnetic resonance imaging (fMRI) to measure brain activity in participants performing a tone pitch or a foveal grating orientation discrimination task, or both, distracted by novel sounds not sharing frequencies with the tones or by extrafoveal visual textures. To force focusing of attention to tones or gratings, or both, task difficulty was kept constantly high with an adaptive staircase method. A whole brain analysis of variance (ANOVA) revealed fronto-parietal attention networks for both selective auditory and visual attention. A subsequent conjunction analysis indicated partial overlaps of these networks. However, like some previous studies, the present results also suggest segregation of prefrontal areas involved in the control of auditory and visual attention. The ANOVA also suggested, and another conjunction analysis confirmed, an additional activity enhancement in the left middle frontal gyrus related to divided attention supporting the role of this area in top-down integration of dual task performance. Distractors expectedly disrupted task performance. However, contrary to our expectations, activations specifically related to the distractors were found only in the auditory and visual cortices. This suggests gating of the distractors from further processing perhaps due to strictly focused attention in the current demanding discrimination tasks. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The brain's silent messenger: using selective attention to decode human thought for brain-based communication.

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    Naci, Lorina; Cusack, Rhodri; Jia, Vivian Z; Owen, Adrian M

    2013-05-29

    The interpretation of human thought from brain activity, without recourse to speech or action, is one of the most provoking and challenging frontiers of modern neuroscience. In particular, patients who are fully conscious and awake, yet, due to brain damage, are unable to show any behavioral responsivity, expose the limits of the neuromuscular system and the necessity for alternate forms of communication. Although it is well established that selective attention can significantly enhance the neural representation of attended sounds, it remains, thus far, untested as a response modality for brain-based communication. We asked whether its effect could be reliably used to decode answers to binary (yes/no) questions. Fifteen healthy volunteers answered questions (e.g., "Do you have brothers or sisters?") in the fMRI scanner, by selectively attending to the appropriate word ("yes" or "no"). Ninety percent of the answers were decoded correctly based on activity changes within the attention network. The majority of volunteers conveyed their answers with less than 3 min of scanning, suggesting that this technique is suited for communication in a reasonable amount of time. Formal comparison with the current best-established fMRI technique for binary communication revealed improved individual success rates and scanning times required to detect responses. This novel fMRI technique is intuitive, easy to use in untrained participants, and reliably robust within brief scanning times. Possible applications include communication with behaviorally nonresponsive patients.

  19. Artificial selection on relative brain size in the guppy reveals costs and benefits of evolving a larger brain.

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    Kotrschal, Alexander; Rogell, Björn; Bundsen, Andreas; Svensson, Beatrice; Zajitschek, Susanne; Brännström, Ioana; Immler, Simone; Maklakov, Alexei A; Kolm, Niclas

    2013-01-21

    The large variation in brain size that exists in the animal kingdom has been suggested to have evolved through the balance between selective advantages of greater cognitive ability and the prohibitively high energy demands of a larger brain (the "expensive-tissue hypothesis"). Despite over a century of research on the evolution of brain size, empirical support for the trade-off between cognitive ability and energetic costs is based exclusively on correlative evidence, and the theory remains controversial. Here we provide experimental evidence for costs and benefits of increased brain size. We used artificial selection for large and small brain size relative to body size in a live-bearing fish, the guppy (Poecilia reticulata), and found that relative brain size evolved rapidly in response to divergent selection in both sexes. Large-brained females outperformed small-brained females in a numerical learning assay designed to test cognitive ability. Moreover, large-brained lines, especially males, developed smaller guts, as predicted by the expensive-tissue hypothesis, and produced fewer offspring. We propose that the evolution of brain size is mediated by a functional trade-off between increased cognitive ability and reproductive performance and discuss the implications of these findings for vertebrate brain evolution. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Distribution of steroidogenic enzymes involved in androgen synthesis in polycystic ovaries: an immunohistochemical study

    NARCIS (Netherlands)

    Kaaijk, E. M.; Sasano, H.; Suzuki, T.; Beek, J. F.; van der Veen, F.

    2000-01-01

    To find an explanation for the possible working mechanism of laparoscopic ovarian electrocautery for the treatment of anovulation in polycystic ovarian syndrome (PCOS), we evaluated the distribution of steroidogenic enzymes involved in the synthesis of ovarian androgens in surgical pathology

  1. Steroidogenic activity of high molecular weight forms of ACTH

    International Nuclear Information System (INIS)

    Gasson, J.C.

    1979-01-01

    The relative steroidogenic potencies of high molecular weight forms of adrenocorticotropic hormone (ACTH) were investigated using in vitro bioassays. In order to prepare pools of separated pro-ACTH/endorphin, ACTH biosynthetic intermediate and glycosylated ACTH (1-39), the protein present in serum-free tissue culture medium obtained from cultured AtT-20/D-16v mouse pituitary tumor cells was concentrated and fractionated by gel filtration. Based on sodium dodecyl sulfate polyacrylamide gel electrophoresis, over 97% of the immunoactive ACTH in each pool had the appropriate molecular weight. Suspensions of isolated rat and guinea pig adrenal cortical cells were prepared by enzymatic dissociation and mechanical dispersion. Cells were incubated in complete tissue culture medium overnight then used in a 2 hour steroid production assay. Synthetic hACTH(1-39) was used as a bioassay and immunoassay standard. The amounts of pro-ACTH/endorphin, ACTH biosynthetic intermediate and glycosylated ACTH(1-39) bioassayed were estimated by ACTH(17-24) radioimmunoassay. All three high molecular weight forms of ACTH were capable of stimulating the same maximal level of steroidogenesis, by both isolated rat and guinea pig adrenal cells, as hACTH(1-39). Glycosylated ACTH(1-39) was equipotent with hACTH(1-39); pro-ACTH/endorphin and ACTH biosynthetic intermediate were two orders of magnitude less potent than hACTH(1-39) in both bioassay systems

  2. Automated selection of brain regions for real-time fMRI brain-computer interfaces

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    Lührs, Michael; Sorger, Bettina; Goebel, Rainer; Esposito, Fabrizio

    2017-02-01

    Objective. Brain-computer interfaces (BCIs) implemented with real-time functional magnetic resonance imaging (rt-fMRI) use fMRI time-courses from predefined regions of interest (ROIs). To reach best performances, localizer experiments and on-site expert supervision are required for ROI definition. To automate this step, we developed two unsupervised computational techniques based on the general linear model (GLM) and independent component analysis (ICA) of rt-fMRI data, and compared their performances on a communication BCI. Approach. 3 T fMRI data of six volunteers were re-analyzed in simulated real-time. During a localizer run, participants performed three mental tasks following visual cues. During two communication runs, a letter-spelling display guided the subjects to freely encode letters by performing one of the mental tasks with a specific timing. GLM- and ICA-based procedures were used to decode each letter, respectively using compact ROIs and whole-brain distributed spatio-temporal patterns of fMRI activity, automatically defined from subject-specific or group-level maps. Main results. Letter-decoding performances were comparable to supervised methods. In combination with a similarity-based criterion, GLM- and ICA-based approaches successfully decoded more than 80% (average) of the letters. Subject-specific maps yielded optimal performances. Significance. Automated solutions for ROI selection may help accelerating the translation of rt-fMRI BCIs from research to clinical applications.

  3. Potent and Selective BACE-1 Peptide Inhibitors Lower Brain Aβ Levels Mediated by Brain Shuttle Transport

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    Nadine Ruderisch

    2017-10-01

    Full Text Available Therapeutic approaches to fight Alzheimer's disease include anti-Amyloidβ (Aβ antibodies and secretase inhibitors. However, the blood-brain barrier (BBB limits the brain exposure of biologics and the chemical space for small molecules to be BBB permeable. The Brain Shuttle (BS technology is capable of shuttling large molecules into the brain. This allows for new types of therapeutic modalities engineered for optimal efficacy on the molecular target in the brain independent of brain penetrating properties. To this end, we designed BACE1 peptide inhibitors with varying lipid modifications with single-digit picomolar cellular potency. Secondly, we generated active-exosite peptides with structurally confirmed dual binding mode and improved potency. When fused to the BS via sortase coupling, these BACE1 inhibitors significantly reduced brain Aβ levels in mice after intravenous administration. In plasma, both BS and non-BS BACE1 inhibitor peptides induced a significant time- and dose-dependent decrease of Aβ. Our results demonstrate that the BS is essential for BACE1 peptide inhibitors to be efficacious in the brain and active-exosite design of BACE1 peptide inhibitors together with lipid modification may be of therapeutic relevance.

  4. Deep brain stimulation for dystonia: patient selection and outcomes

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    Speelman, J. D.; Contarino, M. F.; Schuurman, P. R.; Tijssen, M. A. J.; de Bie, R. M. A.

    2010-01-01

    In a literature survey, 341 patients with primary and 109 with secondary dystonias treated with deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) were identified. In general, the outcomes for primary dystonias were more favourable compared to the secondary forms. For

  5. Deep brain stimulation for dystonia : Patient selection and outcomes

    NARCIS (Netherlands)

    Speelman, J. D.; Contarino, M. F.; Schuurman, P. R.; Tijssen, M. A. J.; de Bie, R. M. A.

    In a literature survey, 341 patients with primary and 109 with secondary dystonias treated with deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) were identified. In general, the outcomes for primary dystonias were more favourable compared to the secondary forms. For

  6. Radioreceptor assay of opioid peptides in selected canine brain regions

    Energy Technology Data Exchange (ETDEWEB)

    Desiderio, D.M.; Takeshita, H.

    1985-09-01

    A radioreceptor assay using the opioid delta receptor-preferring ligand D-/sup 2/ala, D-/sup 5/leu leucine enkephalin (/sup 3/H-DADL) and the broader-specificity ligand /sup 3/H-etorphine was used to measure five HPLC-purified neuropeptide fractions derived from the peptide-rich fraction of tissue homogenates of nine anatomical regions of the canine brain. The receptoractive peptides studied were methionine enkephalin, alpha-neo-endorphin, dynorphin 1-8, methionine enkephalin-Arg-Phe, and leucine enkephalin. These peptides derive from two larger precursors: proenkephalin A, which contains methionine enkephalin, leucine enkephalin, methionine enkephalin-Arg-Phe; and proenkephalin B, which contains alpha-neo-endorphin and dynorphin 1-8. Receptoractive peptides were measured in the peptide-rich fraction derived from homogenates of canine hypothalamus, pituitary, caudate nucleus, amygdala, hippocampus, mid-brain, thalamus, pons-medulla, and cortex.

  7. Radioreceptor assay of opioid peptides in selected canine brain regions

    International Nuclear Information System (INIS)

    Desiderio, D.M.; Takeshita, H.

    1985-01-01

    A radioreceptor assay using the opioid delta receptor-preferring ligand D- 2 ala, D- 5 leu leucine enkephalin ( 3 H-DADL) and the broader-specificity ligand 3 H-etorphine was used to measure five HPLC-purified neuropeptide fractions derived from the peptide-rich fraction of tissue homogenates of nine anatomical regions of the canine brain. The receptoractive peptides studied were methionine enkephalin, alpha-neo-endorphin, dynorphin 1-8, methionine enkephalin-Arg-Phe, and leucine enkephalin. These peptides derive from two larger precursors: proenkephalin A, which contains methionine enkephalin, leucine enkephalin, methionine enkephalin-Arg-Phe; and proenkephalin B, which contains alpha-neo-endorphin and dynorphin 1-8. Receptoractive peptides were measured in the peptide-rich fraction derived from homogenates of canine hypothalamus, pituitary, caudate nucleus, amygdala, hippocampus, mid-brain, thalamus, pons-medulla, and cortex

  8. The steroidogenic response and corpus luteum expression of the steroidogenic acute regulatory protein after human chorionic gonadotropin administration at different times in the human luteal phase.

    Science.gov (United States)

    Kohen, Paulina; Castro, Olga; Palomino, Alberto; Muñoz, Alex; Christenson, Lane K; Sierralta, Walter; Carvallo, Pilar; Strauss, Jerome F; Devoto, Luigi

    2003-07-01

    This study was designed 1) to assess corpus luteum (CL) steroidogenesis in response to exogenous human chorionic gonadotropin (hCG) at different times during the luteal phase, 2) to examine the effect of hCG on steroidogenic acute regulatory protein (StAR) expression within the CL, 3) to correlate StAR expression and luteal steroidogenic responses to hCG, and 4) to determine whether endogenous LH regulates ovarian steroidogenesis in the early luteal phase. Blood was collected before and after hCG treatment for steroid and hCGbeta determinations. CL were obtained at the time of surgery to assess StAR gene and protein expression. During the early luteal phase various women received the GnRH antagonist for 24-48 h; some of them also received hCG 24 h after the GnRH antagonist. A slight steroidogenic response to hCG was observed in early luteal phase; 17alpha-hydroxyprogesterone, but not progesterone (P4), levels were significantly increased 8 h post-hCG, indicating a differential response by the granulosa and theca-lutein cells. The 1.6- and 4.4-kb StAR transcripts and the 37-kDa preprotein and 30-kDa mature StAR protein did not change post-hCG administration in early luteal phase CL. In contrast, the StAR 4.4- and 1.6-kb transcripts diminished significantly (P < 0.05) after the antagonist treatment. Immunohistochemical staining for StAR protein was weak, particularly in granulosa-lutein cells. Treatment with hCG restored StAR mRNA and protein and plasma P4 levels within 24 h in antagonist-treated women. hCG stimulated the highest plasma concentrations of P4 and estradiol in the midluteal phase, indicating its greatest steroidogenic capacity. Midluteal tissue StAR gene and protein expression increased by 1.6- and 1.4-fold after 24 h of hCG treatment, respectively. Administration of hCG resulted in the greatest increment in plasma P4 (4-fold) and 17alpha-hydroxyprogesterone (3-fold) levels over baseline in the late luteal phase. This was associated with an increase in

  9. Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers.

    Science.gov (United States)

    Hirvonen, J; Goodwin, R S; Li, C-T; Terry, G E; Zoghbi, S S; Morse, C; Pike, V W; Volkow, N D; Huestis, M A; Innis, R B

    2012-06-01

    Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB(1) (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB(1) receptors in human subjects who chronically smoke cannabis. Downregulation correlated with years of cannabis smoking and was selective to cortical brain regions. After ∼4 weeks of continuously monitored abstinence from cannabis on a secure research unit, CB(1) receptor density returned to normal levels. This is the first direct demonstration of cortical cannabinoid CB(1) receptor downregulation as a neuroadaptation that may promote cannabis dependence in human brain.

  10. Male and female brain evolution is subject to contrasting selection pressures in primates

    Directory of Open Access Journals (Sweden)

    Dunbar Robin IM

    2007-05-01

    Full Text Available Abstract The claim that differences in brain size across primate species has mainly been driven by the demands of sociality (the "social brain" hypothesis is now widely accepted. Some of the evidence to support this comes from the fact that species that live in large social groups have larger brains, and in particular larger neocortices. Lindenfors and colleagues (BMC Biology 5:20 add significantly to our appreciation of this process by showing that there are striking differences between the two sexes in the social mechanisms and brain units involved. Female sociality (which is more affiliative is related most closely to neocortex volume, but male sociality (which is more competitive and combative is more closely related to subcortical units (notably those associated with emotional responses. Thus different brain units have responded to different selection pressures.

  11. Endogenous Sensory Discrimination and Selection by a Fast Brain Switch for a High Transfer Rate Brain-Computer Interface.

    Science.gov (United States)

    Xu, Ren; Jiang, Ning; Dosen, Strahinja; Lin, Chuang; Mrachacz-Kersting, Natalie; Dremstrup, Kim; Farina, Dario

    2016-08-01

    In this study, we present a novel multi-class brain-computer interface (BCI) for communication and control. In this system, the information processing is shared by the algorithm (computer) and the user (human). Specifically, an electro-tactile cycle was presented to the user, providing the choice (class) by delivering timely sensory input. The user discriminated these choices by his/her endogenous sensory ability and selected the desired choice with an intuitive motor task. This selection was detected by a fast brain switch based on real-time detection of movement-related cortical potentials from scalp EEG. We demonstrated the feasibility of such a system with a four-class BCI, yielding a true positive rate of  ∼ 80% and  ∼ 70%, and an information transfer rate of  ∼ 7 bits/min and  ∼ 5 bits/min, for the movement and imagination selection command, respectively. Furthermore, when the system was extended to eight classes, the throughput of the system was improved, demonstrating the capability of accommodating a large number of classes. Combining the endogenous sensory discrimination with the fast brain switch, the proposed system could be an effective, multi-class, gaze-independent BCI system for communication and control applications.

  12. Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers

    OpenAIRE

    Hirvonen, J; Goodwin, RS; Li, C-T; Terry, GE; Zoghbi, SS; Morse, C; Pike, VW; Volkow, ND; Huestis, MA; Innis, RB

    2011-01-01

    Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB1 (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in human subjects who chronically smoke ca...

  13. Selective Attention to Emotion in the Aging Brain

    Science.gov (United States)

    Samanez-Larkin, Gregory R.; Robertson, Elaine R.; Mikels, Joseph A.; Carstensen, Laura L.; Gotlib, Ian H.

    2009-01-01

    A growing body of research suggests that the ability to regulate emotion remains stable or improves across the adult life span. Socioemotional selectivity theory maintains that this pattern of findings reflects the prioritization of emotional goals. Given that goal-directed behavior requires attentional control, the present study was designed to investigate age differences in selective attention to emotional lexical stimuli under conditions of emotional interference. Both neural and behavioral measures were obtained during an experiment in which participants completed a flanker task that required them to make categorical judgments about emotional and non-emotional stimuli. Older adults showed interference in both the behavioral and neural measures on control trials, but not on emotion trials. Although older adults typically show relatively high levels of interference and reduced cognitive control during non-emotional tasks, they appear to be able successfully to reduce interference during emotional tasks. PMID:19739908

  14. Central nervous system-specific knockout of steroidogenic factor 1 results in increased anxiety-like behavior.

    Science.gov (United States)

    Zhao, Liping; Kim, Ki Woo; Ikeda, Yayoi; Anderson, Kimberly K; Beck, Laurel; Chase, Stephanie; Tobet, Stuart A; Parker, Keith L

    2008-06-01

    Steroidogenic factor 1 (SF-1) plays key roles in adrenal and gonadal development, expression of pituitary gonadotropins, and development of the ventromedial hypothalamic nucleus (VMH). If kept alive by adrenal transplants, global knockout (KO) mice lacking SF-1 exhibit delayed-onset obesity and decreased locomotor activity. To define specific roles of SF-1 in the VMH, we used the Cre-loxP system to inactivate SF-1 in a central nervous system (CNS)-specific manner. These mice largely recapitulated the VMH structural defect seen in mice lacking SF-1 in all tissues. In multiple behavioral tests, mice with CNS-specific KO of SF-1 had significantly more anxiety-like behavior than wild-type littermates. The CNS-specific SF-1 KO mice had diminished expression or altered distribution in the mediobasal hypothalamus of several genes whose expression has been linked to stress and anxiety-like behavior, including brain-derived neurotrophic factor, the type 2 receptor for CRH (Crhr2), and Ucn 3. Moreover, transfection and EMSAs support a direct role of SF-1 in Crhr2 regulation. These findings reveal important roles of SF-1 in the hypothalamic expression of key regulators of anxiety-like behavior, providing a plausible molecular basis for the behavioral effect of CNS-specific KO of this nuclear receptor.

  15. Cationization increases brain distribution of an amyloid-beta protofibril selective F(ab')2 fragment

    OpenAIRE

    Syvänen, Stina; Edén, Desireé; Sehlin, Dag

    2017-01-01

    Antibodies and fragments thereof are, because of high selectivity for their targets, considered as potential therapeutics and biomarkers for several neurological disorders. However, due to their large molecular size, antibodies/fragments do not easily penetrate into the brain. The aim of the present study was to improve the brain distribution via adsorptive-mediated transcytosis of an amyloid-beta (A beta) protofibril selective F(ab')2 fragment (F(ab')2-h158). F(ab')2-h158 was cationized to d...

  16. Gender differences in functional connectivities between insular subdivisions and selective pain-related brain structures.

    Science.gov (United States)

    Dai, Yu-Jie; Zhang, Xin; Yang, Yang; Nan, Hai-Yan; Yu, Ying; Sun, Qian; Yan, Lin-Feng; Hu, Bo; Zhang, Jin; Qiu, Zi-Yu; Gao, Yi; Cui, Guang-Bin; Chen, Bi-Liang; Wang, Wen

    2018-03-14

    The incidence of pain disorders in women is higher than in men, making gender differences in pain a research focus. The human insular cortex is an important brain hub structure for pain processing and is divided into several subdivisions, serving different functions in pain perception. Here we aimed to examine the gender differences of the functional connectivities (FCs) between the twelve insular subdivisions and selected pain-related brain structures in healthy adults. Twenty-six healthy males and 11 age-matched healthy females were recruited in this cross-sectional study. FCs between the 12 insular subdivisions (as 12 regions of interest (ROIs)) and the whole brain (ROI-whole brain level) or 64 selected pain-related brain regions (64 ROIs, ROI-ROI level) were measured between the males and females. Significant gender differences in the FCs of the insular subdivisions were revealed: (1) The FCs between the dorsal dysgranular insula (dId) and other brain regions were significantly increased in males using two different techniques (ROI-whole brain and ROI-ROI analyses); (2) Based on the ROI-whole brain analysis, the FC increases in 4 FC-pairs were observed in males, including the left dId - the right median cingulate and paracingulate/ right posterior cingulate gyrus/ right precuneus, the left dId - the right median cingulate and paracingulate, the left dId - the left angular as well as the left dId - the left middle frontal gyrus; (3) According to the ROI-ROI analysis, increased FC between the left dId and the right rostral anterior cingulate cortex was investigated in males. In summary, the gender differences in the FCs of the insular subdivisions with pain-related brain regions were revealed in the current study, offering neuroimaging evidence for gender differences in pain processing. ClinicalTrials.gov, NCT02820974 . Registered 28 June 2016.

  17. StAR protein and steroidogenic enzyme expressions in the rat Harderian gland.

    Science.gov (United States)

    Falvo, Sara; Chieffi Baccaria, Gabriella; Spaziano, Giuseppe; Rosati, Luigi; Venditti, Massimo; Di Fiore, Maria Maddalena; Santillo, Alessandra

    2018-03-01

    The Harderian gland (HG) of the rat (Rattus norvegicus) secretes copious amounts of lipids, such as cholesterol. Here we report a study of the expressions of the StAR protein and key steroidogenic enzymes in the HG of male and female rats. The objective of the present investigation was to ascertain (a) whether the rat HG is involved in steroid production starting with cholesterol, and (b) whether the pattern of gene and protein expressions together with the enzymatic activities display sexual dimorphism. The results demonstrate, for the first time, the expression of StAR gene and protein, and Cyp11a1, Hsd3b1, Hsd17b3, Srd5a1, Srd5a2 and Cyp19a1 genes in the rat HG. StAR mRNA and protein expressions were much greater in males than in females. Immunohistochemical analysis demonstrated a non-homogeneous StAR distribution among glandular cells. Hsd17b3 and Cyp19a1 mRNA levels were higher in males than in females, whereas Srd5a1 mRNA levels were higher in females than in males. No significant differences were observed in mRNA levels of Cyp11a1, Hsd3b1 and Srd5a2 between sexes. Furthermore, the in vitro experiments demonstrated a higher 5α-reductase activity in the female as compared to the male HG vice versa a higher P450 aro activity in males as compared to females. These results suggest that the Harderian gland can be classified as a steroidogenic tissue because it synthesizes cholesterol, expresses StAR and steroidogenic enzymes involved in both androgen and estrogen synthesis. The dimorphic expression and activity of the steroidogenic enzymes may suggest sex-specific hormonal effects into the HG physiology. Copyright © 2018 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

  18. The Contribution of Serine 194 Phosphorylation to Steroidogenic Acute Regulatory Protein Function

    OpenAIRE

    Sasaki, Goro; Zubair, Mohamad; Ishii, Tomohiro; Mitsui, Toshikatsu; Hasegawa, Tomonobu; Auchus, Richard J.

    2014-01-01

    The steroidogenic acute regulatory protein (StAR) facilitates the delivery of cholesterol to the inner mitochondrial membrane, where the cholesterol side-chain cleavage enzyme catalyzes the initial step of steroid hormone biosynthesis. StAR was initially identified in adrenocortical cells as a phosphoprotein, the expression and phosphorylation of which were stimulated by corticotropin. A number of in vitro studies have implicated cAMP-dependent phosphorylation at serine 194 (S194, S195 in hum...

  19. Ultrastructural and biochemical evidence for the presence of mature steroidogenic acute regulatory protein (StAR) in the cytoplasm of human luteal cells.

    Science.gov (United States)

    Sierralta, Walter D; Kohen, Paulina; Castro, Olga; Muñoz, Alex; Strauss, Jerome F; Devoto, Luigi

    2005-10-20

    The distribution of the steroidogenic acute regulatory protein (StAR) inside thecal and granulosa-lutein cells of human corpus luteum (CL) was assessed by immunoelectron microscopy. We found greater levels of StAR immunolabeling in steroidogenic cells from early- and mid-than in late luteal phase CL and lower levels in cells from women treated with a GnRH antagonist in the mid-luteal phase. Immunoelectron microscopy revealed significant levels of StAR antigen in the mitochondria and in the cytoplasm of luteal cells. The 30 kDa mature StAR protein was present in both mitochondria and cytosol (post-mitochondrial) fractions from homogenates of CL at different ages, whereas cytochrome c and mitochondrial HSP70 were detected only in the mitochondrial fraction. Therefore, we hypothesized that either appreciable processing of StAR 37 kDa pre-protein occurs outside the mitochondria, or mature StAR protein is selectively released into the cytoplasm after mitochondrial processing. The presence of mature StAR in the cytoplasm is consonant with the notion that StAR acts on the outer mitochondrial membrane to effect sterol import, and that StAR may interact with other cytoplasmic proteins involved in cholesterol metabolism, including hormone sensitive lipase.

  20. A New Method of Selective, Rapid Cooling of the Brain: An Experimental Study

    International Nuclear Information System (INIS)

    Allers, Mats; Boris-Moeller, Fredrik; Lunderquist, Anders; Wieloch, Tadeusz

    2006-01-01

    Purpose. To determine whether retrograde perfusion of cooled blood into one internal jugular vein (IJV) in the pig can selectively reduce the brain temperature without affecting the core body temperature (CBT). Methods. In 7 domestic pigs, the left IJV was catheterized on one side and a catheter placed with the tip immediately below the rete mirabile. Thermistors were placed in both brain hemispheres and the brain temperature continuously registered. Thermistors placed in the rectum registered the CBT. From a catheter in the right femoral vein blood was aspirated with the aid of a roller pump, passed through a cooling device, and infused into the catheter in the left IJV at an initial rate of 200 ml/min. Results. Immediately after the start of the infusion of cooled blood (13.8 deg. C) into the IJV, the right brain temperature started to drop from its initial 37.9 deg. C and reached 32 deg. C within 5 min. By increasing the temperature of the perfusate a further drop in the brain temperature was avoided and the brain temperature could be kept around 32 deg. C during the experiment. In 4 of the animals a heating blanket was sufficient to compensate for the slight drop in CBT during the cooling period. Conclusions. We conclude that brain temperature can be reduced in the pig by retrograde perfusion of the internal jugular vein with cooled blood and that the core body temperature can be maintained with the aid of a heating blanket

  1. Selection of optimal treatment scheme for brain metastases of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Dong Mingxin; Zhao Tong; Huang Jingzi; Yu Shukun; Ma Yan; Tian Zhongcheng; Jin Xiangshun; Quan Jizhong; Liu Jin; Wang Dongxu

    2006-01-01

    Objective: To select the optimal treatment scheme for brain metastases of non-small cell lung cancers (NSCLCs). Methods: Seventy-two NSCLC cases diagnosesd by pathology with brain metastases were randomly classified into three groups, Group I, 24 cases with whole brain conventional external fractioned irradiation of D T 36-41 Gy/4-5 w, Group II, 22 eases with y-knife treatment plus whole brain conventional external fractioned irradiation, and Group III, 26 cases with γ-knife plus whole brain conventional external fractioned irradiation in combination with chemotherapy of Vm-26. The surrounding area of tumor was strictly covered with 50% para-central-dosal curve in γ-knife treatment (D T 16-25 Gy with a mean of 16 Gy). The muirleaf collimator was selected according to the volume of tumors. Chemotherapy of Vm-26 (60 mg/m 2 d1-3) was applied during the treatment with whole brain conventional external fractioned irradiation (D T 19-29 Gy/2-3 w), 21 days in a period, 2 periods in total. Results: The median survival time was estimated to be 6.0 months (ranged from 1.2 to 19.0 months) in the Group I, 9.2 months (4.4-30 months) in the Group II, and 10.8 months (5.2-42.2 months) in the Group III. The 1-year and 2-year survival rates were 34.6% and 12.6% , 62.2% and 30.2%, and 70.8% and 35.6% respectively in Group I, Group II, and Group III, respectively. Conclusion: For brain metastases of NSCLC, γ-knife plus whole brain conventional external fractioned irradiation combined with treatment of Vm-26 had a significantly beneficial influence on improvement of the local control and 1-year and 2-year survival. There was no complaint about the side-effects of the treatment. (authors)

  2. Brain activity during divided and selective attention to auditory and visual sentence comprehension tasks

    OpenAIRE

    Moisala, Mona; Salmela, Viljami; Salo, Emma; Carlson, Synnove; Vuontela, Virve; Salonen, Oili; Alho, Kimmo

    2015-01-01

    Using functional magnetic resonance imaging (fMRI), we measured brain activity of human participants while they performed a sentence congruence judgment task in either the visual or auditory modality separately, or in both modalities simultaneously. Significant performance decrements were observed when attention was divided between the two modalities compared with when one modality was selectively attended. Compared with selective attention (i.e., single tasking), divided attention (i.e., dua...

  3. Quantitative Magnetization Transfer Imaging in Human Brain at 3 T via Selective Inversion Recovery

    OpenAIRE

    Dortch, Richard D.; Li, Ke; Gochberg, Daniel F.; Welch, E. Brian; Dula, Adrienne N.; Tamhane, Ashish A.; Gore, John C.; Smith, Seth A.

    2011-01-01

    Quantitative magnetization transfer imaging yields indices describing the interactions between free water protons and immobile, macromolecular protons—including the macromolecular to free pool size ratio (PSR) and the rate of magnetization transfer between pools kmf. This study describes the first implementation of the selective inversion recovery quantitative magnetization transfer method on a clinical 3.0-T scanner in human brain in vivo. Selective inversion recovery data were acquired at 1...

  4. Acoustic Noise Alters Selective Attention Processes as Indicated by Direct Current (DC) Brain Potential Changes

    OpenAIRE

    Trimmel, Karin; Schätzer, Julia; Trimmel, Michael

    2014-01-01

    Acoustic environmental noise, even of low to moderate intensity, is known to adversely affect information processing in animals and humans via attention mechanisms. In particular, facilitation and inhibition of information processing are basic functions of selective attention. Such mechanisms can be investigated by analyzing brain potentials under conditions of externally directed attention (intake of environmental information) versus internally directed attention (rejection of environmental ...

  5. Selective vulnerability related to aging in large-scale resting brain networks.

    Science.gov (United States)

    Zhang, Hong-Ying; Chen, Wen-Xin; Jiao, Yun; Xu, Yao; Zhang, Xiang-Rong; Wu, Jing-Tao

    2014-01-01

    Normal aging is associated with cognitive decline. Evidence indicates that large-scale brain networks are affected by aging; however, it has not been established whether aging has equivalent effects on specific large-scale networks. In the present study, 40 healthy subjects including 22 older (aged 60-80 years) and 18 younger (aged 22-33 years) adults underwent resting-state functional MRI scanning. Four canonical resting-state networks, including the default mode network (DMN), executive control network (ECN), dorsal attention network (DAN) and salience network, were extracted, and the functional connectivities in these canonical networks were compared between the younger and older groups. We found distinct, disruptive alterations present in the large-scale aging-related resting brain networks: the ECN was affected the most, followed by the DAN. However, the DMN and salience networks showed limited functional connectivity disruption. The visual network served as a control and was similarly preserved in both groups. Our findings suggest that the aged brain is characterized by selective vulnerability in large-scale brain networks. These results could help improve our understanding of the mechanism of degeneration in the aging brain. Additional work is warranted to determine whether selective alterations in the intrinsic networks are related to impairments in behavioral performance.

  6. Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury

    Science.gov (United States)

    Xie, Cuicui; Ginet, Vanessa; Sun, Yanyan; Koike, Masato; Zhou, Kai; Li, Tao; Li, Hongfu; Li, Qian; Wang, Xiaoyang; Uchiyama, Yasuo; Truttmann, Anita C.; Kroemer, Guido; Puyal, Julien; Blomgren, Klas; Zhu, Changlian

    2016-01-01

    ABSTRACT Perinatal asphyxia induces neuronal cell death and brain injury, and is often associated with irreversible neurological deficits in children. There is an urgent need to elucidate the neuronal death mechanisms occurring after neonatal hypoxia-ischemia (HI). We here investigated the selective neuronal deletion of the Atg7 (autophagy related 7) gene on neuronal cell death and brain injury in a mouse model of severe neonatal hypoxia-ischemia. Neuronal deletion of Atg7 prevented HI-induced autophagy, resulted in 42% decrease of tissue loss compared to wild-type mice after the insult, and reduced cell death in multiple brain regions, including apoptosis, as shown by decreased caspase-dependent and -independent cell death. Moreover, we investigated the lentiform nucleus of human newborns who died after severe perinatal asphyxia and found increased neuronal autophagy after severe hypoxic-ischemic encephalopathy compared to control uninjured brains, as indicated by the numbers of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3)-, LAMP1 (lysosomal-associated membrane protein 1)-, and CTSD (cathepsin D)-positive cells. These findings reveal that selective neuronal deletion of Atg7 is strongly protective against neuronal death and overall brain injury occurring after HI and suggest that inhibition of HI-enhanced autophagy should be considered as a potential therapeutic target for the treatment of human newborns developing severe hypoxic-ischemic encephalopathy. PMID:26727396

  7. Recent adaptive events in human brain revealed by meta-analysis of positively selected genes.

    Directory of Open Access Journals (Sweden)

    Yue Huang

    Full Text Available BACKGROUND AND OBJECTIVES: Analysis of positively-selected genes can help us understand how human evolved, especially the evolution of highly developed cognitive functions. However, previous works have reached conflicting conclusions regarding whether human neuronal genes are over-represented among genes under positive selection. METHODS AND RESULTS: We divided positively-selected genes into four groups according to the identification approaches, compiling a comprehensive list from 27 previous studies. We showed that genes that are highly expressed in the central nervous system are enriched in recent positive selection events in human history identified by intra-species genomic scan, especially in brain regions related to cognitive functions. This pattern holds when different datasets, parameters and analysis pipelines were used. Functional category enrichment analysis supported these findings, showing that synapse-related functions are enriched in genes under recent positive selection. In contrast, immune-related functions, for instance, are enriched in genes under ancient positive selection revealed by inter-species coding region comparison. We further demonstrated that most of these patterns still hold even after controlling for genomic characteristics that might bias genome-wide identification of positively-selected genes including gene length, gene density, GC composition, and intensity of negative selection. CONCLUSION: Our rigorous analysis resolved previous conflicting conclusions and revealed recent adaptation of human brain functions.

  8. Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress

    Institute of Scientific and Technical Information of China (English)

    De-guo Jiang; Shi-li Jin; Gong-ying Li; Qing-qing Li; Zhi-ruo Li; Hong-xia Ma; Chuan-jun Zhuo; Rong-huan Jiang; Min-jie Ye

    2016-01-01

    Previous studies suggest that serotonin (5-HT) might interact with brain-derived neurotrophic factor (BDNF) during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry andin situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no signiifcant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our ifndings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress.

  9. Selective localization of IgG from cerebrospinal fluid to brain parenchyma

    DEFF Research Database (Denmark)

    Mørch, Marlene Thorsen; Forsberg Sørensen, Sofie; Khorooshi, Reza M. H.

    2018-01-01

    the cerebrospinal fluid and induce subpial and periventricular NMO-like lesions and blood-brain barrier breakdown, in a complement-dependent manner. To investigate how IgG trafficking from cerebrospinal fluid to brain parenchyma can be influenced by injury. IgG from healthy donors was intrathecally injected...... into the cerebrospinal fluid via cisterna magna at 1, 2, 4, or 7 days after a distal stereotactic sterile needle insertion to the striatum. Antibody deposition, detected by staining for human IgG, peaked 1 day after the intrathecal injection and was selectively seen close to the needle insertion. When NMO...

  10. A Wearable Channel Selection-Based Brain-Computer Interface for Motor Imagery Detection.

    Science.gov (United States)

    Lo, Chi-Chun; Chien, Tsung-Yi; Chen, Yu-Chun; Tsai, Shang-Ho; Fang, Wai-Chi; Lin, Bor-Shyh

    2016-02-06

    Motor imagery-based brain-computer interface (BCI) is a communication interface between an external machine and the brain. Many kinds of spatial filters are used in BCIs to enhance the electroencephalography (EEG) features related to motor imagery. The approach of channel selection, developed to reserve meaningful EEG channels, is also an important technique for the development of BCIs. However, current BCI systems require a conventional EEG machine and EEG electrodes with conductive gel to acquire multi-channel EEG signals and then transmit these EEG signals to the back-end computer to perform the approach of channel selection. This reduces the convenience of use in daily life and increases the limitations of BCI applications. In order to improve the above issues, a novel wearable channel selection-based brain-computer interface is proposed. Here, retractable comb-shaped active dry electrodes are designed to measure the EEG signals on a hairy site, without conductive gel. By the design of analog CAR spatial filters and the firmware of EEG acquisition module, the function of spatial filters could be performed without any calculation, and channel selection could be performed in the front-end device to improve the practicability of detecting motor imagery in the wearable EEG device directly or in commercial mobile phones or tablets, which may have relatively low system specifications. Finally, the performance of the proposed BCI is investigated, and the experimental results show that the proposed system is a good wearable BCI system prototype.

  11. Selective Heart, Brain and Body Perfusion in Open Aortic Arch Replacement.

    Science.gov (United States)

    Maier, Sven; Kari, Fabian; Rylski, Bartosz; Siepe, Matthias; Benk, Christoph; Beyersdorf, Friedhelm

    2016-09-01

    Open aortic arch replacement is a complex and challenging procedure, especially in post dissection aneurysms and in redo procedures after previous surgery of the ascending aorta or aortic root. We report our experience with the simultaneous selective perfusion of heart, brain, and remaining body to ensure optimal perfusion and to minimize perfusion-related risks during these procedures. We used a specially configured heart-lung machine with a centrifugal pump as arterial pump and an additional roller pump for the selective cerebral perfusion. Initial arterial cannulation is achieved via femoral artery or right axillary artery. After lower body circulatory arrest and selective antegrade cerebral perfusion for the distal arch anastomosis, we started selective lower body perfusion simultaneously to the selective antegrade cerebral perfusion and heart perfusion. Eighteen patients were successfully treated with this perfusion strategy from October 2012 to November 2015. No complications related to the heart-lung machine and the cannulation occurred during the procedures. Mean cardiopulmonary bypass time was 239 ± 33 minutes, the simultaneous selective perfusion of brain, heart, and remaining body lasted 55 ± 23 minutes. One patient suffered temporary neurological deficit that resolved completely during intensive care unit stay. No patient experienced a permanent neurological deficit or end-organ dysfunction. These high-risk procedures require a concept with a special setup of the heart-lung machine. Our perfusion strategy for aortic arch replacement ensures a selective perfusion of heart, brain, and lower body during this complex procedure and we observed excellent outcomes in this small series. This perfusion strategy is also applicable for redo procedures.

  12. Goal selection versus process control in a brain-computer interface based on sensorimotor rhythms.

    Science.gov (United States)

    Royer, Audrey S; He, Bin

    2009-02-01

    In a brain-computer interface (BCI) utilizing a process control strategy, the signal from the cortex is used to control the fine motor details normally handled by other parts of the brain. In a BCI utilizing a goal selection strategy, the signal from the cortex is used to determine the overall end goal of the user, and the BCI controls the fine motor details. A BCI based on goal selection may be an easier and more natural system than one based on process control. Although goal selection in theory may surpass process control, the two have never been directly compared, as we are reporting here. Eight young healthy human subjects participated in the present study, three trained and five naïve in BCI usage. Scalp-recorded electroencephalograms (EEG) were used to control a computer cursor during five different paradigms. The paradigms were similar in their underlying signal processing and used the same control signal. However, three were based on goal selection, and two on process control. For both the trained and naïve populations, goal selection had more hits per run, was faster, more accurate (for seven out of eight subjects) and had a higher information transfer rate than process control. Goal selection outperformed process control in every measure studied in the present investigation.

  13. Unsupervised categorization with individuals diagnosed as having moderate traumatic brain injury: Over-selective responding.

    Science.gov (United States)

    Edwards, Darren J; Wood, Rodger

    2016-01-01

    This study explored over-selectivity (executive dysfunction) using a standard unsupervised categorization task. Over-selectivity has been demonstrated using supervised categorization procedures (where training is given); however, little has been done in the way of unsupervised categorization (without training). A standard unsupervised categorization task was used to assess levels of over-selectivity in a traumatic brain injury (TBI) population. Individuals with TBI were selected from the Tertiary Traumatic Brain Injury Clinic at Swansea University and were asked to categorize two-dimensional items (pictures on cards), into groups that they felt were most intuitive, and without any learning (feedback from experimenter). This was compared against categories made by a control group for the same task. The findings of this study demonstrate that individuals with TBI had deficits for both easy and difficult categorization sets, as indicated by a larger amount of one-dimensional sorting compared to control participants. Deficits were significantly greater for the easy condition. The implications of these findings are discussed in the context of over-selectivity, and the processes that underlie this deficit. Also, the implications for using this procedure as a screening measure for over-selectivity in TBI are discussed.

  14. Selective binding of 2-[125I]iodo-nisoxetine to norepinephrine transporters in the brain

    International Nuclear Information System (INIS)

    Kung, M.-P.; Choi, Seok-Rye; Hou, Catherine; Zhuang, Z.-P.; Foulon, Catherine; Kung, Hank F.

    2004-01-01

    A radioiodinated ligand, (R)-N-methyl-(2-[ 125 I]iodo-phenoxy)-3-phenylpropylamine, [ 125 I]2-INXT, targeting norepinephrine transporters (NET), was successfully prepared. A no-carrier-added product, [ 125 I]2-INXT, displayed a saturable binding with a high affinity (K d =0.06 nM) in the homogenates prepared from rat cortical tissues as well as from LLC-PK 1 cells expressing NET. A relatively low number of binding sties (B max =55 fmol/mg protein) measured with [ 125 I]2-INXT in rat cortical homogenates is consistent with the value reported for a known NET ligand, [ 3 H]nisoxetine. Competition studies with various compounds on [ 125 I]2-INXT binding clearly confirmed the pharmacological specificity and selectivity for NET binding sites. Following a tail-vein injection of [ 125 I]2-INXT in rats, a good initial brain uptake was observed (0.56% dose at 2 min) followed by a slow washout from the brain (0.2% remained at 3 hours post-injection). The hypothalamus (a NET-rich region) to striatum (a region devoid of NET) ratio was 1.5 at 3 hours post-i.v. injection. Pretreatment of rats with nisoxetine significantly inhibited the uptake of [ 125 I]2-INXT (70-100% inhibition) in locus coeruleus, hypothalamus and raphe nuclei, regions known to have a high density of NET; whereas escitalopram, a serotonin transporter ligand, did not show a similar effect. Ex vivo autoradiography of rat brain sections of [ 125 I]2-INXT (at 3 hours after an i.v. injection) displayed an excellent regional brain localization pattern corroborated to the specific NET distribution in the brain. The specific brain localization was significantly reduced by a dose of nisoxetine pretreatment. Taken together, the data suggest that [ 123 I]2-INXT may be useful for mapping NET binding sites in the brain

  15. Enkephalin dipeptidyl carboxypeptidase (enkephalinase) activity: selective radioassay, properties, and regional distribution in human brain

    International Nuclear Information System (INIS)

    Llorens, C.; Malfroy, B.; Schwartz, J.C.; Gacel, G.; Roques, B.P.; Roy, J.; Morgat, J.L.; Javoy-Agid, F.; Agid, Y.

    1982-01-01

    The compound [ 3 H-Tyr 1 ,D-Ala 2 ,Leu-OH 5 ]enkephalin has been synthesised as a potentially selective substrate for enkephalin dipeptidyl carboxypeptidase (enkephalinase) activity in brain. Incubations in the presence of homogenates and particulate fractions from rodent and human brain result in the formation of [ 3 H]Tyr-D-Ala-Gly, which can be conveniently isolated by polystyrene bead column chromatography. The enzyme activity responsible for the hydrolysis of the Gly 3 -Phe 4 amide bond of this substrate displays close resemblance to that hydrolysing the natural enkephalins at the same level. In addition, enkephalinase activity characterised in postmortem human brain is closely similar to that in rodent brain, with regard to optimal pH and apparent affinities of various substrates and inhibitors, including the potent compound thiorphan. Enkephalinase activity is distributed in a highly heterogeneous fashion among regions of human brain, the highest levels being found in globus pallidus and pars reticulata of the substantia nigra. This distribution is poorly correlated with that of opiate receptor binding sites but displays some resemblance to that of reported Met 5 -enkephalin levels. (author)

  16. Seasonal expression of arginine vasotocin mRNA and its correlations to gonadal steroidogenic enzymes and sexually dimorphic coloration during sex reversal in the gilthead seabream (Sparus aurata).

    Science.gov (United States)

    Reyes-Tomassini, José J; Wong, Ten-Tsao; Zohar, Yonathan

    2017-06-01

    Arginine vasotocin is a hormone produced in the hypothalamus of teleost fish that has been shown to regulate gonad development and sexual behavior. To study the role of arginine vasotocin in the gonadal cycle of the hermaphrodite gilthead seabream, Sparus aurata, we cloned the seabream arginine vasotocin (avt) complementary DNA (cDNA). We investigated the expression of brain avt throughout the gonad cycle using real-time quantitative PCR and compared its expression levels to the expression levels of two key gonadal steroidogenic enzymes, cyp19a1a and cyp11b2. In July, when the process of sex reversal is thought to begin, avt expression was elevated over the previous 2 months. Avt in the brain remained at or above the level of July until November then peaked again in December. There was no difference between males and females in the expression levels of brain avt throughout the year. However, only in ambisexual fish was the expression of the cyp19a1a gonadal aromatase correlated to the expression of avt in the brain. Cyp11b2 did not show any correlation to brain avt expression. We also found that females had more intense body coloration than males and that this intensity peaked prior to spawning. Avt expression and female coloration were positively correlated. The fact that brain avt expression was lowest during gonad quiescence, together with the observation of a correlation between brain avt with gonadal cyp19a1a and body coloration during that time suggests that avt may play a role during the process of sex reversal and spawning of the gilthead seabream.

  17. Left Brain/Right Brain: Research and Learning. Focused Access to Selected Topics (FAST) Bibliography No. 12.

    Science.gov (United States)

    Eppele, Ruth

    This 27-item bibliography represents the variety of articles added to the ERIC database from 1983 through 1988 on left-brain/right-brain research, theory, and application as it relates to classroom incorporation. Included are conflicting opinions as to the usefulness of left-brain/right-brain studies and their application in the learning…

  18. Can Xanthophyll-Membrane Interactions Explain Their Selective Presence in the Retina and Brain?

    Science.gov (United States)

    Widomska, Justyna; Zareba, Mariusz; Subczynski, Witold Karol

    2016-01-01

    Epidemiological studies demonstrate that a high dietary intake of carotenoids may offer protection against age-related macular degeneration, cancer and cardiovascular and neurodegenerative diseases. Humans cannot synthesize carotenoids and depend on their dietary intake. Major carotenoids that have been found in human plasma can be divided into two groups, carotenes (nonpolar molecules, such as β-carotene, α-carotene or lycopene) and xanthophylls (polar carotenoids that include an oxygen atom in their structure, such as lutein, zeaxanthin and β-cryptoxanthin). Only two dietary carotenoids, namely lutein and zeaxanthin (macular xanthophylls), are selectively accumulated in the human retina. A third carotenoid, meso-zeaxanthin, is formed directly in the human retina from lutein. Additionally, xanthophylls account for about 70% of total carotenoids in all brain regions. Some specific properties of these polar carotenoids must explain why they, among other available carotenoids, were selected during evolution to protect the retina and brain. It is also likely that the selective uptake and deposition of macular xanthophylls in the retina and brain are enhanced by specific xanthophyll-binding proteins. We hypothesize that the high membrane solubility and preferential transmembrane orientation of macular xanthophylls distinguish them from other dietary carotenoids, enhance their chemical and physical stability in retina and brain membranes and maximize their protective action in these organs. Most importantly, xanthophylls are selectively concentrated in the most vulnerable regions of lipid bilayer membranes enriched in polyunsaturated lipids. This localization is ideal if macular xanthophylls are to act as lipid-soluble antioxidants, which is the most accepted mechanism through which lutein and zeaxanthin protect neural tissue against degenerative diseases. PMID:27030822

  19. Can Xanthophyll-Membrane Interactions Explain Their Selective Presence in the Retina and Brain?

    Directory of Open Access Journals (Sweden)

    Justyna Widomska

    2016-01-01

    Full Text Available Epidemiological studies demonstrate that a high dietary intake of carotenoids may offer protection against age-related macular degeneration, cancer and cardiovascular and neurodegenerative diseases. Humans cannot synthesize carotenoids and depend on their dietary intake. Major carotenoids that have been found in human plasma can be divided into two groups, carotenes (nonpolar molecules, such as β-carotene, α-carotene or lycopene and xanthophylls (polar carotenoids that include an oxygen atom in their structure, such as lutein, zeaxanthin and β-cryptoxanthin. Only two dietary carotenoids, namely lutein and zeaxanthin (macular xanthophylls, are selectively accumulated in the human retina. A third carotenoid, meso-zeaxanthin, is formed directly in the human retina from lutein. Additionally, xanthophylls account for about 70% of total carotenoids in all brain regions. Some specific properties of these polar carotenoids must explain why they, among other available carotenoids, were selected during evolution to protect the retina and brain. It is also likely that the selective uptake and deposition of macular xanthophylls in the retina and brain are enhanced by specific xanthophyll-binding proteins. We hypothesize that the high membrane solubility and preferential transmembrane orientation of macular xanthophylls distinguish them from other dietary carotenoids, enhance their chemical and physical stability in retina and brain membranes and maximize their protective action in these organs. Most importantly, xanthophylls are selectively concentrated in the most vulnerable regions of lipid bilayer membranes enriched in polyunsaturated lipids. This localization is ideal if macular xanthophylls are to act as lipid-soluble antioxidants, which is the most accepted mechanism through which lutein and zeaxanthin protect neural tissue against degenerative diseases.

  20. Selection for increased voluntary wheel-running affects behavior and brain monoamines in mice

    Science.gov (United States)

    Waters, R.Parrish; Pringle, R.B.; Forster, G.L.; Renner, K.J.; Malisch, J.L.; Garland, T.; Swallow, J.G.

    2013-01-01

    Selective-breeding of house mice for increased voluntary wheel-running has resulted in multiple physiological and behavioral changes. Characterizing these differences may lead to experimental models that can elucidate factors involved in human diseases and disorders associated with physical inactivity, or potentially treated by physical activity, such as diabetes, obesity, and depression. Herein, we present ethological data for adult males from a line of mice that has been selectively bred for high levels of voluntary wheel-running and from a non-selected control line, housed with or without wheels. Additionally, we present concentrations of central monoamines in limbic, striatal, and midbrain regions. We monitored wheel-running for 8 weeks, and observed home-cage behavior during the last 5 weeks of the study. Mice from the selected line accumulated more revolutions per day than controls due to increased speed and duration of running. Selected mice exhibited more active behaviors than controls, regardless of wheel access, and exhibited less inactivity and grooming than controls. Selective-breeding also influenced the longitudinal patterns of behavior. We found statistically significant differences in monoamine concentrations and associated metabolites in brain regions that influence exercise and motivational state. These results suggest underlying neurochemical differences between selected and control lines that may influence the observed differences in behavior. Our results bolster the argument that selected mice can provide a useful model of human psychological and physiological diseases and disorders. PMID:23352668

  1. Prenatal ethanol exposure alters steroidogenic enzyme activity in newborn rat testes.

    Science.gov (United States)

    Kelce, W R; Rudeen, P K; Ganjam, V K

    1989-10-01

    We have examined the in utero effects of ethanol exposure on testicular steroidogenesis in newborn male pups. Pregnant Sprague-Dawley rats were fed a liquid ethanol diet (35% ethanol-derived calories), a pair-fed isocaloric liquid diet, or a standard laboratory rat chow and water diet beginning on Day 12 of gestation and continuing through parturition. Although there were no significant differences in the enzymatic activity of 5-ene-3 beta-hydroxysteroid dehydrogenase/isomerase or C17,20-lyase, the enzymatic activity of 17 alpha-hydroxylase was significantly (p less than 0.01) reduced (i.e., approximately 36%) in the ethanol-exposed pups compared to those from the pair-fed and chow treatment groups. This lesion in testicular steroidogenic enzyme activity in newborn male pups exposed to alcohol in utero was transient as 17 alpha-hydroxylase activity from the ethanol-exposed animals returned to control levels by postnatal Day 20 and remained at control levels through adulthood (postnatal Day 60). These data suggest that the suppression of the perinatal testosterone surge in male rats exposed to alcohol in utero and the associated long term demasculinizing effects of prenatal ethanol exposure might be the result of reduced testicular steroidogenic enzyme activity in the perinatal animal.

  2. Implications of astrocytes in mediating the protective effects of Selective Estrogen Receptor Modulators upon brain damage

    Directory of Open Access Journals (Sweden)

    George E. Barreto

    2015-04-01

    Full Text Available Selective Estrogen Receptor Modulators (SERMs are steroidal or non-steroidal compounds that are already used in clinical practice for the treatment of breast cancer, osteoporosis and menopausal symptoms. While SERMs actions in the breast, bone, and uterus have been well characterized, their actions in the brain are less well understood. Previous works have demonstrated the beneficial effects of SERMs in different chronic neurodegenerative diseases like Alzheimer, Parkinson’s disease and Multiple sclerosis, as well as acute degeneration as stroke and traumatic brain injury. Moreover, these compounds exhibit similar protective actions as those of estradiol in the Central Nervous System, overt any secondary effect. For these reasons, in the past few years, there has been a growing interest in the neuroprotective effects exerted directly or indirectly by SERMs in the SNC. In this context, astrocytes play an important role in the maintenance of brain metabolism, and antioxidant support to neurons, thus indicating that better protection of astrocytes are an important asset targeting neuronal protection. Moreover, various clinical and experimental studies have reported that astrocytes are essential for the neuroprotective effects of SERMs during neuronal injuries, as these cells express different estrogen receptors in cell membrane, demonstrating that part of SERMs effects upon injury may be mediated by astrocytes. The present work highlights the current evidence on the protective mechanisms of SERMs, such as tamoxifen and raloxifene, in the SNC, and their modulation of astrocytic properties as promising therapeutic targets during brain damage.

  3. Brain activity during divided and selective attention to auditory and visual sentence comprehension tasks.

    Science.gov (United States)

    Moisala, Mona; Salmela, Viljami; Salo, Emma; Carlson, Synnöve; Vuontela, Virve; Salonen, Oili; Alho, Kimmo

    2015-01-01

    Using functional magnetic resonance imaging (fMRI), we measured brain activity of human participants while they performed a sentence congruence judgment task in either the visual or auditory modality separately, or in both modalities simultaneously. Significant performance decrements were observed when attention was divided between the two modalities compared with when one modality was selectively attended. Compared with selective attention (i.e., single tasking), divided attention (i.e., dual-tasking) did not recruit additional cortical regions, but resulted in increased activity in medial and lateral frontal regions which were also activated by the component tasks when performed separately. Areas involved in semantic language processing were revealed predominantly in the left lateral prefrontal cortex by contrasting incongruent with congruent sentences. These areas also showed significant activity increases during divided attention in relation to selective attention. In the sensory cortices, no crossmodal inhibition was observed during divided attention when compared with selective attention to one modality. Our results suggest that the observed performance decrements during dual-tasking are due to interference of the two tasks because they utilize the same part of the cortex. Moreover, semantic dual-tasking did not appear to recruit additional brain areas in comparison with single tasking, and no crossmodal inhibition was observed during intermodal divided attention.

  4. Brain activity during divided and selective attention to auditory and visual sentence comprehension tasks

    Science.gov (United States)

    Moisala, Mona; Salmela, Viljami; Salo, Emma; Carlson, Synnöve; Vuontela, Virve; Salonen, Oili; Alho, Kimmo

    2015-01-01

    Using functional magnetic resonance imaging (fMRI), we measured brain activity of human participants while they performed a sentence congruence judgment task in either the visual or auditory modality separately, or in both modalities simultaneously. Significant performance decrements were observed when attention was divided between the two modalities compared with when one modality was selectively attended. Compared with selective attention (i.e., single tasking), divided attention (i.e., dual-tasking) did not recruit additional cortical regions, but resulted in increased activity in medial and lateral frontal regions which were also activated by the component tasks when performed separately. Areas involved in semantic language processing were revealed predominantly in the left lateral prefrontal cortex by contrasting incongruent with congruent sentences. These areas also showed significant activity increases during divided attention in relation to selective attention. In the sensory cortices, no crossmodal inhibition was observed during divided attention when compared with selective attention to one modality. Our results suggest that the observed performance decrements during dual-tasking are due to interference of the two tasks because they utilize the same part of the cortex. Moreover, semantic dual-tasking did not appear to recruit additional brain areas in comparison with single tasking, and no crossmodal inhibition was observed during intermodal divided attention. PMID:25745395

  5. Goal selection versus process control while learning to use a brain-computer interface

    Science.gov (United States)

    Royer, Audrey S.; Rose, Minn L.; He, Bin

    2011-06-01

    A brain-computer interface (BCI) can be used to accomplish a task without requiring motor output. Two major control strategies used by BCIs during task completion are process control and goal selection. In process control, the user exerts continuous control and independently executes the given task. In goal selection, the user communicates their goal to the BCI and then receives assistance executing the task. A previous study has shown that goal selection is more accurate and faster in use. An unanswered question is, which control strategy is easier to learn? This study directly compares goal selection and process control while learning to use a sensorimotor rhythm-based BCI. Twenty young healthy human subjects were randomly assigned either to a goal selection or a process control-based paradigm for eight sessions. At the end of the study, the best user from each paradigm completed two additional sessions using all paradigms randomly mixed. The results of this study were that goal selection required a shorter training period for increased speed, accuracy, and information transfer over process control. These results held for the best subjects as well as in the general subject population. The demonstrated characteristics of goal selection make it a promising option to increase the utility of BCIs intended for both disabled and able-bodied users.

  6. Automatic motor task selection via a bandit algorithm for a brain-controlled button

    Science.gov (United States)

    Fruitet, Joan; Carpentier, Alexandra; Munos, Rémi; Clerc, Maureen

    2013-02-01

    Objective. Brain-computer interfaces (BCIs) based on sensorimotor rhythms use a variety of motor tasks, such as imagining moving the right or left hand, the feet or the tongue. Finding the tasks that yield best performance, specifically to each user, is a time-consuming preliminary phase to a BCI experiment. This study presents a new adaptive procedure to automatically select (online) the most promising motor task for an asynchronous brain-controlled button. Approach. We develop for this purpose an adaptive algorithm UCB-classif based on the stochastic bandit theory and design an EEG experiment to test our method. We compare (offline) the adaptive algorithm to a naïve selection strategy which uses uniformly distributed samples from each task. We also run the adaptive algorithm online to fully validate the approach. Main results. By not wasting time on inefficient tasks, and focusing on the most promising ones, this algorithm results in a faster task selection and a more efficient use of the BCI training session. More precisely, the offline analysis reveals that the use of this algorithm can reduce the time needed to select the most appropriate task by almost half without loss in precision, or alternatively, allow us to investigate twice the number of tasks within a similar time span. Online tests confirm that the method leads to an optimal task selection. Significance. This study is the first one to optimize the task selection phase by an adaptive procedure. By increasing the number of tasks that can be tested in a given time span, the proposed method could contribute to reducing ‘BCI illiteracy’.

  7. Selective Estrogen Receptor Modulators regulate reactive microglia after penetrating brain injury

    Directory of Open Access Journals (Sweden)

    George E. Barreto

    2014-06-01

    Full Text Available Following brain injury, microglia assume a reactive-like state and secrete pro-inflammatory molecules that can potentiate damage. A therapeutic strategy that may limit microgliosis is of potential interest. In this context, selective estrogen receptor modulators, such as raloxifene and tamoxifen, are known to reduce microglia activation induced by neuroinflammatory stimuli in young animals. In the present study, we have assessed whether raloxifene and tamoxifen are able to affect microglia activation after brain injury in young and aged animals in time points relevant to clinics, which is hours after brain trauma. Volume fraction of MHC-II+ microglia was estimated according to the point-counting method of Weibel within a distance of 350 μm from the lateral border of the wound, and cellular morphology was measured by fractal analysis. Two groups of animals were studied: 1 young rats, ovariectomized at 2 months of age; and 2 aged rats, ovariectomized at 18 months of age. Fifteen days after ovariectomy animals received a stab wound brain injury and the treatment with estrogenic compounds. Our findings indicate that raloxifene and tamoxifen reduced microglia activation in both young and aged animals. Although the volume fraction of reactive microglia was found lower in aged animals, this was accompanied by important changes in cell morphology, where aged microglia assume a bushier and hyperplasic aspect when compared to young microglia. These data suggest that early regulation of microglia activation provides a mechanism by which SERMs may exert a neuroprotective effect in the setting of a brain trauma.

  8. Selective binding of 2-[{sup 125}I]iodo-nisoxetine to norepinephrine transporters in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Kung, M.-P.; Choi, Seok-Rye; Hou, Catherine; Zhuang, Z.-P.; Foulon, Catherine; Kung, Hank F. E-mail: kunghf@sunmac.spect.upenn.edu

    2004-07-01

    A radioiodinated ligand, (R)-N-methyl-(2-[{sup 125}I]iodo-phenoxy)-3-phenylpropylamine, [{sup 125}I]2-INXT, targeting norepinephrine transporters (NET), was successfully prepared. A no-carrier-added product, [{sup 125}I]2-INXT, displayed a saturable binding with a high affinity (K{sub d}=0.06 nM) in the homogenates prepared from rat cortical tissues as well as from LLC-PK{sub 1} cells expressing NET. A relatively low number of binding sties (B{sub max}=55 fmol/mg protein) measured with [{sup 125}I]2-INXT in rat cortical homogenates is consistent with the value reported for a known NET ligand, [{sup 3}H]nisoxetine. Competition studies with various compounds on [{sup 125}I]2-INXT binding clearly confirmed the pharmacological specificity and selectivity for NET binding sites. Following a tail-vein injection of [{sup 125}I]2-INXT in rats, a good initial brain uptake was observed (0.56% dose at 2 min) followed by a slow washout from the brain (0.2% remained at 3 hours post-injection). The hypothalamus (a NET-rich region) to striatum (a region devoid of NET) ratio was 1.5 at 3 hours post-i.v. injection. Pretreatment of rats with nisoxetine significantly inhibited the uptake of [{sup 125}I]2-INXT (70-100% inhibition) in locus coeruleus, hypothalamus and raphe nuclei, regions known to have a high density of NET; whereas escitalopram, a serotonin transporter ligand, did not show a similar effect. Ex vivo autoradiography of rat brain sections of [{sup 125}I]2-INXT (at 3 hours after an i.v. injection) displayed an excellent regional brain localization pattern corroborated to the specific NET distribution in the brain. The specific brain localization was significantly reduced by a dose of nisoxetine pretreatment. Taken together, the data suggest that [{sup 123}I]2-INXT may be useful for mapping NET binding sites in the brain.

  9. No relationship between most polymorphisms of steroidogenic acute regulatory (StAR gene with polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Azadeh-Sadat Nazouri

    2015-12-01

    Full Text Available Background: Polycystic ovary syndrome (PCOS is one of the most common endocrine women’s disorders in reproductive age. Hyperandrogenism has a critical role in the etiology of PCOS and it can cause fault in Steroidogenesis process. During steroidogenesis, steroidogenic acute regulatory protein (StAR seems to increase the delivery of cholesterol through mitochondrial membrane. Therefore, polymorphisms of StAR might effect on this protein and play a role in the etiology of PCOS. Objective: The aim of this study was to investigate the association between StAR SNPs with PCOS. Thus, seven polymorphisms in this gene: rs104894086, rs104894089, rs104894090, rs137852689, rs10489487, rs104894085 were detected. Materials and Methods: In this case control study, 45 PCOS women, 40 male factor/unexplained infertile women, and 40 fertile women as two control groups were participated from 2008-2012. Polymorphisms were detected using restriction fragment length polymorphism (PCR-RFLP method. Results: Heterozygote genotyping for rs137852689 SNP (amino acid 218 C > T was only seen in seven PCOS patients, one in normal ovulatory women, and five in male factor/unexplained infertile women (15.5%, 2.5%, 12.5%, respectively (p= 0.12. While, it has shown no association between other SNPS with PCOs. Conclusion: The RFLP results for seven chosen SNPs, which located in exon 5 and 7 showed normal status in three groups, it means no heterozygous or homozygous forms of selected SNPs were observed. So, it seems evaluation of the active amino acid sites should be investigated and also the study population should be increased.

  10. Design and in vivo evaluation of more efficient and selective deep brain stimulation electrodes

    Science.gov (United States)

    Howell, Bryan; Huynh, Brian; Grill, Warren M.

    2015-08-01

    Objective. Deep brain stimulation (DBS) is an effective treatment for movement disorders and a promising therapy for treating epilepsy and psychiatric disorders. Despite its clinical success, the efficiency and selectivity of DBS can be improved. Our objective was to design electrode geometries that increased the efficiency and selectivity of DBS. Approach. We coupled computational models of electrodes in brain tissue with cable models of axons of passage (AOPs), terminating axons (TAs), and local neurons (LNs); we used engineering optimization to design electrodes for stimulating these neural elements; and the model predictions were tested in vivo. Main results. Compared with the standard electrode used in the Medtronic Model 3387 and 3389 arrays, model-optimized electrodes consumed 45-84% less power. Similar gains in selectivity were evident with the optimized electrodes: 50% of parallel AOPs could be activated while reducing activation of perpendicular AOPs from 44 to 48% with the standard electrode to 0-14% with bipolar designs; 50% of perpendicular AOPs could be activated while reducing activation of parallel AOPs from 53 to 55% with the standard electrode to 1-5% with an array of cathodes; and, 50% of TAs could be activated while reducing activation of AOPs from 43 to 100% with the standard electrode to 2-15% with a distal anode. In vivo, both the geometry and polarity of the electrode had a profound impact on the efficiency and selectivity of stimulation. Significance. Model-based design is a powerful tool that can be used to improve the efficiency and selectivity of DBS electrodes.

  11. Selective attention to affective value alters how the brain processes olfactory stimuli.

    Science.gov (United States)

    Rolls, Edmund T; Grabenhorst, Fabian; Margot, Christian; da Silva, Maria A A P; Velazco, Maria Ines

    2008-10-01

    How does selective attention to affect influence sensory processing? In a functional magnetic resonance imaging investigation, when subjects were instructed to remember and rate the pleasantness of a jasmine odor, activations were greater in the medial orbito-frontal and pregenual cingulate cortex than when subjects were instructed to remember and rate the intensity of the odor. When the subjects were instructed to remember and rate the intensity, activations were greater in the inferior frontal gyrus. These top-down effects occurred not only during odor delivery but started in a preparation period after the instruction before odor delivery, and continued after termination of the odor in a short-term memory period. Thus, depending on the context in which odors are presented and whether affect is relevant, the brain prepares itself, responds to, and remembers an odor differently. These findings show that when attention is paid to affective value, the brain systems engaged to prepare for, represent, and remember a sensory stimulus are different from those engaged when attention is directed to the physical properties of a stimulus such as its intensity. This differential biasing of brain regions engaged in processing a sensory stimulus depending on whether the cognitive demand is for affect-related versus more sensory-related processing may be an important aspect of cognition and attention. This has many implications for understanding the effects not only of olfactory but also of other sensory stimuli.

  12. Selective sensation based brain-computer interface via mechanical vibrotactile stimulation.

    Science.gov (United States)

    Yao, Lin; Meng, Jianjun; Zhang, Dingguo; Sheng, Xinjun; Zhu, Xiangyang

    2013-01-01

    In this work, mechanical vibrotactile stimulation was applied to subjects' left and right wrist skins with equal intensity, and a selective sensation perception task was performed to achieve two types of selections similar to motor imagery Brain-Computer Interface. The proposed system was based on event-related desynchronization/synchronization (ERD/ERS), which had a correlation with processing of afferent inflow in human somatosensory system, and attentional effect which modulated the ERD/ERS. The experiments were carried out on nine subjects (without experience in selective sensation), and six of them showed a discrimination accuracy above 80%, three of them above 95%. Comparative experiments with motor imagery (with and without presence of stimulation) were also carried out, which further showed the feasibility of selective sensation as an alternative BCI task complementary to motor imagery. Specifically there was significant improvement ([Formula: see text]) from near 65% in motor imagery (with and without presence of stimulation) to above 80% in selective sensation on some subjects. The proposed BCI modality might well cooperate with existing BCI modalities in the literature in enlarging the widespread usage of BCI system.

  13. A four-dimensional virtual hand brain-machine interface using active dimension selection.

    Science.gov (United States)

    Rouse, Adam G

    2016-06-01

    Brain-machine interfaces (BMI) traditionally rely on a fixed, linear transformation from neural signals to an output state-space. In this study, the assumption that a BMI must control a fixed, orthogonal basis set was challenged and a novel active dimension selection (ADS) decoder was explored. ADS utilizes a two stage decoder by using neural signals to both (i) select an active dimension being controlled and (ii) control the velocity along the selected dimension. ADS decoding was tested in a monkey using 16 single units from premotor and primary motor cortex to successfully control a virtual hand avatar to move to eight different postures. Following training with the ADS decoder to control 2, 3, and then 4 dimensions, each emulating a grasp shape of the hand, performance reached 93% correct with a bit rate of 2.4 bits s(-1) for eight targets. Selection of eight targets using ADS control was more efficient, as measured by bit rate, than either full four-dimensional control or computer assisted one-dimensional control. ADS decoding allows a user to quickly and efficiently select different hand postures. This novel decoding scheme represents a potential method to reduce the complexity of high-dimension BMI control of the hand.

  14. Selective Sensation Based Brain-Computer Interface via Mechanical Vibrotactile Stimulation

    Science.gov (United States)

    Yao, Lin; Meng, Jianjun; Zhang, Dingguo; Sheng, Xinjun; Zhu, Xiangyang

    2013-01-01

    In this work, mechanical vibrotactile stimulation was applied to subjects’ left and right wrist skins with equal intensity, and a selective sensation perception task was performed to achieve two types of selections similar to motor imagery Brain-Computer Interface. The proposed system was based on event-related desynchronization/synchronization (ERD/ERS), which had a correlation with processing of afferent inflow in human somatosensory system, and attentional effect which modulated the ERD/ERS. The experiments were carried out on nine subjects (without experience in selective sensation), and six of them showed a discrimination accuracy above 80%, three of them above 95%. Comparative experiments with motor imagery (with and without presence of stimulation) were also carried out, which further showed the feasibility of selective sensation as an alternative BCI task complementary to motor imagery. Specifically there was significant improvement () from near 65% in motor imagery (with and without presence of stimulation) to above 80% in selective sensation on some subjects. The proposed BCI modality might well cooperate with existing BCI modalities in the literature in enlarging the widespread usage of BCI system. PMID:23762253

  15. Immunohistochemical evaluation of proliferation, apoptosis and steroidogenic enzymes in the ovary of rats with polycystic ovary.

    Science.gov (United States)

    Lombardi, Leonardo Augusto; Simões, Ricardo Santos; Maganhin, Carla Cristina; Baracat, Maria Cândida Pinheiro; Silva-Sasso, Gisela Rodrigues; Florencio-Silva, Rinaldo; Soares, José Maria; Baracat, Edmund Chada

    2014-07-01

    to evaluate the immunohistochemical expression of proliferative, apoptotic and steroidogenic enzyme markers in the ovaries of rats with polycystic ovary syndrome (PCOS). twenty rats were divided into two groups: GCtrl - estrous phase, and PCOS - with polycystic ovaries. The GCtrl animals were subjected to a lighting period from 7 am to 7 pm, while the animals with PCOS group remained with continuous lighting for 60 days. Subsequently, the animals were anesthetized, the ovaries were removed and fixed in 10% formaldehyde, prior to paraffin embedding. Sections were stained using H.E. or subjected to immunohistochemical methods for the detection of Ki-67, cleaved caspase-3, CYP11A1, CYP17A1 and CYP19A1. The results were analyzed using Student's t-test (p ovaries of rats with PCOS, responsible for the high levels of androgens and estradiol.

  16. The optimal hormonal replacement modality selection for multiple organ procurement from brain-dead organ donors

    Directory of Open Access Journals (Sweden)

    Mi Z

    2014-12-01

    Full Text Available Zhibao Mi,1 Dimitri Novitzky,2 Joseph F Collins,1 David KC Cooper3 1Cooperative Studies Program Coordinating Center, VA Maryland Health Care Systems, Perry Point, MD, USA; 2Department of Cardiothoracic Surgery, University of South Florida, Tampa, FL, USA; 3Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA Abstract: The management of brain-dead organ donors is complex. The use of inotropic agents and replacement of depleted hormones (hormonal replacement therapy is crucial for successful multiple organ procurement, yet the optimal hormonal replacement has not been identified, and the statistical adjustment to determine the best selection is not trivial. Traditional pair-wise comparisons between every pair of treatments, and multiple comparisons to all (MCA, are statistically conservative. Hsu’s multiple comparisons with the best (MCB – adapted from the Dunnett’s multiple comparisons with control (MCC – has been used for selecting the best treatment based on continuous variables. We selected the best hormonal replacement modality for successful multiple organ procurement using a two-step approach. First, we estimated the predicted margins by constructing generalized linear models (GLM or generalized linear mixed models (GLMM, and then we applied the multiple comparison methods to identify the best hormonal replacement modality given that the testing of hormonal replacement modalities is independent. Based on 10-year data from the United Network for Organ Sharing (UNOS, among 16 hormonal replacement modalities, and using the 95% simultaneous confidence intervals, we found that the combination of thyroid hormone, a corticosteroid, antidiuretic hormone, and insulin was the best modality for multiple organ procurement for transplantation. Keywords: best treatment selection, brain-dead organ donors, hormonal replacement, multiple binary endpoints, organ procurement, multiple comparisons

  17. Developmental programming: prenatal steroid excess disrupts key members of intraovarian steroidogenic pathway in sheep.

    Science.gov (United States)

    Padmanabhan, Vasantha; Salvetti, Natalia R; Matiller, Valentina; Ortega, Hugo H

    2014-09-01

    Prenatal testosterone (T) excess disrupts ovarian cyclicity and increases circulating estradiol levels as well as follicular recruitment and persistence culminating in multifollicular ovary similar to women with polycystic ovary syndrome. We tested whether prenatal T excess, by androgenic or estrogenic action, disrupts the steroid biosynthetic machinery in sheep in a cell-, follicle stage-, age-, and treatment-specific manner consistent with the ovarian disruptions and increased estradiol release. Impact of T/dihydrotestosterone (DHT) treatments from days 30-90 of gestation on steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase, cytochrome P-450 17α-hydroxylase/C17, 20-lyase (CYP17A1), and cytochrome P-450 aromatase (CYP19A1) were examined on fetal day 90, 140 and 10 months (postpubertal), and 21 months (adult, no DHT group) of age by immunohistochemistry. All 4 markers changed in a cell-, follicle stage-, and age-specific manner. Both treatments increased steroidogenic acute regulatory protein expression in preantral follicles of postpubertal and adult females. Effects of prenatal T and DHT on 3β-hydroxysteroid dehydrogenase differed in a follicle- and age-specific manner. CYP17A1 was reduced in the theca interna of antral follicles by T, but not DHT, in 10- and 21-month-old females. CYP19A1 was reduced by both T and DHT at all ages barring an increase on fetal day 140. Reduced granulosa CYP19A1 and thecal CYP17A1 in adults likely disrupt the intrafollicular androgen/estrogen balance contributing to follicular persistence. The reduced thecal CYP17A1 expression suggests that the hyperandrogenic ovarian phenotype may originate from increased enzyme activity or alternatively via a different isoform of CYP17. The reduced CYP19A1 in antral follicles of adults indicates that the increased circulating estradiol release likely arises from the increased number of persisting follicles.

  18. Genistein promotes DNA demethylation of the steroidogenic factor 1 (SF-1) promoter in endometrial stromal cells

    International Nuclear Information System (INIS)

    Matsukura, Hiroshi; Aisaki, Ken-ichi; Igarashi, Katsuhide; Matsushima, Yuko; Kanno, Jun; Muramatsu, Masaaki; Sudo, Katsuko; Sato, Noriko

    2011-01-01

    Highlights: → Genistein (GEN) is a phytoestrogen found in soy products. → GEN demethylated/unsilenced the steroidogenic factor 1 gene in endometrial tissue. → GEN thus altered mRNA expression in uteri of ovariectomized (OVX) mice. → A high-resolution melting assay was used to screen for epigenetic change. → We isolated an endometrial cell clone that was epigenetically modulated by GEN. -- Abstract: It has recently been demonstrated that genistein (GEN), a phytoestrogen in soy products, is an epigenetic modulator in various types of cells; but its effect on endometrium has not yet been determined. We investigated the effects of GEN on mouse uterine cells, in vivo and in vitro. Oral administration of GEN for 1 week induced mild proliferation of the endometrium in ovariectomized (OVX) mice, which was accompanied by the induction of steroidogenic factor 1 (SF-1) gene expression. GEN administration induced demethylation of multiple CpG sites in the SF-1 promoter; these sites are extensively methylated and thus silenced in normal endometrium. The GEN-mediated promoter demethylation occurred predominantly on the luminal side, as opposed to myometrium side, indicating that the epigenetic change was mainly shown in regenerated cells. Primary cultures of endometrial stromal cell colonies were screened for GEN-mediated alterations of DNA methylation by a high-resolution melting (HRM) method. One out of 20 colony-forming cell clones showed GEN-induced demethylation of SF-1. This clone exhibited a high proliferation capacity with continuous colony formation activity through multiple serial clonings. We propose that only a portion of endometrial cells are capable of receiving epigenetic modulation by GEN.

  19. Genistein promotes DNA demethylation of the steroidogenic factor 1 (SF-1) promoter in endometrial stromal cells

    Energy Technology Data Exchange (ETDEWEB)

    Matsukura, Hiroshi, E-mail: hmatsukura.epi@mri.tmd.ac.jp [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Aisaki, Ken-ichi; Igarashi, Katsuhide; Matsushima, Yuko; Kanno, Jun [Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Muramatsu, Masaaki [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Sudo, Katsuko [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Animal Research Center, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402 (Japan); Sato, Noriko, E-mail: nsato.epi@tmd.ac.jp [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan)

    2011-08-26

    Highlights: {yields} Genistein (GEN) is a phytoestrogen found in soy products. {yields} GEN demethylated/unsilenced the steroidogenic factor 1 gene in endometrial tissue. {yields} GEN thus altered mRNA expression in uteri of ovariectomized (OVX) mice. {yields} A high-resolution melting assay was used to screen for epigenetic change. {yields} We isolated an endometrial cell clone that was epigenetically modulated by GEN. -- Abstract: It has recently been demonstrated that genistein (GEN), a phytoestrogen in soy products, is an epigenetic modulator in various types of cells; but its effect on endometrium has not yet been determined. We investigated the effects of GEN on mouse uterine cells, in vivo and in vitro. Oral administration of GEN for 1 week induced mild proliferation of the endometrium in ovariectomized (OVX) mice, which was accompanied by the induction of steroidogenic factor 1 (SF-1) gene expression. GEN administration induced demethylation of multiple CpG sites in the SF-1 promoter; these sites are extensively methylated and thus silenced in normal endometrium. The GEN-mediated promoter demethylation occurred predominantly on the luminal side, as opposed to myometrium side, indicating that the epigenetic change was mainly shown in regenerated cells. Primary cultures of endometrial stromal cell colonies were screened for GEN-mediated alterations of DNA methylation by a high-resolution melting (HRM) method. One out of 20 colony-forming cell clones showed GEN-induced demethylation of SF-1. This clone exhibited a high proliferation capacity with continuous colony formation activity through multiple serial clonings. We propose that only a portion of endometrial cells are capable of receiving epigenetic modulation by GEN.

  20. An independent brain-computer interface using covert non-spatial visual selective attention

    Science.gov (United States)

    Zhang, Dan; Maye, Alexander; Gao, Xiaorong; Hong, Bo; Engel, Andreas K.; Gao, Shangkai

    2010-02-01

    In this paper, a novel independent brain-computer interface (BCI) system based on covert non-spatial visual selective attention of two superimposed illusory surfaces is described. Perception of two superimposed surfaces was induced by two sets of dots with different colors rotating in opposite directions. The surfaces flickered at different frequencies and elicited distinguishable steady-state visual evoked potentials (SSVEPs) over parietal and occipital areas of the brain. By selectively attending to one of the two surfaces, the SSVEP amplitude at the corresponding frequency was enhanced. An online BCI system utilizing the attentional modulation of SSVEP was implemented and a 3-day online training program with healthy subjects was carried out. The study was conducted with Chinese subjects at Tsinghua University, and German subjects at University Medical Center Hamburg-Eppendorf (UKE) using identical stimulation software and equivalent technical setup. A general improvement of control accuracy with training was observed in 8 out of 18 subjects. An averaged online classification accuracy of 72.6 ± 16.1% was achieved on the last training day. The system renders SSVEP-based BCI paradigms possible for paralyzed patients with substantial head or ocular motor impairments by employing covert attention shifts instead of changing gaze direction.

  1. Visual encoding and fixation target selection in free viewing: presaccadic brain potentials

    Directory of Open Access Journals (Sweden)

    Andrey R Nikolaev

    2013-06-01

    Full Text Available In scrutinizing a scene, the eyes alternate between fixations and saccades. During a fixation, two component processes can be distinguished: visual encoding and selection of the next fixation target. We aimed to distinguish the neural correlates of these processes in the electrical brain activity prior to a saccade onset. Participants viewed color photographs of natural scenes, in preparation for a change detection task. Then, for each participant and each scene we computed an image heat map, with temperature representing the duration and density of fixations. The temperature difference between the start and end points of saccades was taken as a measure of the expected task-relevance of the information concentrated in specific regions of a scene. Visual encoding was evaluated according to whether subsequent change was correctly detected. Saccades with larger temperature difference were more likely to be followed by correct detection than ones with smaller temperature differences. The amplitude of presaccadic activity over anterior brain areas was larger for correct detection than for detection failure. This difference was observed for short scrutinizing but not for long explorative saccades, suggesting that presaccadic activity reflects top-down saccade guidance. Thus, successful encoding requires local scanning of scene regions which are expected to be task-relevant. Next, we evaluated fixation target selection. Saccades moving up in temperature were preceded by presaccadic activity of higher amplitude than those moving down. This finding suggests that presaccadic activity reflects attention deployed to the following fixation location. Our findings illustrate how presaccadic activity can elucidate concurrent brain processes related to the immediate goal of planning the next saccade and the larger-scale goal of constructing a robust representation of the visual scene.

  2. Towards 1H-MRSI of the human brain at 7T with slice-selective adiabatic refocusing pulses.

    NARCIS (Netherlands)

    Scheenen, T.W.J.; Heerschap, A.; Klomp, D.W.J.

    2008-01-01

    OBJECTIVE: To explore the possibilities of proton spectroscopic imaging (1H-MRSI) of the human brain at 7 Tesla with adiabatic refocusing pulses. MATERIALS AND METHODS: A combination of conventional slice selective excitation and two pairs of slice selective adiabatic refocusing pulses (semi-LASER)

  3. Face and Word Recognition Can Be Selectively Affected by Brain Injury or Developmental Disorders.

    Science.gov (United States)

    Robotham, Ro J; Starrfelt, Randi

    2017-01-01

    Face and word recognition have traditionally been thought to rely on highly specialised and relatively independent cognitive processes. Some of the strongest evidence for this has come from patients with seemingly category-specific visual perceptual deficits such as pure prosopagnosia, a selective face recognition deficit, and pure alexia, a selective word recognition deficit. Together, the patterns of impaired reading with preserved face recognition and impaired face recognition with preserved reading constitute a double dissociation. The existence of these selective deficits has been questioned over the past decade. It has been suggested that studies describing patients with these pure deficits have failed to measure the supposedly preserved functions using sensitive enough measures, and that if tested using sensitive measurements, all patients with deficits in one visual category would also have deficits in the other. The implications of this would be immense, with most textbooks in cognitive neuropsychology requiring drastic revisions. In order to evaluate the evidence for dissociations, we review studies that specifically investigate whether face or word recognition can be selectively affected by acquired brain injury or developmental disorders. We only include studies published since 2004, as comprehensive reviews of earlier studies are available. Most of the studies assess the supposedly preserved functions using sensitive measurements. We found convincing evidence that reading can be preserved in acquired and developmental prosopagnosia and also evidence (though weaker) that face recognition can be preserved in acquired or developmental dyslexia, suggesting that face and word recognition are at least in part supported by independent processes.

  4. Optimization of selective inversion recovery magnetization transfer imaging for macromolecular content mapping in the human brain.

    Science.gov (United States)

    Dortch, Richard D; Bagnato, Francesca; Gochberg, Daniel F; Gore, John C; Smith, Seth A

    2018-03-24

    To optimize a selective inversion recovery (SIR) sequence for macromolecular content mapping in the human brain at 3.0T. SIR is a quantitative method for measuring magnetization transfer (qMT) that uses a low-power, on-resonance inversion pulse. This results in a biexponential recovery of free water signal that can be sampled at various inversion/predelay times (t I/ t D ) to estimate a subset of qMT parameters, including the macromolecular-to-free pool-size-ratio (PSR), the R 1 of free water (R 1f ), and the rate of MT exchange (k mf ). The adoption of SIR has been limited by long acquisition times (≈4 min/slice). Here, we use Cramér-Rao lower bound theory and data reduction strategies to select optimal t I /t D combinations to reduce imaging times. The schemes were experimentally validated in phantoms, and tested in healthy volunteers (N = 4) and a multiple sclerosis patient. Two optimal sampling schemes were determined: (i) a 5-point scheme (k mf estimated) and (ii) a 4-point scheme (k mf assumed). In phantoms, the 5/4-point schemes yielded parameter estimates with similar SNRs as our previous 16-point scheme, but with 4.1/6.1-fold shorter scan times. Pair-wise comparisons between schemes did not detect significant differences for any scheme/parameter. In humans, parameter values were consistent with published values, and similar levels of precision were obtained from all schemes. Furthermore, fixing k mf reduced the sensitivity of PSR to partial-volume averaging, yielding more consistent estimates throughout the brain. qMT parameters can be robustly estimated in ≤1 min/slice (without independent measures of ΔB 0 , B1+, and T 1 ) when optimized t I -t D combinations are selected. © 2018 International Society for Magnetic Resonance in Medicine.

  5. Aspartic acid-promoted highly selective and sensitive colorimetric sensing of cysteine in rat brain.

    Science.gov (United States)

    Qian, Qin; Deng, Jingjing; Wang, Dalei; Yang, Lifen; Yu, Ping; Mao, Lanqun

    2012-11-06

    Direct selective determination of cysteine in the cerebral system is of great importance because of the crucial roles of cysteine in physiological and pathological processes. In this study, we report a sensitive and selective colorimetric assay for cysteine in the rat brain with gold nanoparticles (Au-NPs) as the signal readout. Initially, Au-NPs synthesized with citrate as the stabilizer are red in color and exhibit absorption at 520 nm. The addition of an aqueous solution (20 μL) of cysteine or aspartic acid alone to a 200 μL Au-NP dispersion causes no aggregation, while the addition of an aqueous solution of cysteine into a Au-NP dispersion containing aspartic acid (1.8 mM) causes the aggregation of Au-NPs and thus results in the color change of the colloid from wine red to blue. These changes are ascribed to the ion pair interaction between aspartic acid and cysteine on the interface between Au-NPs and solution. The concentration of cysteine can be visualized with the naked eye and determined by UV-vis spectroscopy. The signal output shows a linear relationship for cysteine within the concentration range from 0.166 to 1.67 μM with a detection limit of 100 nM. The assay demonstrated here is highly selective and is free from the interference of other natural amino acids and other thiol-containing species as well as the species commonly existing in the brain such as lactate, ascorbic acid, and glucose. The basal dialysate level of cysteine in the microdialysate from the striatum of adult male Sprague-Dawley rats is determined to be around 9.6 ± 2.1 μM. The method demonstrated here is facile but reliable and durable and is envisaged to be applicable to understanding the chemical essence involved in physiological and pathological events associated with cysteine.

  6. Selective insulin resistance in homeostatic and cognitive control brain areas in overweight and obese adults.

    Science.gov (United States)

    Kullmann, Stephanie; Heni, Martin; Veit, Ralf; Scheffler, Klaus; Machann, Jürgen; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

    2015-06-01

    Impaired brain insulin action has been linked to obesity, type 2 diabetes, and neurodegenerative diseases. To date, the central nervous effects of insulin in obese humans still remain ill defined, and no study thus far has evaluated the specific brain areas affected by insulin resistance. In 25 healthy lean and 23 overweight/obese participants, we performed magnetic resonance imaging to measure cerebral blood flow (CBF) before and 15 and 30 min after application of intranasal insulin or placebo. Additionally, participants explicitly rated pictures of high-caloric savory and sweet food 60 min after the spray for wanting and liking. In response to insulin compared with placebo, we found a significant CBF decrease in the hypothalamus in both lean and overweight/obese participants. The magnitude of this response correlated with visceral adipose tissue independent of other fat compartments. Furthermore, we observed a differential response in the lean compared with the overweight/obese group in the prefrontal cortex, resulting in an insulin-induced CBF reduction in lean participants only. This prefrontal cortex response significantly correlated with peripheral insulin sensitivity and eating behavior measures such as disinhibition and food craving. Behaviorally, we were able to observe a significant reduction for the wanting of sweet foods after insulin application in lean men only. Brain insulin action was selectively impaired in the prefrontal cortex in overweight and obese adults and in the hypothalamus in participants with high visceral adipose tissue, potentially promoting an altered homeostatic set point and reduced inhibitory control contributing to overeating behavior. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  7. Tensor-based Multi-view Feature Selection with Applications to Brain Diseases

    Science.gov (United States)

    Cao, Bokai; He, Lifang; Kong, Xiangnan; Yu, Philip S.; Hao, Zhifeng; Ragin, Ann B.

    2015-01-01

    In the era of big data, we can easily access information from multiple views which may be obtained from different sources or feature subsets. Generally, different views provide complementary information for learning tasks. Thus, multi-view learning can facilitate the learning process and is prevalent in a wide range of application domains. For example, in medical science, measurements from a series of medical examinations are documented for each subject, including clinical, imaging, immunologic, serologic and cognitive measures which are obtained from multiple sources. Specifically, for brain diagnosis, we can have different quantitative analysis which can be seen as different feature subsets of a subject. It is desirable to combine all these features in an effective way for disease diagnosis. However, some measurements from less relevant medical examinations can introduce irrelevant information which can even be exaggerated after view combinations. Feature selection should therefore be incorporated in the process of multi-view learning. In this paper, we explore tensor product to bring different views together in a joint space, and present a dual method of tensor-based multi-view feature selection (dual-Tmfs) based on the idea of support vector machine recursive feature elimination. Experiments conducted on datasets derived from neurological disorder demonstrate the features selected by our proposed method yield better classification performance and are relevant to disease diagnosis. PMID:25937823

  8. The optimal hormonal replacement modality selection for multiple organ procurement from brain-dead organ donors.

    Science.gov (United States)

    Mi, Zhibao; Novitzky, Dimitri; Collins, Joseph F; Cooper, David Kc

    2015-01-01

    The management of brain-dead organ donors is complex. The use of inotropic agents and replacement of depleted hormones (hormonal replacement therapy) is crucial for successful multiple organ procurement, yet the optimal hormonal replacement has not been identified, and the statistical adjustment to determine the best selection is not trivial. Traditional pair-wise comparisons between every pair of treatments, and multiple comparisons to all (MCA), are statistically conservative. Hsu's multiple comparisons with the best (MCB) - adapted from the Dunnett's multiple comparisons with control (MCC) - has been used for selecting the best treatment based on continuous variables. We selected the best hormonal replacement modality for successful multiple organ procurement using a two-step approach. First, we estimated the predicted margins by constructing generalized linear models (GLM) or generalized linear mixed models (GLMM), and then we applied the multiple comparison methods to identify the best hormonal replacement modality given that the testing of hormonal replacement modalities is independent. Based on 10-year data from the United Network for Organ Sharing (UNOS), among 16 hormonal replacement modalities, and using the 95% simultaneous confidence intervals, we found that the combination of thyroid hormone, a corticosteroid, antidiuretic hormone, and insulin was the best modality for multiple organ procurement for transplantation.

  9. Down-regulation of selected Blood-brain Barrier Specific Genes from Capillaries to Bovine In Vitro Models

    DEFF Research Database (Denmark)

    Goldeman, Charlotte; Saaby, Lasse; Brodin, Birger

    Cultures of primary bovine brain endothelial cells (BECs) grown, often together with astrocytes, on permeable supports in two-compartment culture systems are commonly used as an in vitro model of the blood-brain barrier (BBB). While trans-endothelial electrical resistance, restriction...... the in vivo gene expression of brain capillary endothelial cells. Primary bovine endothelial cells and rat astrocytes were cultured in different culture configurations and the mRNA expression of selected genes (vWF, Glut-1, P-gp, claudin-1,-5, occludin, JAM-1, LAT-1, SLC16A1, MRP-1,-4, BCRP, ZO-1, AP, TPA...

  10. Threshold selection for classification of MR brain images by clustering method

    Energy Technology Data Exchange (ETDEWEB)

    Moldovanu, Simona [Faculty of Sciences and Environment, Department of Chemistry, Physics and Environment, Dunărea de Jos University of Galaţi, 47 Domnească St., 800008, Romania, Phone: +40 236 460 780 (Romania); Dumitru Moţoc High School, 15 Milcov St., 800509, Galaţi (Romania); Obreja, Cristian; Moraru, Luminita, E-mail: luminita.moraru@ugal.ro [Faculty of Sciences and Environment, Department of Chemistry, Physics and Environment, Dunărea de Jos University of Galaţi, 47 Domnească St., 800008, Romania, Phone: +40 236 460 780 (Romania)

    2015-12-07

    Given a grey-intensity image, our method detects the optimal threshold for a suitable binarization of MR brain images. In MR brain image processing, the grey levels of pixels belonging to the object are not substantially different from the grey levels belonging to the background. Threshold optimization is an effective tool to separate objects from the background and further, in classification applications. This paper gives a detailed investigation on the selection of thresholds. Our method does not use the well-known method for binarization. Instead, we perform a simple threshold optimization which, in turn, will allow the best classification of the analyzed images into healthy and multiple sclerosis disease. The dissimilarity (or the distance between classes) has been established using the clustering method based on dendrograms. We tested our method using two classes of images: the first consists of 20 T2-weighted and 20 proton density PD-weighted scans from two healthy subjects and from two patients with multiple sclerosis. For each image and for each threshold, the number of the white pixels (or the area of white objects in binary image) has been determined. These pixel numbers represent the objects in clustering operation. The following optimum threshold values are obtained, T = 80 for PD images and T = 30 for T2w images. Each mentioned threshold separate clearly the clusters that belonging of the studied groups, healthy patient and multiple sclerosis disease.

  11. Application of tripolar concentric electrodes and prefeature selection algorithm for brain-computer interface.

    Science.gov (United States)

    Besio, Walter G; Cao, Hongbao; Zhou, Peng

    2008-04-01

    For persons with severe disabilities, a brain-computer interface (BCI) may be a viable means of communication. Lapalacian electroencephalogram (EEG) has been shown to improve classification in EEG recognition. In this work, the effectiveness of signals from tripolar concentric electrodes and disc electrodes were compared for use as a BCI. Two sets of left/right hand motor imagery EEG signals were acquired. An autoregressive (AR) model was developed for feature extraction with a Mahalanobis distance based linear classifier for classification. An exhaust selection algorithm was employed to analyze three factors before feature extraction. The factors analyzed were 1) length of data in each trial to be used, 2) start position of data, and 3) the order of the AR model. The results showed that tripolar concentric electrodes generated significantly higher classification accuracy than disc electrodes.

  12. Bilingualism trains specific brain circuits involved in flexible rule selection and application.

    Science.gov (United States)

    Stocco, Andrea; Prat, Chantel S

    2014-10-01

    Bilingual individuals have been shown to outperform monolinguals on a variety of tasks that measure non-linguistic executive functioning, suggesting that some facets of the bilingual experience give rise to generalized improvements in cognitive performance. The current study investigated the hypothesis that such advantage in executive functioning arises from the need to flexibly select and apply rules when speaking multiple languages. Such flexible behavior may strengthen the functioning of the fronto-striatal loops that direct signals to the prefrontal cortex. To test this hypothesis, we compared behavioral and brain data from proficient bilinguals and monolinguals who performed a Rapid Instructed Task Learning paradigm, which requires behaving according to ever-changing rules. Consistent with our hypothesis, bilinguals were faster than monolinguals when executing novel rules, and this improvement was associated with greater modulation of activity in the basal ganglia. The implications of these findings for language and executive function research are discussed herein. Published by Elsevier Inc.

  13. Acoustic Noise Alters Selective Attention Processes as Indicated by Direct Current (DC Brain Potential Changes

    Directory of Open Access Journals (Sweden)

    Karin Trimmel

    2014-09-01

    Full Text Available Acoustic environmental noise, even of low to moderate intensity, is known to adversely affect information processing in animals and humans via attention mechanisms. In particular, facilitation and inhibition of information processing are basic functions of selective attention. Such mechanisms can be investigated by analyzing brain potentials under conditions of externally directed attention (intake of environmental information versus internally directed attention (rejection of environmental stimuli and focusing on memory/planning processes. This study investigated brain direct current (DC potential shifts—which are discussed to represent different states of cortical activation—of tasks that require intake and rejection of environmental information under noise. It was hypothesized that without background noise rejection tasks would show more positive DC potential changes compared to intake tasks and that under noise both kinds of tasks would show positive DC shifts as an expression of cortical inhibition caused by noise. DC potential shifts during intake and rejection tasks were analyzed at 16 standard locations in 45 persons during irrelevant speech or white noise vs. control condition. Without noise, rejection tasks were associated with more positive DC potential changes compared to intake tasks. During background noise, however, this difference disappeared and both kinds of tasks led to positive DC shifts. Results suggest—besides some limitations—that noise modulates selective attention mechanisms by switching to an environmental information processing and noise rejection mode, which could represent a suggested “attention shift”. Implications for fMRI studies as well as for public health in learning and performance environments including susceptible persons are discussed.

  14. Acoustic noise alters selective attention processes as indicated by direct current (DC) brain potential changes.

    Science.gov (United States)

    Trimmel, Karin; Schätzer, Julia; Trimmel, Michael

    2014-09-26

    Acoustic environmental noise, even of low to moderate intensity, is known to adversely affect information processing in animals and humans via attention mechanisms. In particular, facilitation and inhibition of information processing are basic functions of selective attention. Such mechanisms can be investigated by analyzing brain potentials under conditions of externally directed attention (intake of environmental information) versus internally directed attention (rejection of environmental stimuli and focusing on memory/planning processes). This study investigated brain direct current (DC) potential shifts-which are discussed to represent different states of cortical activation-of tasks that require intake and rejection of environmental information under noise. It was hypothesized that without background noise rejection tasks would show more positive DC potential changes compared to intake tasks and that under noise both kinds of tasks would show positive DC shifts as an expression of cortical inhibition caused by noise. DC potential shifts during intake and rejection tasks were analyzed at 16 standard locations in 45 persons during irrelevant speech or white noise vs. control condition. Without noise, rejection tasks were associated with more positive DC potential changes compared to intake tasks. During background noise, however, this difference disappeared and both kinds of tasks led to positive DC shifts. Results suggest-besides some limitations-that noise modulates selective attention mechanisms by switching to an environmental information processing and noise rejection mode, which could represent a suggested "attention shift". Implications for fMRI studies as well as for public health in learning and performance environments including susceptible persons are discussed.

  15. Prenatal nicotinic exposure suppresses fetal adrenal steroidogenesis via steroidogenic factor 1 (SF-1) deacetylation

    Energy Technology Data Exchange (ETDEWEB)

    Yan, You-e [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan (China); Liu, Lian [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan (China); Department of Pharmacology, Medical School of Yangtze University, Jingzhou 434000 (China); Wang, Jian-fei; Liu, Fang; Li, Xiao-hai; Qin, Hai-quan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China)

    2014-06-15

    This study aimed to investigate the suppressive effect of nicotine on fetal adrenal steroidogenesis and to explore the potential role of epigenetic modification of steroidogenic factor-1 (SF-1) transcriptional activity in this process. Nicotine was intragastrically administered to pregnant rats and NCI-H295A cells were treated with nicotine or trichostatin A (TSA). The pathomorphology of fetal adrenals, steroid hormone levels, the expression of SF-1 and its target genes, and histone deacetylase (HDAC) mRNA were analyzed. Histone modification and DNA methylation of the SF-1 promoter region were assessed using chromatin immunoprecipitation (ChIP) and bisulfite sequencing PCR. The interaction between SF1 and its target genes was observed. Prenatal nicotinic exposure decreased fetal body weight, increased the IUGR rate and caused detrimental changes in fetal adrenal. In addition, the levels of corticosterone, the expression of SF-1 and its target genes were decreased while HDAC2 expression was enhanced. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels while there was no effect on the methylation frequency on the SF-1 promoter region. Furthermore, in nicotine-treated NCI-H295A cells, lower levels of steroidogenic synthesis, lower expression of SF-1 and its target genes were observed while the expression of HDACs was enhanced. The interaction between SF1 and StAR decreased with nicotine treatment. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels, and addition of TSA reversed the inhibition of nicotine-mediated SF-1 and its partial target genes. Thus, nicotine-mediated reduction of SF-1 expression resulted in an inhibitory effect on the expression of its target genes and steroid production via histone deacetylation. - Highlights: • Prenatal nicotine-exposed suppresses fetal adrenal steroidogenesis. • Nicotine-supressed fetal adrenal steroidogenesis is related to SF-1 deacetylation. • Prenatal nicotinic exposure decreased

  16. Prenatal nicotinic exposure suppresses fetal adrenal steroidogenesis via steroidogenic factor 1 (SF-1) deacetylation

    International Nuclear Information System (INIS)

    Yan, You-e; Liu, Lian; Wang, Jian-fei; Liu, Fang; Li, Xiao-hai; Qin, Hai-quan; Wang, Hui

    2014-01-01

    This study aimed to investigate the suppressive effect of nicotine on fetal adrenal steroidogenesis and to explore the potential role of epigenetic modification of steroidogenic factor-1 (SF-1) transcriptional activity in this process. Nicotine was intragastrically administered to pregnant rats and NCI-H295A cells were treated with nicotine or trichostatin A (TSA). The pathomorphology of fetal adrenals, steroid hormone levels, the expression of SF-1 and its target genes, and histone deacetylase (HDAC) mRNA were analyzed. Histone modification and DNA methylation of the SF-1 promoter region were assessed using chromatin immunoprecipitation (ChIP) and bisulfite sequencing PCR. The interaction between SF1 and its target genes was observed. Prenatal nicotinic exposure decreased fetal body weight, increased the IUGR rate and caused detrimental changes in fetal adrenal. In addition, the levels of corticosterone, the expression of SF-1 and its target genes were decreased while HDAC2 expression was enhanced. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels while there was no effect on the methylation frequency on the SF-1 promoter region. Furthermore, in nicotine-treated NCI-H295A cells, lower levels of steroidogenic synthesis, lower expression of SF-1 and its target genes were observed while the expression of HDACs was enhanced. The interaction between SF1 and StAR decreased with nicotine treatment. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels, and addition of TSA reversed the inhibition of nicotine-mediated SF-1 and its partial target genes. Thus, nicotine-mediated reduction of SF-1 expression resulted in an inhibitory effect on the expression of its target genes and steroid production via histone deacetylation. - Highlights: • Prenatal nicotine-exposed suppresses fetal adrenal steroidogenesis. • Nicotine-supressed fetal adrenal steroidogenesis is related to SF-1 deacetylation. • Prenatal nicotinic exposure decreased

  17. An event-related brain potential study of visual selective attention to conjunctions of color and shape.

    Science.gov (United States)

    Smid, H G; Jakob, A; Heinze, H J

    1999-03-01

    What cognitive processes underlie event-related brain potential (ERP) effects related to visual multidimensional selective attention and how are these processes organized? We recorded ERPs when participants attended to one conjunction of color, global shape and local shape and ignored other conjunctions of these attributes in three discriminability conditions. Attending to color and shape produced three ERP effects: frontal selection positivity (FSP), central negativity (N2b), and posterior selection negativity (SN). The results suggested that the processes underlying SN and N2b perform independent within-dimension selections, whereas the process underlying the FSP performs hierarchical between-dimension selections. At posterior electrodes, manipulation of discriminability changed the ERPs to the relevant but not to the irrelevant stimuli, suggesting that the SN does not concern the selection process itself but rather a cognitive process initiated after selection is finished. Other findings suggested that selection of multiple visual attributes occurs in parallel.

  18. Label fusion based brain MR image segmentation via a latent selective model

    Science.gov (United States)

    Liu, Gang; Guo, Xiantang; Zhu, Kai; Liao, Hengxu

    2018-04-01

    Multi-atlas segmentation is an effective approach and increasingly popular for automatically labeling objects of interest in medical images. Recently, segmentation methods based on generative models and patch-based techniques have become the two principal branches of label fusion. However, these generative models and patch-based techniques are only loosely related, and the requirement for higher accuracy, faster segmentation, and robustness is always a great challenge. In this paper, we propose novel algorithm that combines the two branches using global weighted fusion strategy based on a patch latent selective model to perform segmentation of specific anatomical structures for human brain magnetic resonance (MR) images. In establishing this probabilistic model of label fusion between the target patch and patch dictionary, we explored the Kronecker delta function in the label prior, which is more suitable than other models, and designed a latent selective model as a membership prior to determine from which training patch the intensity and label of the target patch are generated at each spatial location. Because the image background is an equally important factor for segmentation, it is analyzed in label fusion procedure and we regard it as an isolated label to keep the same privilege between the background and the regions of interest. During label fusion with the global weighted fusion scheme, we use Bayesian inference and expectation maximization algorithm to estimate the labels of the target scan to produce the segmentation map. Experimental results indicate that the proposed algorithm is more accurate and robust than the other segmentation methods.

  19. Nonspatial intermodal selective attention is mediated by sensory brain brain areas: Evidence from event-related potential.

    NARCIS (Netherlands)

    Talsma, D.; Kok, A.

    2001-01-01

    Focuses on the question of whether inter-and intramodal forms of attention are reflected in activation of the same or different brain areas. ERPs were recorded while Ss (aged 18-41 yrs) were presented a random sequence of visual and auditory stimuli. They were instructed to attend to nonspatial

  20. Effects of concanavalin A on the progesterone production by bovine steroidogenic luteal cells in vitro.

    Science.gov (United States)

    Destro, F C; Martin, I; Landim-Alvarenga, Fdc; Ferreira, Jcp; Pate, J L

    2016-10-01

    The aim of this study was to evaluate the effects of concanavalin A (CONA) on the progesterone (P4) production by bovine steroidogenic luteal cells (LCs) in vitro. Luteal cells were collected during the mid-luteal stage (at 10-12 days following ovulation) and processed in the laboratory. Luteal cells were grown for 7 days in a humid atmosphere with 5% CO2 , with or without 10% foetal bovine serum, and were subjected to the following treatments: control: no treatment; CONA (10 μg/ml); LH (100 μg/ml); CONA + LH; LH (100 μg/ml) + prostaglandin F2α (PGF2α) (10 ng/ml); CONA + LH + PGF2α. Samples of the culture media were collected on days 1 (D1) and 7 (D7) for P4 quantification. The cells were counted on D7 of culture. Differences between treatments were considered statistically significant at p < .05. Culture in the presence of CONA decreased the P4-secreting capacity of LCs on D7 of culture, particularly in the absence of serum. The cell numbers did not change between treatments. © 2016 Blackwell Verlag GmbH.

  1. Inhibitory effect of tributyltin on expression of steroidogenic enzymes in mouse testis.

    Science.gov (United States)

    Kim, Suel-Kee; Kim, Jong-Hoon; Han, Jung Ho; Yoon, Yong-Dal

    2008-01-01

    Tributyltin (TBT) is known to disrupt the development of reproductive organs, thereby reducing fertility. The aim of this study was to evaluate the acute toxicity of TBT on the testicular development and steroid hormone production. Immature (3-week-old) male mice were given a single administration of 25, 50, or 100 mg/kg of TBT by oral gavage. Lumen formation in seminiferous tubule was remarkably delayed, and the number of apoptotic germ cells found inside the tubules was increased in the TBT-exposed animals, whereas no apoptotic signal was observed in interstitial Leydig cells. Reduced serum testosterone concentration and down-regulated expressions of the mRNAs for cholesterol side-chain cleavage enzyme (P450scc), 17alpha -hydroxylase/C(17-20) lyase (P450(17alpha)), 3beta -hydroxysteroid-dehydrogenase (3beta -HSD), and 17beta -hydroxysteroid-dehydrogenase (17beta -HSD) were also observed after TBT exposure. Altogether, these findings demonstrate that exposure to TBT is associated with induced apoptosis of testicular germ cells and inhibition of steroidogenesis by reduction in the expression of steroidogenic enzymes in interstitial Leydig cells. These adverse effects of TBT would cause serious defects in testicular development and function.

  2. Cerebellins are differentially expressed in selective subsets of neurons throughout the brain.

    Science.gov (United States)

    Seigneur, Erica; Südhof, Thomas C

    2017-10-15

    Cerebellins are secreted hexameric proteins that form tripartite complexes with the presynaptic cell-adhesion molecules neurexins or 'deleted-in-colorectal-cancer', and the postsynaptic glutamate-receptor-related proteins GluD1 and GluD2. These tripartite complexes are thought to regulate synapses. However, cerebellins are expressed in multiple isoforms whose relative distributions and overall functions are not understood. Three of the four cerebellins, Cbln1, Cbln2, and Cbln4, autonomously assemble into homohexamers, whereas the Cbln3 requires Cbln1 for assembly and secretion. Here, we show that Cbln1, Cbln2, and Cbln4 are abundantly expressed in nearly all brain regions, but exhibit strikingly different expression patterns and developmental dynamics. Using newly generated knockin reporter mice for Cbln2 and Cbln4, we find that Cbln2 and Cbln4 are not universally expressed in all neurons, but only in specific subsets of neurons. For example, Cbln2 and Cbln4 are broadly expressed in largely non-overlapping subpopulations of excitatory cortical neurons, but only sparse expression was observed in excitatory hippocampal neurons of the CA1- or CA3-region. Similarly, Cbln2 and Cbln4 are selectively expressed, respectively, in inhibitory interneurons and excitatory mitral projection neurons of the main olfactory bulb; here, these two classes of neurons form dendrodendritic reciprocal synapses with each other. A few brain regions, such as the nucleus of the lateral olfactory tract, exhibit astoundingly high Cbln2 expression levels. Viewed together, our data show that cerebellins are abundantly expressed in relatively small subsets of neurons, suggesting specific roles restricted to subsets of synapses. © 2017 Wiley Periodicals, Inc.

  3. An event-related brain potential study of visual selective attention to conjunctions of color and shape

    NARCIS (Netherlands)

    Smid, HGOM; Jakob, A; Heinze, HJ

    What cognitive processes underlie event-related brain potential (ERP) effects related to visual multidimensional selective attention and how are these processes organized? We recorded ERPs when participants attended to one conjunction of color, global shape and local shape and ignored other

  4. Linguistic processing in visual and modality-nonspecific brain areas: PET recordings during selective attention.

    Science.gov (United States)

    Vorobyev, Victor A; Alho, Kimmo; Medvedev, Svyatoslav V; Pakhomov, Sergey V; Roudas, Marina S; Rutkovskaya, Julia M; Tervaniemi, Mari; Van Zuijen, Titia L; Näätänen, Risto

    2004-07-01

    Positron emission tomography (PET) was used to investigate the neural basis of selective processing of linguistic material during concurrent presentation of multiple stimulus streams ("cocktail-party effect"). Fifteen healthy right-handed adult males were to attend to one of three simultaneously presented messages: one presented visually, one to the left ear, and one to the right ear. During the control condition, subjects attended to visually presented consonant letter strings and ignored auditory messages. This paper reports the modality-nonspecific language processing and visual word-form processing, whereas the auditory attention effects have been reported elsewhere [Cogn. Brain Res. 17 (2003) 201]. The left-hemisphere areas activated by both the selective processing of text and speech were as follows: the inferior prefrontal (Brodmann's area, BA 45, 47), anterior temporal (BA 38), posterior insular (BA 13), inferior (BA 20) and middle temporal (BA 21), occipital (BA 18/30) cortices, the caudate nucleus, and the amygdala. In addition, bilateral activations were observed in the medial occipito-temporal cortex and the cerebellum. Decreases of activation during both text and speech processing were found in the parietal (BA 7, 40), frontal (BA 6, 8, 44) and occipito-temporal (BA 37) regions of the right hemisphere. Furthermore, the present data suggest that the left occipito-temporal cortex (BA 18, 20, 37, 21) can be subdivided into three functionally distinct regions in the posterior-anterior direction on the basis of their activation during attentive processing of sublexical orthography, visual word form, and supramodal higher-level aspects of language.

  5. Collaborative filtering for brain-computer interaction using transfer learning and active class selection.

    Directory of Open Access Journals (Sweden)

    Dongrui Wu

    Full Text Available Brain-computer interaction (BCI and physiological computing are terms that refer to using processed neural or physiological signals to influence human interaction with computers, environment, and each other. A major challenge in developing these systems arises from the large individual differences typically seen in the neural/physiological responses. As a result, many researchers use individually-trained recognition algorithms to process this data. In order to minimize time, cost, and barriers to use, there is a need to minimize the amount of individual training data required, or equivalently, to increase the recognition accuracy without increasing the number of user-specific training samples. One promising method for achieving this is collaborative filtering, which combines training data from the individual subject with additional training data from other, similar subjects. This paper describes a successful application of a collaborative filtering approach intended for a BCI system. This approach is based on transfer learning (TL, active class selection (ACS, and a mean squared difference user-similarity heuristic. The resulting BCI system uses neural and physiological signals for automatic task difficulty recognition. TL improves the learning performance by combining a small number of user-specific training samples with a large number of auxiliary training samples from other similar subjects. ACS optimally selects the classes to generate user-specific training samples. Experimental results on 18 subjects, using both k nearest neighbors and support vector machine classifiers, demonstrate that the proposed approach can significantly reduce the number of user-specific training data samples. This collaborative filtering approach will also be generalizable to handling individual differences in many other applications that involve human neural or physiological data, such as affective computing.

  6. Collaborative filtering for brain-computer interaction using transfer learning and active class selection.

    Science.gov (United States)

    Wu, Dongrui; Lance, Brent J; Parsons, Thomas D

    2013-01-01

    Brain-computer interaction (BCI) and physiological computing are terms that refer to using processed neural or physiological signals to influence human interaction with computers, environment, and each other. A major challenge in developing these systems arises from the large individual differences typically seen in the neural/physiological responses. As a result, many researchers use individually-trained recognition algorithms to process this data. In order to minimize time, cost, and barriers to use, there is a need to minimize the amount of individual training data required, or equivalently, to increase the recognition accuracy without increasing the number of user-specific training samples. One promising method for achieving this is collaborative filtering, which combines training data from the individual subject with additional training data from other, similar subjects. This paper describes a successful application of a collaborative filtering approach intended for a BCI system. This approach is based on transfer learning (TL), active class selection (ACS), and a mean squared difference user-similarity heuristic. The resulting BCI system uses neural and physiological signals for automatic task difficulty recognition. TL improves the learning performance by combining a small number of user-specific training samples with a large number of auxiliary training samples from other similar subjects. ACS optimally selects the classes to generate user-specific training samples. Experimental results on 18 subjects, using both k nearest neighbors and support vector machine classifiers, demonstrate that the proposed approach can significantly reduce the number of user-specific training data samples. This collaborative filtering approach will also be generalizable to handling individual differences in many other applications that involve human neural or physiological data, such as affective computing.

  7. Feature Selection and Blind Source Separation in an EEG-Based Brain-Computer Interface

    Directory of Open Access Journals (Sweden)

    Michael H. Thaut

    2005-11-01

    Full Text Available Most EEG-based BCI systems make use of well-studied patterns of brain activity. However, those systems involve tasks that indirectly map to simple binary commands such as “yes” or “no” or require many weeks of biofeedback training. We hypothesized that signal processing and machine learning methods can be used to discriminate EEG in a direct “yes”/“no” BCI from a single session. Blind source separation (BSS and spectral transformations of the EEG produced a 180-dimensional feature space. We used a modified genetic algorithm (GA wrapped around a support vector machine (SVM classifier to search the space of feature subsets. The GA-based search found feature subsets that outperform full feature sets and random feature subsets. Also, BSS transformations of the EEG outperformed the original time series, particularly in conjunction with a subset search of both spaces. The results suggest that BSS and feature selection can be used to improve the performance of even a “direct,” single-session BCI.

  8. The spiritual brain: selective cortical lesions modulate human self-transcendence.

    Science.gov (United States)

    Urgesi, Cosimo; Aglioti, Salvatore M; Skrap, Miran; Fabbro, Franco

    2010-02-11

    The predisposition of human beings toward spiritual feeling, thinking, and behaviors is measured by a supposedly stable personality trait called self-transcendence. Although a few neuroimaging studies suggest that neural activation of a large fronto-parieto-temporal network may underpin a variety of spiritual experiences, information on the causative link between such a network and spirituality is lacking. Combining pre- and post-neurosurgery personality assessment with advanced brain-lesion mapping techniques, we found that selective damage to left and right inferior posterior parietal regions induced a specific increase of self-transcendence. Therefore, modifications of neural activity in temporoparietal areas may induce unusually fast modulations of a stable personality trait related to transcendental self-referential awareness. These results hint at the active, crucial role of left and right parietal systems in determining self-transcendence and cast new light on the neurobiological bases of altered spiritual and religious attitudes and behaviors in neurological and mental disorders. Copyright 2010 Elsevier Inc. All rights reserved.

  9. Effects of alkylating agents on dopamine D(3) receptors in rat brain: selective protection by dopamine.

    Science.gov (United States)

    Zhang, K; Weiss, N T; Tarazi, F I; Kula, N S; Baldessarini, R J

    1999-11-13

    Dopamine D(3) receptors are structurally highly homologous to other D(2)-like dopamine receptors, but differ from them pharmacologically. D(3) receptors are notably resistant to alkylation by 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), which readily alkylates D(2) receptors. We compared EEDQ with N-(p-isothiocyanatophenethyl)spiperone (NIPS), a selective D(2)-like receptor alkylating agent, for effects on D(3) and D(2) receptors in rat brain using autoradiographic analysis. Neither agent occluded D(3) receptors in vivo at doses that produced substantial blockade of D(2) receptors, even after catecholamine-depleting pretreatments. In vitro, however, D(3) receptors were readily alkylated by both NIPS (IC(50)=40 nM) and EEDQ (IC(50)=12 microM). These effects on D(3) sites were blocked by nM concentrations of dopamine, whereas microM concentrations were required to protect D(2) receptors from the alkylating agents. The findings are consistent with the view that alkylation of D(3) receptors in vivo is prevented by its high affinity for even minor concentrations of endogenous dopamine.

  10. Natural selection in avian protein-coding genes expressed in brain.

    Science.gov (United States)

    Axelsson, Erik; Hultin-Rosenberg, Lina; Brandström, Mikael; Zwahlén, Martin; Clayton, David F; Ellegren, Hans

    2008-06-01

    The evolution of birds from theropod dinosaurs took place approximately 150 million years ago, and was associated with a number of specific adaptations that are still evident among extant birds, including feathers, song and extravagant secondary sexual characteristics. Knowledge about the molecular evolutionary background to such adaptations is lacking. Here, we analyse the evolution of > 5000 protein-coding gene sequences expressed in zebra finch brain by comparison to orthologous sequences in chicken. Mean d(N)/d(S) is 0.085 and genes with their maximal expression in the eye and central nervous system have the lowest mean d(N)/d(S) value, while those expressed in digestive and reproductive tissues exhibit the highest. We find that fast-evolving genes (those which have higher than expected rate of nonsynonymous substitution, indicative of adaptive evolution) are enriched for biological functions such as fertilization, muscle contraction, defence response, response to stress, wounding and endogenous stimulus, and cell death. After alignment to mammalian orthologues, we identify a catalogue of 228 genes that show a significantly higher rate of protein evolution in the two bird lineages than in mammals. These accelerated bird genes, representing candidates for avian-specific adaptations, include genes implicated in vocal learning and other cognitive processes. Moreover, colouration genes evolve faster in birds than in mammals, which may have been driven by sexual selection for extravagant plumage characteristics.

  11. Achieving a hybrid brain-computer interface with tactile selective attention and motor imagery

    Science.gov (United States)

    Ahn, Sangtae; Ahn, Minkyu; Cho, Hohyun; Jun, Sung Chan

    2014-12-01

    Objective. We propose a new hybrid brain-computer interface (BCI) system that integrates two different EEG tasks: tactile selective attention (TSA) using a vibro-tactile stimulator on the left/right finger and motor imagery (MI) of left/right hand movement. Event-related desynchronization (ERD) from the MI task and steady-state somatosensory evoked potential (SSSEP) from the TSA task are retrieved and combined into two hybrid senses. Approach. One hybrid approach is to measure two tasks simultaneously; the features of each task are combined for testing. Another hybrid approach is to measure two tasks consecutively (TSA first and MI next) using only MI features. For comparison with the hybrid approaches, the TSA and MI tasks are measured independently. Main results. Using a total of 16 subject datasets, we analyzed the BCI classification performance for MI, TSA and two hybrid approaches in a comparative manner; we found that the consecutive hybrid approach outperformed the others, yielding about a 10% improvement in classification accuracy relative to MI alone. It is understood that TSA may play a crucial role as a prestimulus in that it helps to generate earlier ERD prior to MI and thus sustains ERD longer and to a stronger degree; this ERD may give more discriminative information than ERD in MI alone. Significance. Overall, our proposed consecutive hybrid approach is very promising for the development of advanced BCI systems.

  12. Local-learning-based neuron selection for grasping gesture prediction in motor brain machine interfaces

    Science.gov (United States)

    Xu, Kai; Wang, Yiwen; Wang, Yueming; Wang, Fang; Hao, Yaoyao; Zhang, Shaomin; Zhang, Qiaosheng; Chen, Weidong; Zheng, Xiaoxiang

    2013-04-01

    Objective. The high-dimensional neural recordings bring computational challenges to movement decoding in motor brain machine interfaces (mBMI), especially for portable applications. However, not all recorded neural activities relate to the execution of a certain movement task. This paper proposes to use a local-learning-based method to perform neuron selection for the gesture prediction in a reaching and grasping task. Approach. Nonlinear neural activities are decomposed into a set of linear ones in a weighted feature space. A margin is defined to measure the distance between inter-class and intra-class neural patterns. The weights, reflecting the importance of neurons, are obtained by minimizing a margin-based exponential error function. To find the most dominant neurons in the task, 1-norm regularization is introduced to the objective function for sparse weights, where near-zero weights indicate irrelevant neurons. Main results. The signals of only 10 neurons out of 70 selected by the proposed method could achieve over 95% of the full recording's decoding accuracy of gesture predictions, no matter which different decoding methods are used (support vector machine and K-nearest neighbor). The temporal activities of the selected neurons show visually distinguishable patterns associated with various hand states. Compared with other algorithms, the proposed method can better eliminate the irrelevant neurons with near-zero weights and provides the important neuron subset with the best decoding performance in statistics. The weights of important neurons converge usually within 10-20 iterations. In addition, we study the temporal and spatial variation of neuron importance along a period of one and a half months in the same task. A high decoding performance can be maintained by updating the neuron subset. Significance. The proposed algorithm effectively ascertains the neuronal importance without assuming any coding model and provides a high performance with different

  13. Reproductive gonadal steroidogenic activity in the fishing cat (Prionailurus viverrinus) assessed by fecal steroid analyses.

    Science.gov (United States)

    Santymire, Rachel M; Brown, Janine L; Stewart, Rosemary A; Santymire, Robb C; Wildt, David E; Howard, JoGayle

    2011-10-01

    Non-invasive fecal steroid analyses were used to characterize gonadal activity in the fishing cat (Prionailurus viverrinus). Estrogen, progestagen and androgen metabolites were quantified in fecal samples collected for 12 months from four males and 10 females housed at seven North American zoological institutions. Male reproductive hormone concentrations did not vary (P>0.05) among season, and estrogen cycles were observed year-round in females and averaged (±SEM) 19.9±1.0 days. Mean peak estrogen concentration during estrus (460.0±72.6ng/g feces) was five-fold higher than baseline (87.3±14.0ng/g feces). Five of seven females (71.4%) housed alone or with another female demonstrated spontaneous luteal activity (apparent ovulation without copulation), with mean progestagen concentration (20.3±4.7μg/g feces), increasing nearly five-fold above baseline (4.1±0.8μg/g feces). The non-pregnant luteal phase averaged 32.9±2.5 days (n=13). One female delivered kittens 70 days after natural mating with fecal progestagen concentrations averaging 51.2±5.2μg/g feces. Two additional females were administered exogenous gonadotropins (150IU eCG; 100IU hCG), which caused hyper-elevated concentrations of fecal estrogen and progestagen (plus ovulation). Results indicate that: (1) male and female fishing cats managed in North American zoos are reproductively active year round; (2) 71.4% of females experienced spontaneous ovulation; and (3) females are responsive to exogenous gonadotropins for ovulation induction, but a regimen that produces a normative ovarian steroidogenic response needs to be identified. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Immunohistochemical evaluation of proliferation, apoptosis and steroidogenic enzymes in the ovary of rats with polycystic ovary

    Directory of Open Access Journals (Sweden)

    Leonardo Augusto Lombardi

    2014-07-01

    Full Text Available Objective: to evaluate the immunohistochemical expression of proliferative, apoptotic and steroidogenic enzyme markers in the ovaries of rats with polycystic ovary syndrome (PCOS. Methods: twenty rats were divided into two groups: GCtrl - estrous phase, and PCOS - with polycystic ovaries. The GCtrl animals were subjected to a lighting period from 7 am to 7 pm, while the animals with PCOS group remained with continuous lighting for 60 days. Subsequently, the animals were anesthetized, the ovaries were removed and fixed in 10% formaldehyde, prior to paraffin embedding. Sections were stained using H.E. or subjected to immunohistochemical methods for the detection of Ki-67, cleaved caspase-3, CYP11A1, CYP17A1 and CYP19A1. The results were analyzed using Student's t-test (p < 0,05. Results: morphological results showed evidence of interstitial cells originating from the inner theca cells of degenerating ovarian cysts in PCOS. Immunoexpression of Ki-67 was higher in the granulosa cells in GCtrl, and the theca interna cells in PCOS, while cleaved caspase-3 was higher in granulosa cells of ovarian cysts from PCOS and in the theca interna cells of GCtrl. Immunoreactivity of CYP11A1 in the theca interna, granulosa and interstitial cells was similar between the two groups, while CYP17A1 and CYP19A1 were higher in the granulosa and interstitial cells in the PCOS group. Conclusion: the results indicate that the interstitial cells are derived from the theca interna and that enzymatic changes occur in the theca interna and interstitial cells in ovaries of rats with PCOS, responsible for the high levels of androgens and estradiol.

  15. Gonadal function in males with autoimmune Addison's disease and autoantibodies to steroidogenic enzymes.

    Science.gov (United States)

    Dalla Costa, M; Bonanni, G; Masiero, S; Faggian, D; Chen, S; Furmaniak, J; Rees Smith, B; Perniola, R; Radetti, G; Garelli, S; Chiarelli, S; Albergoni, M P; Plebani, M; Betterle, C

    2014-06-01

    Steroidogenic enzyme autoantibodies (SEAbs) are frequently present and are markers of autoimmune premature ovarian failure (POF) in females with autoimmune Addison's disease (AAD). The prevalence and significance of SEAbs in males with AAD have not yet been defined. We studied the prevalence of SEAbs in a large cohort of males with AAD and assessed the relationship between SEAbs positivity and testicular function. A total of 154 males with AAD (mean age 34 years) were studied. SEAbs included autoantibodies to steroid-producing cells (StCA), detected by immunofluorescence, and steroid 17α-hydroxylase (17α-OHAbs) and side chain cleavage enzyme (SCCAbs) measured by immunoprecipitation assays. Gonadal function was evaluated by measuring follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), sex hormone-binding globulin (SHGB), anti-müllerian hormone (AMH) and inhibin-B (I-B). Twenty-six males, 10 SEAbs((+)) and 16 SEAbs((-)), were followed-up for a mean period of 7·6 years to assess the behaviour of SEAbs and testicular function. SEAbs were found in 24·7% of males with AAD, with the highest frequency in patients with autoimmune polyendocrine syndrome type 1 (APS-1). The levels of reproductive hormones in 30 SEAbs((+)) males were in the normal range according to age and were not significantly different compared to 55 SEAbs((-)) males (P > 0·05). During follow-up, both SEAbs((+)) and SEAbs((-)) patients maintained normal testicular function. SEAbs were found with high frequency in males with AAD; however, they were not associated with testicular failure. This study suggests that the diagnostic value of SEAbs in males with AAD differs compared to females, and this may be related to the immunoprivileged status of the testis. © 2014 British Society for Immunology.

  16. Screening of ovarian steroidogenic pathway in Ciona intestinalis and its modulation after tributyltin exposure

    International Nuclear Information System (INIS)

    Cangialosi, Maria Vittoria; Puccia, Egidio; Mazzola, Antonio; Mansueto, Valentina; Arukwe, Augustine

    2010-01-01

    In this study, we have identified several ovarian steroids in Ciona with high similarity to vertebrate steroids and showed that cholesterol, corticosterone, dehydroepiandrosterone, estrone, estradiol-17β, testosterone, pregnenolone, progesterone, have identical molecular spectra with vertebrate steroids. In addition, we have studied the effects of an endocrine disruptor (tributyltin: TBT) on these sex hormones and their precursors, ovarian morphology, and gene expression of some key enzymes in steroidogenic pathway in the ovary of Ciona. Ovarian specimens were cultured in vitro using different concentrations of TBT (10 -5 , 10 -4 and 10 -3 M). Ethanol was used as solvent control. Gene expression analysis was performed for adrenodoxin (ADREN) and adrenodoxin reductase (ADOX) (mediators of acute steroidogenesis) and 17β-hydroxysteroid dehydrogenase (17β-HSD). These transcripts were detected and measured by quantitative (real-time) polymerase chain reaction (qPCR). Sex steroids and their precursors were identified and quantified by a gas chromatography-mass spectroscopy (GC-MS) method. Exposure of Ciona ovaries to TBT produced modulations (either increased or decreased) of sterols and sex steroid levels, whereas no significant differences in ADREN, ADOX or 17β-HSD mRNA expression patterns were observed. Histological analysis shows that TBT produced several modifications on Ciona ovarian morphology that includes irregular outline of nuclear membrane, less compacted cytoplasm, in addition to test and granulosa cells that were detached from the oocyte membrane. Given that the ascidians represent very simple experimental models for the study of endocrine disruption by environmental contaminants, our findings provide excellent models for multiple identification and quantification of sex steroid and their precursors in biological samples exposed to endocrine-disrupting chemicals and for direct extrapolation of such effects across taxonomic groups and phyla. In addition

  17. Embedding filtering criteria into a wrapper marker selection method for brain tumor classification: an application on metabolic peak area ratios

    International Nuclear Information System (INIS)

    Kounelakis, M G; Zervakis, M E; Giakos, G C; Postma, G J; Buydens, L M C; Kotsiakis, X

    2011-01-01

    The purpose of this study is to identify reliable sets of metabolic markers that provide accurate classification of complex brain tumors and facilitate the process of clinical diagnosis. Several ratios of metabolites are tested alone or in combination with imaging markers. A wrapper feature selection and classification methodology is studied, employing Fisher's criterion for ranking the markers. The set of extracted markers that express statistical significance is further studied in terms of biological behavior with respect to the brain tumor type and grade. The outcome of this study indicates that the proposed method by exploiting the intrinsic properties of data can actually reveal reliable and biologically relevant sets of metabolic markers, which form an important adjunct toward a more accurate type and grade discrimination of complex brain tumors

  18. Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain.

    Science.gov (United States)

    Buckholtz, N S; Zhou, D F; Freedman, D X; Potter, W Z

    1990-04-01

    A dosage regimen of lysergic acid diethylamide (LSD) that reliably produces behavioral tolerance in rats was evaluated for effects on neurotransmitter receptor binding in rat brain using a variety of radioligands selective for amine receptor subtypes. Daily administration of LSD [130 micrograms/kg (0.27 mumol/kg) intraperitoneally (IP)] for 5 days produced a decrease in serotonin2 (5-hydroxytryptamine2, 5-HT2) binding in cortex (measured 24 hours after the last drug administration) but did not affect binding to other receptor systems (5-HT1A, 5-HT1B, beta-adrenergic, alpha 1- or alpha 2-adrenergic, D2-dopaminergic) or to a recognition site for 5-HT uptake. The decrease was evident within 3 days of LSD administration but was not demonstrable after the first LSD dose. Following 5 days of LSD administration the decrease was still present 48 hours, but not 96 hours, after the last administration. The indole hallucinogen psilocybin [1.0 mg/kg (3.5 mumol/kg) for 8 days] also produced a significant decrease in 5HT2 binding, but neither the nonhallucinogenic analog bromo-LSD [1.3 mg/kg (2.4 mumol/kg) for 5 days] nor mescaline [10 mg/kg (40.3 mumol/kg) for 5 or 10 days] affected 5-HT2 binding. These observations suggest that LSD and other indole hallucinogens may act as 5-HT2 agonists at postsynaptic 5-HT2 receptors. Decreased 5-HT2 binding strikingly parallels the development and loss of behavioral tolerance seen with repeated LSD administration, but the decreased binding per se cannot explain the gamut of behavioral tolerance and cross-tolerance phenomena among the indole and phenylethylamine hallucinogens.

  19. Steroidogenic acute regulatory protein (StAR) gene expression construct: Development, nanodelivery and effect on reproduction in air-breathing catfish, Clarias batrachus.

    Science.gov (United States)

    Rathor, Pravesh Kumar; Bhat, Irfan Ahmad; Rather, Mohd Ashraf; Gireesh-Babu, Pathakota; Kumar, Kundan; Purayil, Suresh Babu Padinhate; Sharma, Rupam

    2017-11-01

    Steroidogenic acute regulatory protein (StAR) is responsible for the relocation of cholesterol across mitochondrial membrane in vertebrates and is, therefore, a key factor in regulating the rate and timing of steroidogenesis. In the present study, we developed chitosan nanoparticle (CNP) conjugated StAR gene construct (CNP-pcDNA4-StAR) in a eukaryotic expression vector, pcDNA4/HisMax A. CNPs of 135.4nm diameter, 26.7mV zeta potential and 0.381 polydispersity index were used for conjugation. The loading efficiency (LE) of pcDNA4-StAR construct with CNPs was found to be 86%. After the 24h of intramuscular injection, the CNP-pcDNA4-StAR plasmid could be detected from testis, brain, kidney and muscle tissues of Clarias batrachus. The transcript levels of important reproductive genes viz. cyp11a1, cyp17a1, 3β-hsd, 17β-hsd and cyp19a1 in CNP-pcDNA4-StAR treated group were initially low up to 24h, but significantly increased subsequently up to 120h. In naked pcDNA4-StAR treated group, the mRNA level of 3β-hsd, 17β-hsd and cyp19a1 increased initially up to 24h, while cyp11a1 and cyp17a1 increased up to 48h and then started declining. Similar results were obtained for 11-Ketotestosterone and 17β-estradiol. The results indicate relatively long lasting effects of nano-conjugated construct compared to the construct alone. Furthermore, the histopathology of gonads and liver authenticates its possible role in the gonadal development in fish without any adverse effect. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Selective targeting of brain tumors with gold nanoparticle-induced radiosensitization.

    Directory of Open Access Journals (Sweden)

    Daniel Y Joh

    Full Text Available Successful treatment of brain tumors such as glioblastoma multiforme (GBM is limited in large part by the cumulative dose of Radiation Therapy (RT that can be safely given and the blood-brain barrier (BBB, which limits the delivery of systemic anticancer agents into tumor tissue. Consequently, the overall prognosis remains grim. Herein, we report our pilot studies in cell culture experiments and in an animal model of GBM in which RT is complemented by PEGylated-gold nanoparticles (GNPs. GNPs significantly increased cellular DNA damage inflicted by ionizing radiation in human GBM-derived cell lines and resulted in reduced clonogenic survival (with dose-enhancement ratio of ~1.3. Intriguingly, combined GNP and RT also resulted in markedly increased DNA damage to brain blood vessels. Follow-up in vitro experiments confirmed that the combination of GNP and RT resulted in considerably increased DNA damage in brain-derived endothelial cells. Finally, the combination of GNP and RT increased survival of mice with orthotopic GBM tumors. Prior treatment of mice with brain tumors resulted in increased extravasation and in-tumor deposition of GNP, suggesting that RT-induced BBB disruption can be leveraged to improve the tumor-tissue targeting of GNP and thus further optimize the radiosensitization of brain tumors by GNP. These exciting results together suggest that GNP may be usefully integrated into the RT treatment of brain tumors, with potential benefits resulting from increased tumor cell radiosensitization to preferential targeting of tumor-associated vasculature.

  1. Discovery and characterization of ACT-335827, an orally available, brain penetrant orexin receptor type 1 selective antagonist.

    Science.gov (United States)

    Steiner, Michel A; Gatfield, John; Brisbare-Roch, Catherine; Dietrich, Hendrik; Treiber, Alexander; Jenck, Francois; Boss, Christoph

    2013-06-01

    Stress relief: Orexin neuropeptides regulate arousal and stress processing through orexin receptor type 1 (OXR-1) and 2 (OXR-2) signaling. A selective OXR-1 antagonist, represented by a phenylglycine-amide substituted tetrahydropapaverine derivative (ACT-335827), is described that is orally available, penetrates the brain, and decreases fear, compulsive behaviors and autonomic stress reactions in rats. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Nuclear receptor 5A (NR5A) family regulates 5-aminolevulinic acid synthase 1 (ALAS1) gene expression in steroidogenic cells.

    Science.gov (United States)

    Ju, Yunfeng; Mizutani, Tetsuya; Imamichi, Yoshitaka; Yazawa, Takashi; Matsumura, Takehiro; Kawabe, Shinya; Kanno, Masafumi; Umezawa, Akihiro; Kangawa, Kenji; Miyamoto, Kaoru

    2012-11-01

    5-Aminolevulinic acid synthase 1 (ALAS1) is a rate-limiting enzyme for heme biosynthesis in mammals. Heme is essential for the catalytic activities of P450 enzymes including steroid metabolic enzymes. Nuclear receptor 5A (NR5A) family proteins, steroidogenic factor-1 (SF-1), and liver receptor homolog-1 (LRH-1) play pivotal roles in regulation of steroidogenic enzymes. Recently, we showed that expression of SF-1/LRH-1 induces differentiation of mesenchymal stem cells into steroidogenic cells. In this study, genome-wide analysis revealed that ALAS1 was a novel SF-1-target gene in differentiated mesenchymal stem cells. Chromatin immunoprecipitation and reporter assays revealed that SF-1/LRH-1 up-regulated ALAS1 gene transcription in steroidogenic cells via binding to a 3.5-kb upstream region of ALAS1. The ALAS1 gene was up-regulated by overexpression of SF-1/LRH-1 in steroidogenic cells and down-regulated by knockdown of SF-1 in these cells. Peroxisome proliferator-activated receptor-γ coactivator-1α, a coactivator of nuclear receptors, also strongly coactivated expression of NR5A-target genes. Reporter analysis revealed that peroxisome proliferator-activated receptor-γ coactivator-1α strongly augmented ALAS1 gene transcription caused by SF-1 binding to the 3.5-kb upstream region. Finally knockdown of ALAS1 resulted in reduced progesterone production by steroidogenic cells. These results indicate that ALAS1 is a novel NR5A-target gene and participates in steroid hormone production.

  3. An HPLC tracing of the enhancer regulation in selected discrete brain areas of food-deprived rats.

    Science.gov (United States)

    Miklya, I; Knoll, B; Knoll, J

    2003-05-09

    The recent discovery of the enhancer regulation in the mammalian brain brought a different perspective to the brain-organized realization of goal-oriented behavior, which is the quintessence of plastic behavioral descriptions such as drive or motivation. According to this new approach, 'drive' means that special endogenous enhancer substances enhance the impulse-propagation-mediated release of transmitters in a proper population of enhancer-sensitive neurons, and keep these neurons in the state of enhanced excitability until the goal is reached. However, to reach any goal needs the participation of the catecholaminergic machinery, the engine of the brain. We developed a method to detect the specific enhancer effect of synthetic enhancer substances [(-)-deprenyl, (-)-PPAP, (-)-BPAP] by measuring the release of transmitters from freshly isolated selected discrete brain areas (striatum, substantia nigra, tuberculum olfactorium, locus coeruleus, raphe) by the aid of HPLC with electrochemical detection. To test the validity of the working hypothesis that in any form of goal-seeking behavior the catecholaminergic and serotonergic neurons work on a higher activity level, we compared the amount of norepinephrine, dopamine, and serotonin released from selected discrete brain areas isolated from the brain of sated and food-deprived rats. Rats were deprived of food for 48 and 72 hours, respectively, and the state of excitability of their catecholaminergic and serotonergic neurons in comparison to that of sated rats was measured. We tested the orienting-searching reflex activity of the rats in a special open field, isolated thereafter selected discrete brain areas and measured the release of norepinephrine, dopamine, and serotonin from the proper tissue samples into the organ bath. The orienting-searching reflex activity of the rats increased proportionally to the time elapsed from the last feed and the amount of dopamine released from the striatum, substantia nigra and

  4. Comprehensive Evaluation of Neuroprotection Achieved by Extended Selective Brain Cooling Therapy in a Rat Model of Penetrating Ballistic-Like Brain Injury

    Science.gov (United States)

    Shear, Deborah A.; Deng-Bryant, Ying; Leung, Lai Yee; Wei, Guo; Chen, Zhiyong; Tortella, Frank C.

    2016-01-01

    Brain hypothermia has been considered as a promising alternative to whole-body hypothermia in treating acute neurological disease, for example, traumatic brain injury. Previously, we demonstrated that 2-hours selective brain cooling (SBC) effectively mitigated acute (≤24 hours postinjury) neurophysiological dysfunction induced by a penetrating ballistic-like brain injury (PBBI) in rats. This study evaluated neuroprotective effects of extended SBC (4 or 8 hours in duration) on sub-acute secondary injuries between 3 and 21 days postinjury (DPI). SBC (34°C) was achieved via extraluminal cooling of rats' bilateral common carotid arteries (CCA). Depending on the experimental design, SBC was introduced either immediately or with a 2- or 4-hour delay after PBBI and maintained for 4 or 8 hours. Neuroprotective effects of SBC were evaluated by measuring brain lesion volume, axonal injury, neuroinflammation, motor and cognitive functions, and post-traumatic seizures. Compared to untreated PBBI animals, 4 or 8 hours SBC treatment initiated immediately following PBBI produced comparable neuroprotective benefits against PBBI-induced early histopathology at 3 DPI as evidenced by significant reductions in brain lesion volume, axonal pathology (beta-amyloid precursor protein staining), neuroinflammation (glial fibrillary acetic protein stained-activated astrocytes and rat major histocompatibility complex class I stained activated microglial cell), and post-traumatic nonconvulsive seizures. In the later phase of the injury (7–21 DPI), significant improvement on motor function (rotarod test) was observed under most SBC protocols, including the 2-hour delay in SBC initiation. However, SBC treatment failed to improve cognitive performance (Morris water maze test) measured 13–17 DPI. The protective effects of SBC on delayed axonal injury (silver staining) were evident out to 14 DPI. In conclusion, the CCA cooling method of SBC produced neuroprotection measured across multiple

  5. Resting Brain Perfusion and Selected Vascular Risk Factors in Healthy Elderly Subjects

    DEFF Research Database (Denmark)

    Henriksen, Otto M.; Jensen, Lars T; Krabbe, Katja

    2014-01-01

    with circulating homocysteine, but not with asymmetric dimethylarginine, dyslipidemia or the carotid intima-media thickness. The relative regional brain perfusion was associated with circulating homocysteine, with a relative parietal hypoperfusion and a frontal hyperperfusion. No effect on regional brain perfusion...... was observed for any of the other risk factors. A multiple regression model including homocysteine, caffeine, hematocrit and end-tidal PCO2, explained nearly half of the observed variability. CONCLUSION: Both intrinsic and extrinsic factors influenced global cerebral perfusion variation between subjects....... Further, the results suggest that the inverse relation between homocysteine and brain perfusion is owing to other mechanisms, than reflected by asymmetric dimethylarginine, and that homocysteine may be a marker of cerebral perfusion in aging brains....

  6. Can you hear me now? Musical training shapes functional brain networks for selective auditory attention and hearing speech in noise

    Directory of Open Access Journals (Sweden)

    Dana L Strait

    2011-06-01

    Full Text Available Even in the quietest of rooms, our senses are perpetually inundated by a barrage of sounds, requiring the auditory system to adapt to a variety of listening conditions in order to extract signals of interest (e.g., one speaker’s voice amidst others. Brain networks that promote selective attention are thought to sharpen the neural encoding of a target signal, suppressing competing sounds and enhancing perceptual performance. Here, we ask: does musical training benefit cortical mechanisms that underlie selective attention to speech? To answer this question, we assessed the impact of selective auditory attention on cortical auditory-evoked response variability in musicians and nonmusicians. Outcomes indicate strengthened brain networks for selective auditory attention in musicians in that musicians but not nonmusicians demonstrate decreased prefrontal response variability with auditory attention. Results are interpreted in the context of previous work from our laboratory documenting perceptual and subcortical advantages in musicians for the hearing and neural encoding of speech in background noise. Musicians’ neural proficiency for selectively engaging and sustaining auditory attention to language indicates a potential benefit of music for auditory training. Given the importance of auditory attention for the development of language-related skills, musical training may aid in the prevention, habilitation and remediation of children with a wide range of attention-based language and learning impairments.

  7. Brain region specific mitophagy capacity could contribute to selective neuronal vulnerability in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Zabel Claus

    2011-09-01

    Full Text Available Abstract Parkinson's disease (PD is histologically well defined by its characteristic degeneration of dopaminergic neurons in the substantia nigra pars compacta. Remarkably, divergent PD-related mutations can generate comparable brain region specific pathologies. This indicates that some intrinsic region-specificity respecting differential neuron vulnerability exists, which codetermines the disease progression. To gain insight into the pathomechanism of PD, we investigated protein expression and protein oxidation patterns of three different brain regions in a PD mouse model, the PINK1 knockout mice (PINK1-KO, in comparison to wild type control mice. The dysfunction of PINK1 presumably affects mitochondrial turnover by disturbing mitochondrial autophagic pathways. The three brain regions investigated are the midbrain, which is the location of substantia nigra; striatum, the major efferent region of substantia nigra; and cerebral cortex, which is more distal to PD pathology. In all three regions, mitochondrial proteins responsible for energy metabolism and membrane potential were significantly altered in the PINK1-KO mice, but with very different region specific accents in terms of up/down-regulations. This suggests that disturbed mitophagy presumably induced by PINK1 knockout has heterogeneous impacts on different brain regions. Specifically, the midbrain tissue seems to be most severely hit by defective mitochondrial turnover, whereas cortex and striatum could compensate for mitophagy nonfunction by feedback stimulation of other catabolic programs. In addition, cerebral cortex tissues showed the mildest level of protein oxidation in both PINK1-KO and wild type mice, indicating either a better oxidative protection or less reactive oxygen species (ROS pressure in this brain region. Ultra-structural histological examination in normal mouse brain revealed higher incidences of mitophagy vacuoles in cerebral cortex than in striatum and substantia

  8. Nicotine affects rat Leydig cell function in vivo and vitro via down-regulating some key steroidogenic enzyme expressions.

    Science.gov (United States)

    Guo, Xiaoling; Wang, Huang; Wu, Xiaolong; Chen, Xianwu; Chen, Yong; Guo, Jingjing; Li, Xiaoheng; Lian, Qingquan; Ge, Ren-Shan

    2017-12-01

    Nicotine is consumed largely as a component of cigarettes and has a potential effect on pubertal development of Leydig cells in males. To investigate its effects, 49-day-old male Sprague Dawley rats received intraperitoneal injections of nicotine (0.5 or 1 mg/kg/day) for 2 weeks and immature Leydig cells were isolated from the testes of 35-day-old rats and treated with nicotine (0.05-50 μM). Serum hormones, Leydig cell number and related gene expression levels after in vivo treatment were determined and medium androgen levels were measured and cell cycle, apoptosis, mitochondrial membrane potential (△Ψm), and reactive oxygen species (ROS) of Leydig cells after in vitro treatment were measured. In vivo exposure to nicotine lowered serum luteinizing hormone, follicle stimulating hormone, and testosterone levels and reduced Leydig cell number and gene expression levels. Nicotine in vitro inhibited androgen production in Leydig cells by downregulating the expression levels of P450 cholesterol side cleavage enzyme, 3β-hydroxysteroid dehydrogenase 1, and steroidogenic factor 1 at different concentration ranges. In conclusion, nicotine disrupts Leydig cell steroidogenesis during puberty possibly via down-regulating some key steroidogenic enzyme expressions. Copyright © 2017. Published by Elsevier Ltd.

  9. Degree of contribution (DoC) feature selection algorithm for structural brain MRI volumetric features in depression detection.

    Science.gov (United States)

    Kipli, Kuryati; Kouzani, Abbas Z

    2015-07-01

    Accurate detection of depression at an individual level using structural magnetic resonance imaging (sMRI) remains a challenge. Brain volumetric changes at a structural level appear to have importance in depression biomarkers studies. An automated algorithm is developed to select brain sMRI volumetric features for the detection of depression. A feature selection (FS) algorithm called degree of contribution (DoC) is developed for selection of sMRI volumetric features. This algorithm uses an ensemble approach to determine the degree of contribution in detection of major depressive disorder. The DoC is the score of feature importance used for feature ranking. The algorithm involves four stages: feature ranking, subset generation, subset evaluation, and DoC analysis. The performance of DoC is evaluated on the Duke University Multi-site Imaging Research in the Analysis of Depression sMRI dataset. The dataset consists of 115 brain sMRI scans of 88 healthy controls and 27 depressed subjects. Forty-four sMRI volumetric features are used in the evaluation. The DoC score of forty-four features was determined as the accuracy threshold (Acc_Thresh) was varied. The DoC performance was compared with that of four existing FS algorithms. At all defined Acc_Threshs, DoC outperformed the four examined FS algorithms for the average classification score and the maximum classification score. DoC has a good ability to generate reduced-size subsets of important features that could yield high classification accuracy. Based on the DoC score, the most discriminant volumetric features are those from the left-brain region.

  10. It's in the eye of the beholder: selective attention to drink properties during tasting influences brain activation in gustatory and reward regions.

    Science.gov (United States)

    van Rijn, Inge; de Graaf, Cees; Smeets, Paul A M

    2018-04-01

    Statements regarding pleasantness, taste intensity or caloric content on a food label may influence the attention consumers pay to such characteristics during consumption. There is little research on the effects of selective attention on taste perception and associated brain activation in regular drinks. The aim of this study was to investigate the effect of selective attention on hedonics, intensity and caloric content on brain responses during tasting drinks. Using functional MRI brain responses of 27 women were measured while they paid attention to the intensity, pleasantness or caloric content of fruit juice, tomato juice and water. Brain activation during tasting largely overlapped between the three selective attention conditions and was found in the rolandic operculum, insula and overlying frontal operculum, striatum, amygdala, thalamus, anterior cingulate cortex and middle orbitofrontal cortex (OFC). Brain activation was higher during selective attention to taste intensity compared to calories in the right middle OFC and during selective attention to pleasantness compared to intensity in the right putamen, right ACC and bilateral middle insula. Intensity ratings correlated with brain activation during selective attention to taste intensity in the anterior insula and lateral OFC. Our data suggest that not only the anterior insula but also the middle and lateral OFC are involved in evaluating taste intensity. Furthermore, selective attention to pleasantness engaged regions associated with food reward. Overall, our results indicate that selective attention to food properties can alter the activation of gustatory and reward regions. This may underlie effects of food labels on the consumption experience of consumers.

  11. Preparation of new technetium-99m NNS/X complexes and selection for brain imaging agent

    Institute of Scientific and Technical Information of China (English)

    HE; Qiange; CHEN; Xiangji; MIAO; Yubin; LIU; Boli

    2004-01-01

    Based on excellent experiment results of 99mTcO-MPBDA-Cl, two new ligands MPTDA and MPDAA are synthesized. Then series of 99mTcO3+ complexes are prepared through adding different halide anions, followed by tests of physical chemistry qualities and biodistribution experiments. And results of these experiments show that complexes formed with MPTDA and MPDAA have better lipophilicity than those formed with MPBDA, still maintain the good brain retention ability of this type of compounds, but radioactivity uptake in blood is higher than that of 99mTcO-MPBDA and ratios of brain/blood are reduced. Obvious affections are fetched out on brain uptake and retention if fluoride, bromide or iodide anions are added. Results of experiments can be explained in reason with theoretic computation. It is confirmed that 99mTcO-MPBDA-Cl has potential to develop a new type of brain imaging agent considering integrated factors such as brain uptake, retention and toxicity.

  12. Violence: heightened brain attentional network response is selectively muted in Down syndrome.

    Science.gov (United States)

    Anderson, Jeffrey S; Treiman, Scott M; Ferguson, Michael A; Nielsen, Jared A; Edgin, Jamie O; Dai, Li; Gerig, Guido; Korenberg, Julie R

    2015-01-01

    The ability to recognize and respond appropriately to threat is critical to survival, and the neural substrates subserving attention to threat may be probed using depictions of media violence. Whether neural responses to potential threat differ in Down syndrome is not known. We performed functional MRI scans of 15 adolescent and adult Down syndrome and 14 typically developing individuals, group matched by age and gender, during 50 min of passive cartoon viewing. Brain activation to auditory and visual features, violence, and presence of the protagonist and antagonist were compared across cartoon segments. fMRI signal from the brain's dorsal attention network was compared to thematic and violent events within the cartoons between Down syndrome and control samples. We found that in typical development, the brain's dorsal attention network was most active during violent scenes in the cartoons and that this was significantly and specifically reduced in Down syndrome. When the antagonist was on screen, there was significantly less activation in the left medial temporal lobe of individuals with Down syndrome. As scenes represented greater relative threat, the disparity between attentional brain activation in Down syndrome and control individuals increased. There was a reduction in the temporal autocorrelation of the dorsal attention network, consistent with a shortened attention span in Down syndrome. Individuals with Down syndrome exhibited significantly reduced activation in primary sensory cortices, and such perceptual impairments may constrain their ability to respond to more complex social cues such as violence. These findings may indicate a relative deficit in emotive perception of violence in Down syndrome, possibly mediated by impaired sensory perception and hypoactivation of medial temporal structures in response to threats, with relative preservation of activity in pro-social brain regions. These findings indicate that specific genetic differences associated

  13. The selective value of computed tomography of the brain in Cerebritis due to systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Gaylis, N.B.; Altman, R.D.; Ostrov, S.; Quencer, R.

    1982-01-01

    Systemic lupus erythematosus (SLE) and steroid effects on the brain were measured by computed tomography (CT). Of 14 patients with SLE cerebritis, 10 (71%) had marked cortical atrophy and 4 (29%) minimal atrophy. None were normal by CT. Controls included 22 patients with SLE without cerebritis receiving cortiocosteroids; this group had normal CT scans in 16 (73%) and minimal cortical atrophy in the remaining 6 (27%). Follow-up CT on 5 patients with cerebritis was unchanged. CT of the brain is a minimally invasive technique for documenting SLE cerebritis. CT may also help differentiate cerebritis from the neuropsychiatric side effects of corticosteroids

  14. Increased orbitofrontal brain activation after administration of a selective adenosine A2A antagonist in cocaine dependent subjects

    Directory of Open Access Journals (Sweden)

    F. Gerard eMoeller

    2012-05-01

    Full Text Available Background: Positron Emission Tomography imaging studies provide evidence of reduced dopamine function in cocaine dependent subjects in the striatum, which is correlated with prefrontal cortical glucose metabolism, particularly in the orbitofrontal cortex. However, whether enhancement of dopamine in the striatum in cocaine dependent subjects would be associated with changes in prefrontal cortical brain activation is unknown. One novel class of medications that enhance dopamine function via heteromer formation with dopamine receptors in the striatum is the selective adenosine A2A receptor antagonists. This study sought to determine the effects administration of the selective adenosine A2A receptor antagonist SYN115 on brain function in cocaine dependent subjects. Methodology/Principle Findings: Twelve cocaine dependent subjects underwent two fMRI scans (one after a dose of placebo and one after a dose of 100 mg of SYN115 while performing a working memory task with 3 levels of difficulty (3, 5, and 7 digits. fMRI results showed that for 7-digit working memory activation there was significantly greater activation from SYN115 compared to placebo in portions of left (L lateral orbitofrontal cortex, L insula, and L superior and middle temporal pole. Conclusion/Significance: These findings are consistent with enhanced dopamine function in the striatum in cocaine dependent subjects via blockade of adenosine A2A receptors producing increased brain activation in the orbitofrontal cortex and other cortical regions. This suggests that at least some of the changes in brain activation in prefrontal cortical regions in cocaine dependent subjects may be related to altered striatal dopamine function, and that enhancement of dopamine function via adenosine A2A receptor blockade could be explored further for amelioration of neurobehavioral deficits associated with chronic cocaine use.

  15. Selectively stimulating neural populations in the subthalamic region using a novel deep brain stimulation lead design

    NARCIS (Netherlands)

    van Dijk, Kees Joab; Verhagen, R.; Bour, L.J.; Heida, Tjitske

    2013-01-01

    Deep brain stimulation (DBS) of the Subthalamic Nucleus (STN) is widely used in advanced stages of Parkinson's disease(PD) and has proven to be an effective treatment of the various motor symptoms. The therapy involves implanting a lead consisting of multiple electrodes in the STN through which

  16. Nonspatial intermodal selective attention is mediated by sensory brain areas: Evidence from event-related potential.

    NARCIS (Netherlands)

    Talsma, D.; Kok, A.

    2001-01-01

    Focuses on the question of whether inter-and intramodal forms of attention are reflected in activation of the same or different brain areas. ERPs were recorded while Ss (aged 18-41 yrs) were presented a random sequence of visual and auditory stimuli. They were instructed to attend to nonspatial

  17. Nonspatial intermodal selective attention is mediated by sensory brain areas: Evidence from event-related potentials

    NARCIS (Netherlands)

    Talsma, D.; Kok, Albert

    2001-01-01

    The present study focuses on the question of whether inter- and intramodal forms of attention are reflected in activation of the same or different brain areas. ERPs were recorded while subjects were presented a random sequence of visual and auditory stimuli. They were instructed to attend to

  18. Performance of Brain-computer Interfacing based on tactile selective sensation and motor imagery

    DEFF Research Database (Denmark)

    Yao, Lin; Sheng, Xinjun; Mrachacz-Kersting, Natalie

    2018-01-01

    We proposed a multi-class tactile brain-computer interface that utilizes stimulus-induced oscillatory dynamics. It was hypothesized that somatosensory attention can modulate tactile induced oscillation changes, which can decode different sensation attention tasks. Subjects performed four tactile...

  19. A novel lead design enables selective deep brain stimulation of neural populations in the subthalamic region

    NARCIS (Netherlands)

    van Dijk, Kees J.; Verhagen, Rens; Chaturvedi, Ashutosh; McIntyre, Cameron C.; Bour, Lo J.; Heida, Ciska; Veltink, Peter H.

    2015-01-01

    The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) as a treatment for Parkinson's disease are sensitive to the location of the DBS lead within the STN. New high density (HD) lead designs have been created which are hypothesized to provide additional degrees of

  20. A novel lead design enables selective deep brain stimulation of neural populations in the subthalamic region

    NARCIS (Netherlands)

    van Dijk, Kees J.; Verhagen, Rens; Chaturvedi, Ashutosh; McIntyre, Cameron C.; Bour, Lo J.; Heida, Tjitske; Veltink, Peter H.

    2015-01-01

    Objective. The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) as a treatment for Parkinson's disease are sensitive to the location of the DBS lead within the STN. New high density (HD) lead designs have been created which are hypothesized to provide additional

  1. Differential targeting of brain stress circuits with a selective glucocorticoid receptor modulator

    NARCIS (Netherlands)

    Zalachoras, I.; Houtman, R.; Atucha, E.; Devos, R.; Tijssen, A.M.I.; Hu, P.; Lockey, P.M.; Datson, N.A.; Belanoff, J.K.; Lucassen, P.J.; Joëls, M.; de Kloet, E.R.; Roozendaal, B.; Hunt, H.; Meijer, O.C.

    2013-01-01

    Glucocorticoid receptor (GR) antagonism may be of considerable therapeutic value in stress-related psychopathology such as depression. However, blockade of all GR-dependent processes in the brain will lead to unnecessary and even counteractive effects, such as elevated endogenous cortisol levels.

  2. Selection of appropriate template for spatial normalization of brain images: tensor based morphometry

    International Nuclear Information System (INIS)

    Lee, Jae Sung; Lee, Dong Soo; Kim, Yu Kyeong; Chung, June Key; Lee, Myung Chul

    2004-01-01

    Although there have been remarkable advances in spatial normalization techniques, the differences in the shape of the hemispheres and the sulcal pattern of brains relative to age, gender, races, and diseases cannot be fully overcome by the nonlinear spatial normalization techniques. T1 SPGR MR images in 16 elderly male normal volunteers (>55 y. mean age: = 61.8 ± 3.5 y) were spatially normalized onto the age/gender specific Korean templates, and the Caucasian MNI template and the extent of the deformations were compared. These particular subjects were never included in the development of the templates. First , the images were matched into the templates using an affine transformation to eliminate the global difference between the templates and source images. Second the affine registration was followed by an estimation of nonlinear deformation. Determinants of the Jacobian matrices of the nonlinear deformation were then calculated for every voxel to estimate the regional volume change during the nonlinear transformation Jacobian determinant images highlighted the great magnitude of the relative local volume changes obtained when the elderly brains were spatially normalized onto the young/midlife male or female templates. They reflect the enlargement of CSF space in the lateral ventricles, sylvian fissures and cisterna magna, and the shrinkage of the cortex noted mainly in frontal, insular and lateral temporal cortexes, and the cerebellums in the aged brains. In the Jacobian determinant images, a regional shrinkage of the brain in the left middle prefrontal cortex was observed in addition to the regional expansion in the ventricles and sylvian fissures, which may be due to the age differences between the template and source images. The regional anatomical difference between template and source images could impose an extreme deformation of the source images during the spatial normalization and therefore. Individual brains should be placed into the appropriate template

  3. Selection of appropriate template for spatial normalization of brain images: tensor based morphometry

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Sung; Lee, Dong Soo; Kim, Yu Kyeong; Chung, June Key; Lee, Myung Chul [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

    2004-07-01

    Although there have been remarkable advances in spatial normalization techniques, the differences in the shape of the hemispheres and the sulcal pattern of brains relative to age, gender, races, and diseases cannot be fully overcome by the nonlinear spatial normalization techniques. T1 SPGR MR images in 16 elderly male normal volunteers (>55 y. mean age: = 61.8 {+-} 3.5 y) were spatially normalized onto the age/gender specific Korean templates, and the Caucasian MNI template and the extent of the deformations were compared. These particular subjects were never included in the development of the templates. First , the images were matched into the templates using an affine transformation to eliminate the global difference between the templates and source images. Second the affine registration was followed by an estimation of nonlinear deformation. Determinants of the Jacobian matrices of the nonlinear deformation were then calculated for every voxel to estimate the regional volume change during the nonlinear transformation Jacobian determinant images highlighted the great magnitude of the relative local volume changes obtained when the elderly brains were spatially normalized onto the young/midlife male or female templates. They reflect the enlargement of CSF space in the lateral ventricles, sylvian fissures and cisterna magna, and the shrinkage of the cortex noted mainly in frontal, insular and lateral temporal cortexes, and the cerebellums in the aged brains. In the Jacobian determinant images, a regional shrinkage of the brain in the left middle prefrontal cortex was observed in addition to the regional expansion in the ventricles and sylvian fissures, which may be due to the age differences between the template and source images. The regional anatomical difference between template and source images could impose an extreme deformation of the source images during the spatial normalization and therefore. Individual brains should be placed into the appropriate

  4. Amygdala activation as a marker for selective attention toward neutral faces in a chronic traumatic brain injury population.

    Science.gov (United States)

    Young, Leanne R; Yu, Weikei; Holloway, Michael; Rodgers, Barry N; Chapman, Sandra B; Krawczyk, Daniel C

    2017-09-01

    There has been great interest in characterizing the response of the amygdala to emotional faces, especially in the context of social cognition. Although amygdala activation is most often associated with fearful or angry stimuli, there is considerable evidence that the response of the amygdala to neutral faces is both robust and reliable. This characteristic of amygdala function is of particular interest in the context of assessing populations with executive function deficits, such as traumatic brain injuries, which can be evaluated using fMRI attention modulation tasks that evaluate prefrontal control over representations, notably faces. The current study tested the hypothesis that the amygdala may serve as a marker of selective attention to neutral faces. Using fMRI, we gathered data within a chronic traumatic brain injury population. Blood Oxygenation Level Dependent (BOLD) signal change within the left and right amygdalae and fusiform face areas was measured while participants viewed neutral faces and scenes, under conditions requiring participants to (1) categorize pictures of faces and scenes, (2) selectively attend to either faces or scenes, or (3) attend to both faces and scenes. Findings revealed that the amygdala is an effective marker for selective attention to neutral faces and, furthermore, it was more face-specific than the fusiform face area. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Use of Multichannel Near Infrared Spectroscopy to Study Relationships Between Brain Regions and Neurocognitive Tasks of Selective/Divided Attention and 2-Back Working Memory.

    Science.gov (United States)

    Tomita, Nozomi; Imai, Shoji; Kanayama, Yusuke; Kawashima, Issaku; Kumano, Hiroaki

    2017-06-01

    While dichotic listening (DL) was originally intended to measure bottom-up selective attention, it has also become a tool for measuring top-down selective attention. This study investigated the brain regions related to top-down selective and divided attention DL tasks and a 2-back task using alphanumeric and Japanese numeric sounds. Thirty-six healthy participants underwent near-infrared spectroscopy scanning while performing a top-down selective attentional DL task, a top-down divided attentional DL task, and a 2-back task. Pearson's correlations were calculated to show relationships between oxy-Hb concentration in each brain region and the score of each cognitive task. Different brain regions were activated during the DL and 2-back tasks. Brain regions activated in the top-down selective attention DL task were the left inferior prefrontal gyrus and left pars opercularis. The left temporopolar area was activated in the top-down divided attention DL task, and the left frontopolar area and left dorsolateral prefrontal cortex were activated in the 2-back task. As further evidence for the finding that each task measured different cognitive and brain area functions, neither the percentages of correct answers for the three tasks nor the response times for the selective attentional task and the divided attentional task were correlated to one another. Thus, the DL and 2-back tasks used in this study can assess multiple areas of cognitive, brain-related dysfunction to explore their relationship to different psychiatric and neurodevelopmental disorders.

  6. Selective Toll-Like Receptor 4 Antagonists Prevent Acute Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in Mice.

    Science.gov (United States)

    Okada, Takeshi; Kawakita, Fumihiro; Nishikawa, Hirofumi; Nakano, Fumi; Liu, Lei; Suzuki, Hidenori

    2018-05-31

    There are no direct evidences showing the linkage between Toll-like receptor 4 (TLR4) and blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH). The purpose of this study was to examine if selective blockage of TLR4 prevents BBB disruption after SAH in mice and if the TLR4 signaling involves mitogen-activated protein kinases (MAPKs). One hundred and fifty-one C57BL/6 male mice underwent sham or endovascular perforation SAH operation, randomly followed by an intracerebroventricular infusion of vehicle or two dosages (117 or 585 ng) of a selective TLR4 antagonist IAXO-102 at 30 min post-operation. The effects were evaluated by survival rates, neurological scores, and brain water content at 24-72 h and immunoglobulin G immunostaining and Western blotting at 24 h post-SAH. IAXO-102 significantly prevented post-SAH neurological impairments, brain edema, and BBB disruption, resulting in improved survival rates. IAXO-102 also significantly suppressed post-SAH activation of a major isoform of MAPK p46 c-Jun N-terminal kinase (JNK) and matrix metalloproteinase-9 as well as periostin induction and preserved tight junction protein zona occludens-1. Another selective TLR4 antagonist TAK-242, which has a different binding site from IAXO-102, also showed similar effects to IAXO-102. This study first provided the evidence that TLR4 signaling is involved in post-SAH acute BBB disruption and that the signaling is mediated at least partly by JNK activation. TLR4-targeted therapy may be promising to reduce post-SAH morbidities and mortalities.

  7. Brain superoxide anion formation in immature rats during seizures: Protection by selected compounds

    Czech Academy of Sciences Publication Activity Database

    Folbergrová, Jaroslava; Otáhal, Jakub; Druga, Rastislav

    2012-01-01

    Roč. 233, č. 1 (2012), s. 421-429 ISSN 0014-4886 R&D Projects: GA ČR GA309/08/0292; GA ČR GAP303/10/0999 Institutional research plan: CEZ:AV0Z50110509 Keywords : immature rats * DL-homocysteic acid-induced seizures * superoxide anion * SOD mimetics * protection * Fluoro-Jade B staining * brain damage Subject RIV: FH - Neurology Impact factor: 4.645, year: 2012

  8. Selective brain lesions reduce morphine- and radiation-induced locomotor hyperactivity of the C57BL/6J mouse

    International Nuclear Information System (INIS)

    Mickley, G.A.; Stevens, K.E.; White, G.A.; Gibbs, G.L.

    1984-01-01

    The apparent resemblance between the stereotypic locomotor hyperactivity observed after either an injection of morphine or irradiation of the C57BL/6J mouse has suggested the possibility of similar biochemical and neuroanatomical substrates of these behaviors. In this study the authors made selective brain lesions in an attempt to reverse the locomotor response observed after morphine (30 mg/kg) or radiation (1500 rads /sup 60/Co) treatments. Lesions impinging on both the dorso-medial caudate and lateral septal nuclei caused a significant decrease in morphine-induced and radiogenic locomotion. Lesions of the individual brain areas did not significantly alter the opiate locomotor response. This reduction in locomotion could not be attributed to a generalized post-surgical lethargy since other brain lesions of similar size did not significantly suppress these behaviors. These data suggest the possibility of some common central nervous system mechanisms which may support the stereotypic locomotor hyperactivity observed in the C57BL/6J mouse after either morphine or radiation treatment

  9. Infantile 4-tert-octylphenol exposure transiently inhibits rat ovarian steroidogenesis and steroidogenic acute regulatory protein (StAR) expression

    International Nuclear Information System (INIS)

    Myllymaeki, S.A.; Karjalainen, M.; Haavisto, T.E.; Toppari, J.; Paranko, J.

    2005-01-01

    Phenolic compounds, such as 4-tert-octylphenol (OP), have been shown to interfere with rat ovarian steroidogenesis. However, little is known about steroidogenic effects of infantile OP exposure on immature ovary. The aim of the present study was to investigate the effects of infantile OP exposure on plasma FSH, LH, estradiol, and progesterone levels in 14-day-old female rats. The effect on ovarian steroidogenic acute regulatory protein (StAR) and FSH receptor (FSHr) expression was analyzed by Western blotting. Ex vivo analysis was carried out for follicular estradiol, progesterone, testosterone, and cAMP production. Sprague-Dawley rats were given OP (0, 10, 50, or 100 mg/kg) subcutaneously on postnatal days 6, 8, 10, and 12. On postnatal day 14, plasma FSH was decreased and progesterone increased significantly at a dose of 100 mg OP/kg. In addition, the highest OP dose advanced the time of vaginal opening in puberty. OP had no effect on infantile LH and estradiol levels or ovarian FSHr content. Ovarian StAR protein content and ex vivo hormone and cAMP production were decreased at all OP doses compared to controls. However, hormone levels recovered independent on FSH and even increased above the control level during a prolonged culture. On postnatal day 35, no statistically significant differences were seen between control and OP-exposed animals in plasma FSH, LH, estradiol, and progesterone levels, or in ovarian StAR protein content. The results indicate that the effect of OP on the infantile ovary is reversible, while more permanent effects in the hypothalamus and pituitary, as described earlier, are involved in the reduction of circulating FSH levels and premature vaginal opening

  10. CCAAT/enhancer-binding proteins regulate expression of the human steroidogenic acute regulatory protein (StAR) gene.

    Science.gov (United States)

    Christenson, L K; Johnson, P F; McAllister, J M; Strauss, J F

    1999-09-10

    Two putative CCAAT/enhancer-binding protein (C/EBP) response elements were identified in the proximal promoter of the human steroidogenic acute regulatory protein (StAR) gene, which encodes a key protein-regulating steroid hormone synthesis. Expression of C/EBPalpha and -beta increased StAR promoter activity in COS-1 and HepG2 cells. Cotransfection of C/EBPalpha or -beta and steroidogenic factor 1, a transcription factor required for cAMP regulation of StAR expression, into COS-1 augmented 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP)-stimulated promoter activity. When the putative C/EBP response elements were mutated, individually or together, a pronounced decline in basal StAR promoter activity in human granulosa-lutein cells resulted, but the fold stimulation of promoter activity by 8-Br-cAMP was unaffected. Recombinant C/EBPalpha and -beta bound to the two identified sequences but not the mutated elements. Human granulosa-lutein cell nuclear extracts also bound these elements but not the mutated sequences. An antibody to C/EBPbeta, but not C/EBPalpha, supershifted the nuclear protein complex associated with the more distal element. The complex formed by nuclear extracts with the proximal element was not supershifted by either antibody. Western blot analysis revealed the presence of C/EBPalpha and C/EBPbeta in human granulosa-lutein cell nuclear extracts. C/EBPbeta levels were up-regulated 3-fold by 8-Br-cAMP treatment. Our studies demonstrate a role for C/EBPbeta as well as yet to be identified proteins, which can bind to C/EBP response elements, in the regulation of StAR gene expression and suggest a mechanism by which C/EBPbeta participates in the cAMP regulation of StAR gene transcription.

  11. Immunolocalization of steroidogenic enzymes in the corpus luteum and placenta of the Japanese black bear, Ursus thibetanus japonicus, during pregnancy.

    Science.gov (United States)

    Tsubota, T; Taki, S; Nakayama, K; Mason, J I; Kominami, S; Harada, N; Kita, I

    2001-04-01

    The Japanese black bear, Ursus thibetanus japonicus, is a seasonal breeder and shows delayed implantation for several months during pregnancy. The objective of this study was to clarify the steroidogenic capability of the corpus luteum and placenta during pregnancy, including both delayed implantation and fetal development, by immunolocalization of steroidogenic enzymes in these organs of the Japanese black bear. Ovaries and placentae from 15 wild Japanese black bears, which had been killed legally by hunters and were thought to be pregnant, were used in an immunocytochemical study to localize the cholesterol side chain cleavage cytochrome P450 (P450scc), 3beta-hydroxysteroid dehydrogenase (3betaHSD), 17alpha-hydroxylase cytochrome P450 (P450c17) and aromatase cytochrome P450 (P450arom) by the avidin-biotin-peroxidase complex method using polyclonal antisera raised in mammals against P450scc, 3betaHSD, P450c17 and P450arom. P450scc and 3betaHSD were localized in all luteal cells throughout pregnancy. P450c17 was present in a few luteal cells, especially in the outer area of the corpus luteum throughout pregnancy, but the number of positively immunostained cells decreased during the post-implantation period. Cells positively immunostained for P450c17 were significantly smaller than negatively immunostained cells (P black bear, corpora lutea are a source of progesterone which may play an important role in the maintenance of delayed implantation and fetal development during pregnancy. Corpora lutea have a minimum capability to synthesize androgen in small luteal cells and oestrogen in normal-sized luteal cells during pregnancy, and placentae have the ability to synthesize oestrogen during late pregnancy.

  12. Selective labelling of 5-HT{sub 7} receptor recognition sites in rat brain using [{sup 3}H]5-carboxamidotryptamine

    Energy Technology Data Exchange (ETDEWEB)

    Stowe, R.L.; Barnes, N.M. [Department of Pharmacology, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom)

    1998-12-01

    The aim of the present study was to establish a radioligand binding assay to selectively label the native 5-HT{sub 7} receptor expressed in rat brain. In rat whole brain (minus cerebellum and striatum) homogenate, ({+-})-pindolol (10 {mu}M)-insensitive [{sup 3}H]5-CT ([{sup 3}H]5-carboxamidotryptamine; 0.5 nM) specific binding (defined by 5-HT, 10 {mu}M) displayed a pharmacological profile similar to the recombinant 5-HT{sub 7} receptor, although the Hill coefficients for competition curves generated by methiothepin, ritanserin, sumatriptan, clozapine and pimozide were significantly less than unity. In homogenates of rat hypothalamus, ({+-})-pindolol (10 {mu}M)-insensitive [{sup 3}H]5-CT recognition sites also resembled, pharmacologically, the 5-HT{sub 7} receptor, although pimozide still generated Hill coefficients significantly less than unity. Subsequent studies were performed in the additional presence of WAY100635 (100 nM) to prevent [{sup 3}H]5-CT binding to residual, possibly, 5-HT{sub 1A} sites. Competition for this [{sup 3}H]5-CT binding indicated the labelling in whole rat brain homogenate of a homogenous population of sites with the pharmacological profile of the 5-HT{sub 7} receptor. Saturation studies also indicated that ({+-})-pindolol (10 {mu}M)/WAY 100635 (100 nM)-insensitive [{sup 3}H]5-CT binding to homogenates of whole rat brain was saturable and to an apparently homogenous population of sites which were labelled with nanomolar affinity (B{sub max}=33.2{+-}0.7 fmol mg{sup -1} protein, pK{sub d}=8.78{+-}0.05, mean{+-}S.E.M., n=3). The development of this 5-HT{sub 7} receptor binding assay will aid investigation of the rat native 5-HT{sub 7} receptor. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  13. Selective labelling of 5-HT7 receptor recognition sites in rat brain using [3H]5-carboxamidotryptamine

    International Nuclear Information System (INIS)

    Stowe, R.L.; Barnes, N.M.

    1998-01-01

    The aim of the present study was to establish a radioligand binding assay to selectively label the native 5-HT 7 receptor expressed in rat brain. In rat whole brain (minus cerebellum and striatum) homogenate, (±)-pindolol (10 μM)-insensitive [ 3 H]5-CT ([ 3 H]5-carboxamidotryptamine; 0.5 nM) specific binding (defined by 5-HT, 10 μM) displayed a pharmacological profile similar to the recombinant 5-HT 7 receptor, although the Hill coefficients for competition curves generated by methiothepin, ritanserin, sumatriptan, clozapine and pimozide were significantly less than unity. In homogenates of rat hypothalamus, (±)-pindolol (10 μM)-insensitive [ 3 H]5-CT recognition sites also resembled, pharmacologically, the 5-HT 7 receptor, although pimozide still generated Hill coefficients significantly less than unity. Subsequent studies were performed in the additional presence of WAY100635 (100 nM) to prevent [ 3 H]5-CT binding to residual, possibly, 5-HT 1A sites. Competition for this [ 3 H]5-CT binding indicated the labelling in whole rat brain homogenate of a homogenous population of sites with the pharmacological profile of the 5-HT 7 receptor. Saturation studies also indicated that (±)-pindolol (10 μM)/WAY 100635 (100 nM)-insensitive [ 3 H]5-CT binding to homogenates of whole rat brain was saturable and to an apparently homogenous population of sites which were labelled with nanomolar affinity (B max =33.2±0.7 fmol mg -1 protein, pK d =8.78±0.05, mean±S.E.M., n=3). The development of this 5-HT 7 receptor binding assay will aid investigation of the rat native 5-HT 7 receptor. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  14. Selective attention to sound location or pitch studied with event-related brain potentials and magnetic fields.

    Science.gov (United States)

    Degerman, Alexander; Rinne, Teemu; Särkkä, Anna-Kaisa; Salmi, Juha; Alho, Kimmo

    2008-06-01

    Event-related brain potentials (ERPs) and magnetic fields (ERFs) were used to compare brain activity associated with selective attention to sound location or pitch in humans. Sixteen healthy adults participated in the ERP experiment, and 11 adults in the ERF experiment. In different conditions, the participants focused their attention on a designated sound location or pitch, or pictures presented on a screen, in order to detect target sounds or pictures among the attended stimuli. In the Attend Location condition, the location of sounds varied randomly (left or right), while their pitch (high or low) was kept constant. In the Attend Pitch condition, sounds of varying pitch (high or low) were presented at a constant location (left or right). Consistent with previous ERP results, selective attention to either sound feature produced a negative difference (Nd) between ERPs to attended and unattended sounds. In addition, ERPs showed a more posterior scalp distribution for the location-related Nd than for the pitch-related Nd, suggesting partially different generators for these Nds. The ERF source analyses found no source distribution differences between the pitch-related Ndm (the magnetic counterpart of the Nd) and location-related Ndm in the superior temporal cortex (STC), where the main sources of the Ndm effects are thought to be located. Thus, the ERP scalp distribution differences between the location-related and pitch-related Nd effects may have been caused by activity of areas outside the STC, perhaps in the inferior parietal regions.

  15. Normal variation and long-term reproducibility of image-selected in vivo brain MR spectroscopy

    International Nuclear Information System (INIS)

    Smith, M.A.; Porter, D.; Lowry, M.; Ayton, V.; Twelves, C.J.; Richards, M.A.; Garlick, P.; Maisey, M.N.

    1988-01-01

    MR spectroscopy of P-31 in the brain was performed with a 1.5-T MR imaging and spectroscopy system using ISIS with a 5-cm cube. A standardized spectral processing routine was adopted, and the ratios of peak areas were measured. Localized brain spectra were obtained from 17 healthy subjects, of whom ten had undergone repeated investigations after a delay of at least 1 month. The variation among healthy subjects, expressed as the mean +- standard deviation, and the long-term reproducibility, expressed as the coefficient of variation, were as follows: for peak areas phosphocreatine (PCr) Pi 2.46 +- 0.72, 21.3%, for PCr/PME, 1.97 +- 0.62, 16.8%, for PCr/PDE, 0.51 +- 0.07, 8.1%; for PCr/Υ-adenosine triphosphate (ATP), 1.13 + 0.15, 6.3%; for PCr/α-ATP, 1.09 +- 0.21, 10.3%, for PCr/β-ATP, 1.66 +- .027, 10.4%; and for pH, 7.00 +- 0.05, 0.8%

  16. Correction: Cecotti, H. and Rivet, B. Subject Combination and Electrode Selection in Cooperative Brain-Computer Interface Based on Event Related Potentials. Brain Sci. 2014, 4, 335–355

    Directory of Open Access Journals (Sweden)

    Hubert Cecotti

    2014-09-01

    Full Text Available The authors wish to make the following correction to this paper (Cecotti, H.; Rivet, B. Subject Combination and Electrode Selection in Cooperative Brain-Computer Interface Based on Event Related Potentials. Brain Sci. 2014, 4, 335–355: Due to an internal error, the reference numbers in the original published paper were not shown, and the error was not due to the authors. The former main text should be replaced as below.

  17. Addressing the selective role of distinct prefrontal areas in response suppression: A study with brain tumor patients.

    Science.gov (United States)

    Arbula, Sandra; Pacella, Valentina; De Pellegrin, Serena; Rossetto, Marta; Denaro, Luca; D'Avella, Domenico; Della Puppa, Alessandro; Vallesi, Antonino

    2017-06-01

    The diverging evidence for functional localization of response inhibition within the prefrontal cortex might be justified by the still unclear involvement of other intrinsically related cognitive processes like response selection and sustained attention. In this study, the main aim was to understand whether inhibitory impairments, previously found in patients with both left and right frontal lesions, could be better accounted for by assessing these potentially related cognitive processes. We tested 37 brain tumor patients with left prefrontal, right prefrontal and non-prefrontal lesions and a healthy control group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory impairments are likely to cause false alarms, although additionally the former task requires response selection and the latter target detection abilities. Irrespective of the task context, patients with right prefrontal damage showed frequent Go and target omissions, probably due to sustained attention lapses. Left prefrontal patients, on the other hand, showed both Go and target omissions and high false alarm rates to No-Go and warning stimuli, suggesting a decisional rather than an inhibitory impairment. An exploratory whole-brain voxel-based lesion-symptom mapping analysis confirmed the association of left ventrolateral and dorsolateral prefrontal lesions with target discrimination failure, and right ventrolateral and medial prefrontal lesions with target detection failure. Results from this study show how left and right prefrontal areas, which previous research has linked to response inhibition, underlie broader cognitive control processes, particularly involved in response selection and target detection. Based on these findings, we suggest that successful inhibitory control relies on more than one functionally distinct process which, if assessed appropriately, might help us to better understand inhibitory impairments across different pathologies. Copyright © 2017 The Authors

  18. The hemodynamically-regulated vascular microenvironment promotes migration of the steroidogenic tissue during its interaction with chromaffin cells in the zebrafish embryo.

    Directory of Open Access Journals (Sweden)

    Chih-Wei Chou

    Full Text Available BACKGROUND: While the endothelium-organ interaction is critical for regulating cellular behaviors during development and disease, the role of blood flow in these processes is only partially understood. The dorsal aorta performs paracrine functions for the timely migration and differentiation of the sympatho-adrenal system. However, it is unclear how the adrenal cortex and medulla achieve and maintain specific integration and whether hemodynamic forces play a role. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, the possible modulation of steroidogenic and chromaffin cell integration by blood flow was investigated in the teleostean counterpart of the adrenal gland, the interrenal gland, in the zebrafish (Danio rerio. Steroidogenic tissue migration and angiogenesis were suppressed by genetic or pharmacologic inhibition of blood flow, and enhanced by acceleration of blood flow upon norepinephrine treatment. Repressed steroidogenic tissue migration and angiogenesis due to flow deficiency were recoverable following restoration of flow. The regulation of interrenal morphogenesis by blood flow was found to be mediated through the vascular microenvironment and the Fibronectin-phosphorylated Focal Adhesion Kinase (Fn-pFak signaling. Moreover, the knockdown of krüppel-like factor 2a (klf2a or matrix metalloproteinase 2 (mmp2, two genes regulated by the hemodynamic force, phenocopied the defects in migration, angiogenesis, the vascular microenvironment, and pFak signaling of the steroidogenic tissue observed in flow-deficient embryos, indicating a direct requirement of mechanotransduction in these processes. Interestingly, epithelial-type steroidogenic cells assumed a mesenchymal-like character and downregulated β-Catenin at cell-cell junctions during interaction with chromaffin cells, which was reversed by inhibiting blood flow or Fn-pFak signaling. Blood flow obstruction also affected the migration of chromaffin cells, but not through

  19. Face and Word Recognition Can Be Selectively Affected by Brain Injury or Developmental Disorders

    DEFF Research Database (Denmark)

    Robotham, Ro J.; Starrfelt, Randi

    2017-01-01

    Face and word recognition have traditionally been thought to rely on highly specialised and relatively independent cognitive processes. Some of the strongest evidence for this has come from patients with seemingly category-specific visual perceptual deficits such as pure prosopagnosia, a selective...... face recognition deficit, and pure alexia, a selective word recognition deficit. Together, the patterns of impaired reading with preserved face recognition and impaired face recognition with preserved reading constitute a double dissociation. The existence of these selective deficits has been...... also have deficits in the other. The implications of this would be immense, with most textbooks in cognitive neuropsychology requiring drastic revisions. In order to evaluate the evidence for dissociations, we review studies that specifically investigate whether face or word recognition can...

  20. Selective effects of alpha-MSH and MIF-1 on the blood-brain barrier

    International Nuclear Information System (INIS)

    Sankar, R.; Domer, F.R.; Kastin, A.J.

    1981-01-01

    The effects of intravenously-injected alpha-MSH and MIF-1 (Pro-Leu-Gly-NH2) on the permeability of the blood-brain barrier (BBB) to a large protein and a small anion were studied using radioiodinated serum albumin (RISA) and 99mTc-labeled sodium pertechnetate. The permeability of the BBB to RISA was unaltered by either peptide. Permeability to the inorganic pertechnetate anion, however, was significantly increased by alpha-MSH but not by MIF-1 at doses known to evoke EEG and behavioral responses. The peptides did not cause a change in the systemic blood pressure. It is possible, therefore, that at least some CNS effects of peripherally administered peptides are exerted by alteration of the permeability of the BBB to other substances

  1. Estrogen alters the diurnal rhythm of alpha 1-adrenergic receptor densities in selected brain regions

    Energy Technology Data Exchange (ETDEWEB)

    Weiland, N.G.; Wise, P.M.

    1987-11-01

    Norepinephrine regulates the proestrous and estradiol-induced LH surge by binding to alpha 1-adrenergic receptors. The density of alpha 1-receptors may be regulated by estradiol, photoperiod, and noradrenergic neuronal activity. We wished to determine whether alpha 1-receptors exhibit a diurnal rhythm in ovariectomized and/or estradiol-treated female rats, whether estradiol regulates alpha 1-receptors in those areas of brain involved with LH secretion and/or sexual behavior, and whether the concentrations of alpha-receptors vary inversely relative to previously reported norepinephrine turnover patterns. Young female rats, maintained on a 14:10 light-dark cycle were ovariectomized. One week later, half of them were outfitted sc with Silastic capsules containing estradiol. Groups of animals were decapitated 2 days later at 0300, 1000, 1300, 1500, 1800, and 2300 h. Brains were removed, frozen, and sectioned at 20 micron. Sections were incubated with (/sup 3/H)prazosin in Tris-HCl buffer, washed, dried, and exposed to LKB Ultrofilm. The densities of alpha 1-receptors were quantitated using a computerized image analysis system. In ovariectomized rats, the density of alpha 1-receptors exhibited a diurnal rhythm in the suprachiasmatic nucleus (SCN), medial preoptic nucleus (MPN), and pineal gland. In SCN and MPN, receptor concentrations were lowest during the middle of the day and rose to peak levels at 1800 h. In the pineal gland, the density of alpha 1-receptors was lowest at middark phase, rose to peak levels before lights on, and remained elevated during the day. Estradiol suppressed the density of alpha 1 binding sites in the SCN, MPN, median eminence, ventromedial nucleus, and the pineal gland but had no effect on the lateral septum. Estrogen treatment altered the rhythm of receptor densities in MPN, median eminence, and the pineal gland.

  2. Estrogen alters the diurnal rhythm of alpha 1-adrenergic receptor densities in selected brain regions

    International Nuclear Information System (INIS)

    Weiland, N.G.; Wise, P.M.

    1987-01-01

    Norepinephrine regulates the proestrous and estradiol-induced LH surge by binding to alpha 1-adrenergic receptors. The density of alpha 1-receptors may be regulated by estradiol, photoperiod, and noradrenergic neuronal activity. We wished to determine whether alpha 1-receptors exhibit a diurnal rhythm in ovariectomized and/or estradiol-treated female rats, whether estradiol regulates alpha 1-receptors in those areas of brain involved with LH secretion and/or sexual behavior, and whether the concentrations of alpha-receptors vary inversely relative to previously reported norepinephrine turnover patterns. Young female rats, maintained on a 14:10 light-dark cycle were ovariectomized. One week later, half of them were outfitted sc with Silastic capsules containing estradiol. Groups of animals were decapitated 2 days later at 0300, 1000, 1300, 1500, 1800, and 2300 h. Brains were removed, frozen, and sectioned at 20 micron. Sections were incubated with [ 3 H]prazosin in Tris-HCl buffer, washed, dried, and exposed to LKB Ultrofilm. The densities of alpha 1-receptors were quantitated using a computerized image analysis system. In ovariectomized rats, the density of alpha 1-receptors exhibited a diurnal rhythm in the suprachiasmatic nucleus (SCN), medial preoptic nucleus (MPN), and pineal gland. In SCN and MPN, receptor concentrations were lowest during the middle of the day and rose to peak levels at 1800 h. In the pineal gland, the density of alpha 1-receptors was lowest at middark phase, rose to peak levels before lights on, and remained elevated during the day. Estradiol suppressed the density of alpha 1 binding sites in the SCN, MPN, median eminence, ventromedial nucleus, and the pineal gland but had no effect on the lateral septum. Estrogen treatment altered the rhythm of receptor densities in MPN, median eminence, and the pineal gland

  3. Natural selection constrains personality and brain gene expression differences in Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Thörnqvist, Per-Ove; Höglund, Erik; Winberg, Svante

    2015-04-01

    In stream-spawning salmonid fishes there is a considerable variation in the timing of when fry leave the spawning nests and establish a feeding territory. The timing of emergence from spawning nests appears to be related to behavioural and physiological traits, e.g. early emerging fish are bolder and more aggressive. In the present study, emerging Atlantic salmon (Salmo salar L.) alevins were sorted into three fractions: early, intermediate and late emerging. At the parr stage, behaviour, stress responses, hindbrain monoaminergic activity and forebrain gene expression were explored in fish from the early and late emerging fractions (first and last 25%). The results show that when subjected to confinement stress, fish from the late emerging fraction respond with a larger activation of the brain serotonergic system than fish from the early fraction. Similarly, in late emerging fish, stress resulted in elevated expression of mRNA coding for serotonin 1A receptors (5-HT1A), GABA-A receptor-associated protein and ependymin, effects not observed in fish from the early emerging fraction. Moreover, fish from the early emerging fraction displayed bolder behaviour than their late emerging littermates. Taken together, these results suggest that time of emergence, boldness and aggression are linked to each other, forming a behavioural syndrome in juvenile salmon. Differences in brain gene expression between early and late emerging salmon add further support to a relationship between stress coping style and timing of emergence. However, early and late emerging salmon do not appear to differ in hypothalamus-pituitary-interrenal (HPI) axis reactivity, another characteristic of divergent stress coping styles. © 2015. Published by The Company of Biologists Ltd.

  4. Places in the Brain: Bridging Layout and Object Geometry in Scene-Selective Cortex.

    Science.gov (United States)

    Dillon, Moira R; Persichetti, Andrew S; Spelke, Elizabeth S; Dilks, Daniel D

    2017-06-13

    Diverse animal species primarily rely on sense (left-right) and egocentric distance (proximal-distal) when navigating the environment. Recent neuroimaging studies with human adults show that this information is represented in 2 scene-selective cortical regions-the occipital place area (OPA) and retrosplenial complex (RSC)-but not in a third scene-selective region-the parahippocampal place area (PPA). What geometric properties, then, does the PPA represent, and what is its role in scene processing? Here we hypothesize that the PPA represents relative length and angle, the geometric properties classically associated with object recognition, but only in the context of large extended surfaces that compose the layout of a scene. Using functional magnetic resonance imaging adaptation, we found that the PPA is indeed sensitive to relative length and angle changes in pictures of scenes, but not pictures of objects that reliably elicited responses to the same geometric changes in object-selective cortical regions. Moreover, we found that the OPA is also sensitive to such changes, while the RSC is tolerant to such changes. Thus, the geometric information typically associated with object recognition is also used during some aspects of scene processing. These findings provide evidence that scene-selective cortex differentially represents the geometric properties guiding navigation versus scene categorization. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Cognitive training and selective attention in the aging brain: an electrophysiological study.

    Science.gov (United States)

    O'Brien, Jennifer L; Edwards, Jerri D; Maxfield, Nathan D; Peronto, Carol L; Williams, Victoria A; Lister, Jennifer J

    2013-11-01

    Age-related deficits in selective attention are hypothesized to result from decrements in inhibition of task-irrelevant information. Speed of processing (SOP) training is an adaptive cognitive intervention designed to enhance processing speed for attention tasks. The effectiveness of SOP training to improve cognitive and everyday functional performance is well documented. However, underlying mechanisms of these training benefits are unknown. Participants completed a visual search task evaluated using event-related potentials (ERPs) before and after 10 weeks of SOP training or no contact. N2pc and P3b components were evaluated to determine SOP training effects on attentional resource allocation and capacity. Selective attention to a target was enhanced after SOP training compared to no training. N2pc and P3b amplitudes increased after training, reflecting attentional allocation and capacity enhancement, consistent with previous studies demonstrating behavioral improvements in selective attention following SOP training. Changes in ERPs related to attention allocation and capacity following SOP training support the idea that training leads to cognitive enhancement. Specifically, we provide electrophysiological evidence that SOP training may be successful in counteracting age-related declines in selective attention. This study provides important evidence of the underlying mechanisms by which SOP training improves cognitive function in older adults. Published by Elsevier Ireland Ltd.

  6. Prognostic factors in brain metastases: should patients be selected for aggressive treatment according to recursive partitioning analysis (RPA) classes?

    International Nuclear Information System (INIS)

    Nieder, Carsten; Nestle, Ursula; Motaref, Babak; Walter, Karin; Niewald, Marcus; Schnabel, Klaus

    2000-01-01

    Purpose: To determine whether or not Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) derived prognostic classes for patients with brain metastases are generally applicable and can be recommended as rational strategy for patient selection for future clinical trials. Inclusion of time to non-CNS death as additional endpoint besides death from any cause might result in further valuable information, as survival limitation due to uncontrolled extracranial disease can be explored. Methods: We performed a retrospective analysis of prognostic factors for survival and time to non-CNS death in 528 patients treated at a single institution with radiotherapy or surgery plus radiotherapy for brain metastases. For this purpose, patients were divided into groups with Karnofsky performance status (KPS) 0.05 for RPA class II versus III). However, it was 8.5 months in RPA class II patients with controlled primary tumor, which was found to be the only prognostic factor for time to non-CNS death in patients with KPS ≥70%. In patients with KPS <70%, no statistically significant prognostic factors were identified for this endpoint. Conclusions: Despite some differences, this analysis essentially confirmed the value of RPA-derived prognostic classes, as published by the RTOG, when survival was chosen as endpoint. RPA class I patients seem to be most likely to profit from aggressive treatment strategies and should be included in appropriate clinical trials. However, their number appears to be very limited. Considering time to non-CNS death, our results suggest that certain patients in RPA class II also might benefit from increased local control of brain metastases

  7. Selected Gray Matter Volumes and Gender but Not Basal Ganglia nor Cerebellum Gyri Discriminate Left Versus Right Cerebral Hemispheres: Multivariate Analyses in human Brains at 3T.

    Science.gov (United States)

    Roldan-Valadez, Ernesto; Suarez-May, Marcela A; Favila, Rafael; Aguilar-Castañeda, Erika; Rios, Camilo

    2015-07-01

    Interest in the lateralization of the human brain is evident through a multidisciplinary number of scientific studies. Understanding volumetric brain asymmetries allows the distinction between normal development stages and behavior, as well as brain diseases. We aimed to evaluate volumetric asymmetries in order to select the best gyri able to classify right- versus left cerebral hemispheres. A cross-sectional study performed in 47 right-handed young-adults healthy volunteers. SPM-based software performed brain segmentation, automatic labeling and volumetric analyses for 54 regions involving the cerebral lobes, basal ganglia and cerebellum from each cerebral hemisphere. Multivariate discriminant analysis (DA) allowed the assembling of a predictive model. DA revealed one discriminant function that significantly differentiated left vs. right cerebral hemispheres: Wilks' λ = 0.008, χ(2) (9) = 238.837, P brain gyri are able to accurately classify left vs. right cerebral hemispheres by using a multivariate approach; the selected regions correspond to key brain areas involved in attention, internal thought, vision and language; our findings favored the concept that lateralization has been evolutionary favored by mental processes increasing cognitive efficiency and brain capacity. © 2015 Wiley Periodicals, Inc.

  8. Region-selective effects of long-term lithium and carbamazepine administration on cyclic AMP levels in rat brain

    International Nuclear Information System (INIS)

    Wiborg, Ove; Krueger, Tanja; Jakosen, Soeren N.

    1999-01-01

    The effect of lithium and carbamazepine in the treatment of bipolar affective disorder is well established. Althougt a number of biochemical effects have been found, the exact molecular mechanisms underlying their therapeutic actions have not been elucidated nor are the target regions in the brain identified. Taken into account the important role of the cyclic AMP second messenger system in the regulation of neuronal exitability and the indications of its involvement in the pathophysiology of bipolar affective disorder, we have focused on the drug effects on cyclic AMP levels. The objectives of this investigation were to measure the effects on basal cyclic AMP levels, and to locate target regions within the rat brain after long-term administration of lithium and carbamazepine. Drug treatments were carried out for a period of 28 days. After either drug treatment the cyclic AMP level was increased 3-4 times in frontal cortex but unchanged in hippocampus, hypothalamus, thalamus, amygdala and in cerebellum. In neostratum the cyclic AMP level was decreased to about 30% after treatment with lithium. We suggest the common region-selective effect, observed for both drugs in frontal cortex, to be essential for the therapeutic actions of lithium and carbamazepine. (au)

  9. Region-selective effects of long-term lithium and carbamazepine administration on cyclic AMP levels in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Wiborg, Ove; Krueger, Tanja; Jakosen, Soeren N. [Psychiatric Hospital, Dept. of Biological Psychiatry, Risskov (Denmark)

    1999-02-01

    The effect of lithium and carbamazepine in the treatment of bipolar affective disorder is well established. Althougt a number of biochemical effects have been found, the exact molecular mechanisms underlying their therapeutic actions have not been elucidated nor are the target regions in the brain identified. Taken into account the important role of the cyclic AMP second messenger system in the regulation of neuronal exitability and the indications of its involvement in the pathophysiology of bipolar affective disorder, we have focused on the drug effects on cyclic AMP levels. The objectives of this investigation were to measure the effects on basal cyclic AMP levels, and to locate target regions within the rat brain after long-term administration of lithium and carbamazepine. Drug treatments were carried out for a period of 28 days. After either drug treatment the cyclic AMP level was increased 3-4 times in frontal cortex but unchanged in hippocampus, hypothalamus, thalamus, amygdala and in cerebellum. In neostratum the cyclic AMP level was decreased to about 30% after treatment with lithium. We suggest the common region-selective effect, observed for both drugs in frontal cortex, to be essential for the therapeutic actions of lithium and carbamazepine. (au) 46 refs.

  10. Neuropsychological profile of Parkinson's disease patients selected for deep brain stimulation surgery

    Directory of Open Access Journals (Sweden)

    Flavia Amaral Machado

    Full Text Available ABSTRACT Background: Parkinson's disease (PD shows symptoms involving motor and non-motor complications, including cognitive and behavioral changes, such changes might to contraindicate deep brain stimulation surgery (DBS. Objective: The aim of study was to investigate the neuropsychological profile of patients with PD in a waiting list for DBS. Methods: The neuropsychological evaluation was held in 30 patients of the ISCMPA Movement Disorders Clinic, with surgical indication based on the criteria of the responsible neurologists, in the period of 12 months. Instruments used: MMSE, FAB, MoCA, BDI, Semantic Verbal Fluency, PDQ-39, PDSS; and the UPDRS and Hoehn-Yahr scale. Results: The patients were mostly male (66.7% with a mean age of 59.37 (SD 10.60 and disease duration 9.33 (SD 4.08. There was cognitive impairment in 56.7% of patients by FAB and 76.7% by MoCA. Conclusion: Even in the earliest stages of the disease, there is the incidence of non-motor symptoms, especially in those subjects who had an early onset of the disease.

  11. Binary particle swarm optimization for frequency band selection in motor imagery based brain-computer interfaces.

    Science.gov (United States)

    Wei, Qingguo; Wei, Zhonghai

    2015-01-01

    A brain-computer interface (BCI) enables people suffering from affective neurological diseases to communicate with the external world. Common spatial pattern (CSP) is an effective algorithm for feature extraction in motor imagery based BCI systems. However, many studies have proved that the performance of CSP depends heavily on the frequency band of EEG signals used for the construction of covariance matrices. The use of different frequency bands to extract signal features may lead to different classification performances, which are determined by the discriminative and complementary information they contain. In this study, the broad frequency band (8-30 Hz) is divided into 10 sub-bands of band width 4 Hz and overlapping 2 Hz. Binary particle swarm optimization (BPSO) is used to find the best sub-band set to improve the performance of CSP and subsequent classification. Experimental results demonstrate that the proposed method achieved an average improvement of 6.91% in cross-validation accuracy when compared to broad band CSP.

  12. Deep brain stimulation of the subthalamic nucleus modulates reward processing and action selection in Parkinson patients.

    Science.gov (United States)

    Wagenbreth, Caroline; Zaehle, Tino; Galazky, Imke; Voges, Jürgen; Guitart-Masip, Marc; Heinze, Hans-Jochen; Düzel, Emrah

    2015-06-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for motor impairments in Parkinson's disease (PD) but its effect on the motivational regulation of action control is still not fully understood. We investigated whether DBS of the STN influences the ability of PD patients to act for anticipated reward or loss, or whether DBS improves action execution independent of motivational valence. 16 PD patients (12 male, mean age = 58.5 ± 10.17 years) treated with bilateral STN-DBS and an age- and gender-matched group of healthy controls (HC) performed a go/no-go task whose contingencies explicitly decouple valence and action. Patients were tested with (ON) and without (OFF) active STN stimulation. For HC, there was a benefit in performing rewarded actions when compared to actions that avoided punishment. PD patients showed such a benefit reliably only when STN stimulation was ON. In fact, the relative behavioral benefit for go for reward over go to avoid losing was stronger in the PD patients under DBS ON than in HC. In PD patients, rather than generally improving motor functions independent of motivational valence, modulation of the STN by DBS improves action execution specifically when rewards are anticipated. Thus, STN-DBS establishes a reliable congruency between action and reward ("Pavlovian congruency") and remarkably enhances it over the level observed in HC.

  13. Selective intra-arterial administration of {sup 18}F-FDG to the rat brain - effects on hemispheric uptake

    Energy Technology Data Exchange (ETDEWEB)

    Arnberg, Fabian; Samen, Erik; Lundberg, Johan; Grafstroem, Jonas; Soederman, Michael; Stone-Elander, Sharon; Holmin, Staffan [Karolinska Institutet, Department of Clinical Neuroscience, Stockholm (Sweden); Karolinska University Hospital-Solna, Department of Neuroradiology, Stockholm (Sweden); Lu, Li [Karolinska University Hospital-Solna, KERIC, Stockholm (Sweden)

    2014-05-15

    The purpose of this study was to investigate the radioligand uptake and iodine contrast distribution in the intra- and extracranial circulation of the rat, after intra-arterial injections to the common carotid artery and different parts of the internal carotid artery. All animal experiments were carried out in accordance with Karolinska Institutet's guidelines and were approved by the local laboratory animal ethics committee. We used clinical neurointerventional systems to place microcatheters in the extra- or intracranial carotid artery of 15 Sprague-Dawley rats. Here, injection dynamics of iodine contrast was assessed using digital subtraction angiography. Maintaining the catheter position, the animals were placed in a micro PET and small-animal positron emission tomography (PET) was used to analyze injections [2-{sup 18}F]-2-fluoro-2-deoxy-d-glucose ({sup 18}F-FDG). Microcatheters had to be placed in the intracranial carotid artery (iICA) for the infusate to distribute to the brain. Selective injection via the iICA resulted in a 9-fold higher uptake of {sup 18}F-FDG in the injected hemisphere (p < 0.005) compared to both intravenous and more proximal carotid artery injections. Furthermore, selective injection gave a dramatically improved contrast between the brain and extracranial tissue. Intra-arterial injection increases the cerebral uptake of a radiotracer dramatically compared to systemic injection. This technique has potential applications for endovascular treatment of malignancies allowing intra-interventional modifications of injection strategy, based on information on tumor perfusion and risk to surrounding normal parenchyma. Furthermore the technique may increase diagnostic sensitivity and avoid problems due to peripheral pharmacological barriers and first passage metabolism of labile tracers. (orig.)

  14. Selective intra-arterial administration of 18F-FDG to the rat brain - effects on hemispheric uptake

    International Nuclear Information System (INIS)

    Arnberg, Fabian; Samen, Erik; Lundberg, Johan; Grafstroem, Jonas; Soederman, Michael; Stone-Elander, Sharon; Holmin, Staffan; Lu, Li

    2014-01-01

    The purpose of this study was to investigate the radioligand uptake and iodine contrast distribution in the intra- and extracranial circulation of the rat, after intra-arterial injections to the common carotid artery and different parts of the internal carotid artery. All animal experiments were carried out in accordance with Karolinska Institutet's guidelines and were approved by the local laboratory animal ethics committee. We used clinical neurointerventional systems to place microcatheters in the extra- or intracranial carotid artery of 15 Sprague-Dawley rats. Here, injection dynamics of iodine contrast was assessed using digital subtraction angiography. Maintaining the catheter position, the animals were placed in a micro PET and small-animal positron emission tomography (PET) was used to analyze injections [2- 18 F]-2-fluoro-2-deoxy-d-glucose ( 18 F-FDG). Microcatheters had to be placed in the intracranial carotid artery (iICA) for the infusate to distribute to the brain. Selective injection via the iICA resulted in a 9-fold higher uptake of 18 F-FDG in the injected hemisphere (p < 0.005) compared to both intravenous and more proximal carotid artery injections. Furthermore, selective injection gave a dramatically improved contrast between the brain and extracranial tissue. Intra-arterial injection increases the cerebral uptake of a radiotracer dramatically compared to systemic injection. This technique has potential applications for endovascular treatment of malignancies allowing intra-interventional modifications of injection strategy, based on information on tumor perfusion and risk to surrounding normal parenchyma. Furthermore the technique may increase diagnostic sensitivity and avoid problems due to peripheral pharmacological barriers and first passage metabolism of labile tracers. (orig.)

  15. Stress and Withdrawal from Chronic Ethanol Induce Selective Changes in Neuroimmune mRNAs in Differing Brain Sites

    Directory of Open Access Journals (Sweden)

    Darin J. Knapp

    2016-07-01

    Full Text Available Stress is a strong risk factor in alcoholic relapse and may exert effects that mimic aspects of chronic alcohol exposure on neurobiological systems. With the neuroimmune system becoming a prominent focus in the study of the neurobiological consequences of stress, as well as chronic alcohol exposure proving to be a valuable focus in this regard, the present study sought to compare the effects of stress and chronic ethanol exposure on induction of components of the neuroimmune system. Rats were exposed to either 1 h exposure to a mild stressor (restraint or exposure to withdrawal from 15 days of chronic alcohol exposure (i.e., withdrawal from chronic ethanol, WCE and assessed for neuroimmune mRNAs in brain. Restraint stress alone elevated chemokine (C–C motif ligand 2 (CCL2, interleukin-1-beta (IL-1β, tumor necrosis factor alpha (TNFα and toll-like receptor 4 (TLR4 mRNAs in the cerebral cortex within 4 h with a return to a control level by 24 h. These increases were not accompanied by an increase in corresponding proteins. Withdrawal from WCE also elevated cytokines, but did so to varying degrees across different cytokines and brain regions. In the cortex, stress and WCE induced CCL2, TNFα, IL-1β, and TLR4 mRNAs. In the hypothalamus, only WCE induced cytokines (CCL2 and IL-1β while in the hippocampus, WCE strongly induced CCL2 while stress and WCE induced IL-1β. In the amygdala, only WCE induced CCL2. Finally—based on the previously demonstrated role of corticotropin-releasing factor 1 (CRF1 receptor inhibition in blocking WCE-induced cytokine mRNAs—the CRF1 receptor antagonist CP154,526 was administered to a subgroup of stressed rats and found to be inactive against induction of CCL2, TNFα, or IL-1β mRNAs. These differential results suggest that stress and WCE manifest broad neuroimmune effects in brain depending on the cytokine and brain region, and that CRF inhibition may not be a relevant mechanism in non-alcohol exposed animals

  16. Rooibos Flavonoids Inhibit the Activity of Key Adrenal Steroidogenic Enzymes, Modulating Steroid Hormone Levels in H295R Cells

    Directory of Open Access Journals (Sweden)

    Lindie Schloms

    2014-03-01

    Full Text Available Major rooibos flavonoids—dihydrochalcones, aspalathin and nothofagin, flavones—orientin and vitexin, and a flavonol, rutin, were investigated to determine their influence on the activity of adrenal steroidogenic enzymes, 3β-hydroxysteroid dehydrogenase (3βHSD2 and cytochrome P450 (P450 enzymes, P450 17α-hydroxylase/17,20-lyase (CYP17A1, P450 21-hydroxylase (CYP21A2 and P450 11β-hydroxylase (CYP11B1. All the flavonoids inhibited 3βHSD2 and CYP17A1 significantly, while the inhibition of downstream enzymes, CYP21A2 and CYP11B1, was both substrate and flavonoid specific. The dihydrochalcones inhibited the activity of CYP21A2, but not that of CYP11B1. Although rutin, orientin and vitexin inhibited deoxycortisol conversion by CYP11B1 significantly, inhibition of deoxycorticosterone was <20%. These three flavonoids were unable to inhibit CYP21A2, with negligible inhibition of deoxycortisol biosynthesis only. Rooibos inhibited substrate conversion by CYP17A1 and CYP21A2, while the inhibition of other enzyme activities was <20%. In H295R cells, rutin had the greatest inhibitory effect on steroid production upon forskolin stimulation, reducing total steroid output 2.3-fold, while no effect was detected under basal conditions. Nothofagin and vitexin had a greater inhibitory effect on overall steroid production compared to aspalathin and orientin, respectively. The latter compounds contain two hydroxyl groups on the B ring, while nothofagin and vitexin contain a single hydroxyl group. In addition, all of the flavonoids are glycosylated, albeit at different positions—dihydrochalcones at C3' and flavones at C8 on ring A, while rutin, a larger molecule, has a rutinosyl moiety at C3 on ring C. Structural differences regarding the number and position of hydroxyl and glucose moieties as well as structural flexibility could indicate different mechanisms by which these flavonoids influence the activity of adrenal steroidogenic enzymes.

  17. Selective visual attention to drive cognitive brain machine interfaces: from concepts to neurofeedback and rehabilitation applications

    Directory of Open Access Journals (Sweden)

    Elaine eAstrand

    2014-08-01

    Full Text Available Brain Machine Interfaces (BMI using motor cortical activity to drive an external effector like a screen cursor or a robotic arm have seen enormous success and proven their great rehabilitation potential. An emerging parallel effort is now directed to BMIs controlled by endogenous cognitive activity, also called cognitive BMIs. While more challenging, this approach opens new dimensions to the rehabilitation of cognitive disorders. In the present work, we focus on BMIs driven by visuospatial attention signals and we provide a critical review of these studies in the light of the accumulated knowledge about the psychophysics, anatomy and neurophysiology of visual spatial attention. Importantly, we provide a unique comparative overview of the several studies, ranging from noninvasive to invasive human and non-human primates studies, that decode attention-related information from ongoing neuronal activity. We discuss these studies in the light of the challenges attention-driven cognitive BMIs have to face. In a second part of the review, we discuss past and current attention-based neurofeedback studies, describing both the covert effects of neurofeedback onto neuronal activity and its overt behavioral effects. Importantly, we compare neurofeedback studies based on the amplitude of cortical activity to studies based on the enhancement of cortical information content. Last, we discuss several lines of future research and applications for attention-driven cognitive BCIs, including the rehabilitation of cognitive deficits, restored communication in locked-in patients, and open-field applications for enhanced cognition in normal subjects. The core motivation of this work is the key idea that the improvement of current cognitive BMIs for therapeutic and open field applications needs to be grounded in a proper interdisciplinary understanding of the physiology of the cognitive function of interest, be it spatial attention, working memory or any other

  18. An in vitro and in vivo study of peptide-functionalized nanoparticles for brain targeting : The importance of selective blood–brain barrier uptake

    NARCIS (Netherlands)

    Bode, Gerard H.; Coué, G.M.J.P.C.; Freese, Christian; Pickl, Karin E.; Sanchez-Purrà, Maria; Albaiges, Berta; Borrós, Salvador; van Winden, Ewoud C.; Tziveleka, Leto Aikaterini; Sideratou, Zili; Engbersen, Johan F.J.; Singh, Smriti; Albrecht, Krystyna; Groll, Jürgen; Möller, Martin; Pötgens, Andy J.G.; Schmitz, Christoph; Fröhlich, Eleonore; Grandfils, Christian; Sinner, Frank M.; Kirkpatrick, C. James; Steinbusch, Harry W.M.; Frank, Hans Georg; Unger, Ronald E.; Martinez-Martinez, Pilar

    2017-01-01

    Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood–brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial

  19. An automatic fuzzy-based multi-temporal brain digital subtraction angiography image fusion algorithm using curvelet transform and content selection strategy.

    Science.gov (United States)

    Momeni, Saba; Pourghassem, Hossein

    2014-08-01

    Recently image fusion has prominent role in medical image processing and is useful to diagnose and treat many diseases. Digital subtraction angiography is one of the most applicable imaging to diagnose brain vascular diseases and radiosurgery of brain. This paper proposes an automatic fuzzy-based multi-temporal fusion algorithm for 2-D digital subtraction angiography images. In this algorithm, for blood vessel map extraction, the valuable frames of brain angiography video are automatically determined to form the digital subtraction angiography images based on a novel definition of vessel dispersion generated by injected contrast material. Our proposed fusion scheme contains different fusion methods for high and low frequency contents based on the coefficient characteristic of wrapping second generation of curvelet transform and a novel content selection strategy. Our proposed content selection strategy is defined based on sample correlation of the curvelet transform coefficients. In our proposed fuzzy-based fusion scheme, the selection of curvelet coefficients are optimized by applying weighted averaging and maximum selection rules for the high frequency coefficients. For low frequency coefficients, the maximum selection rule based on local energy criterion is applied to better visual perception. Our proposed fusion algorithm is evaluated on a perfect brain angiography image dataset consisting of one hundred 2-D internal carotid rotational angiography videos. The obtained results demonstrate the effectiveness and efficiency of our proposed fusion algorithm in comparison with common and basic fusion algorithms.

  20. Hippocampal brain-derived neurotrophic factor but not neurotrophin-3 increases more in mice selected for increased voluntary wheel running.

    Science.gov (United States)

    Johnson, R A; Rhodes, J S; Jeffrey, S L; Garland, T; Mitchell, G S

    2003-01-01

    Voluntary wheel running in rats increases hippocampal brain-derived neurotrophic factor (BDNF) expression, a neurochemical important for neuronal survival, differentiation, connectivity and synaptic plasticity. Here, we report the effects of wheel running on BDNF and neurotrophin-3 (NT-3) protein levels in normal control mice, and in mice selectively bred (25 generations) for increased voluntary wheel running. We hypothesized that increased voluntary wheel running in selected (S) mice would increase CNS BDNF and NT-3 protein levels more than in control (C) mice. Baseline hippocampal BDNF levels (mice housed without running wheels) were similar in S and C mice. Following seven nights of running, hippocampal BDNF increased significantly more in S versus C mice, and levels were correlated with distance run (considering C and S mice together). Spinal and cerebellar BDNF and hippocampal NT-3 levels were not significantly affected by wheel running in any group, but there was a small, positive correlation between spinal C3-C6 BDNF levels and distance run (considering C and S mice together). This is the first study to demonstrate that mice which choose to run more have greater elevations in hippocampal BDNF, suggesting enhanced potential for exercise-induced hippocampal neuroplasticity.

  1. Effects of early focal brain injury on memory for visuospatial patterns: selective deficits of global-local processing.

    Science.gov (United States)

    Stiles, Joan; Stern, Catherine; Appelbaum, Mark; Nass, Ruth; Trauner, Doris; Hesselink, John

    2008-01-01

    Selective deficits in visuospatial processing are present early in development among children with perinatal focal brain lesions (PL). Children with right hemisphere PL (RPL) are impaired in configural processing, while children with left hemisphere PL (LPL) are impaired in featural processing. Deficits associated with LPL are less pervasive than those observed with RPL, but this difference may reflect the structure of the tasks used for assessment. Many of the tasks used to date may place greater demands on configural processing, thus highlighting this deficit in the RPL group. This study employed a task designed to place comparable demands on configural and featural processing, providing the opportunity to obtain within-task evidence of differential deficit. Sixty-two 5- to 14-year-old children (19 RPL, 19 LPL, and 24 matched controls) reproduced from memory a series of hierarchical forms (large forms composed of small forms). Global- and local-level reproduction accuracy was scored. Controls were equally accurate on global- and local-level reproduction. Children with RPL were selectively impaired on global accuracy, and children with LPL on local accuracy, thus documenting a double dissociation in global-local processing.

  2. Classification effects of real and imaginary movement selective attention tasks on a P300-based brain-computer interface

    Science.gov (United States)

    Salvaris, Mathew; Sepulveda, Francisco

    2010-10-01

    Brain-computer interfaces (BCIs) rely on various electroencephalography methodologies that allow the user to convey their desired control to the machine. Common approaches include the use of event-related potentials (ERPs) such as the P300 and modulation of the beta and mu rhythms. All of these methods have their benefits and drawbacks. In this paper, three different selective attention tasks were tested in conjunction with a P300-based protocol (i.e. the standard counting of target stimuli as well as the conduction of real and imaginary movements in sync with the target stimuli). The three tasks were performed by a total of 10 participants, with the majority (7 out of 10) of the participants having never before participated in imaginary movement BCI experiments. Channels and methods used were optimized for the P300 ERP and no sensory-motor rhythms were explicitly used. The classifier used was a simple Fisher's linear discriminant. Results were encouraging, showing that on average the imaginary movement achieved a P300 versus No-P300 classification accuracy of 84.53%. In comparison, mental counting, the standard selective attention task used in previous studies, achieved 78.9% and real movement 90.3%. Furthermore, multiple trial classification results were recorded and compared, with real movement reaching 99.5% accuracy after four trials (12.8 s), imaginary movement reaching 99.5% accuracy after five trials (16 s) and counting reaching 98.2% accuracy after ten trials (32 s).

  3. In and out of control: brain mechanisms linking fluency of action selection to self-agency in patients with schizophrenia.

    Science.gov (United States)

    Voss, Martin; Chambon, Valérian; Wenke, Dorit; Kühn, Simone; Haggard, Patrick

    2017-08-01

    Sense of agency refers to the feeling of control over one's actions, and their consequences. It involves both predictive processes linked to action control, and retrospective 'sense-making' causal inferences. Schizophrenia has been associated with impaired predictive processing, but the underlying mechanisms that impair patients' sense of agency remain unclear. We introduce a new 'prospective' aspect of agency and show that subliminally priming an action not only influences response times, but also influences reported sense of agency over subsequent action outcomes. This effect of priming was associated with altered connectivity between frontal areas and the angular gyrus. The effects on response times and on frontal action selection mechanisms were similar in patients with schizophrenia and in healthy volunteers. However, patients showed no effects of priming on sense of agency, no priming-related activation of angular gyrus, and no priming-related changes in fronto-parietal connectivity. We suggest angular gyrus activation reflects the experiences of agency, or non-agency, in part by processing action selection signals generated in the frontal lobes. The altered action awareness that characterizes schizophrenia may be due to impaired communication between these areas. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Fundulus heteroclitus gonadotropins.5: Small scale chromatographic fractionation of pituitary extracts into components with different steroidogenic activities using homologous bioassays

    Directory of Open Access Journals (Sweden)

    Petrino Teresa R

    2004-03-01

    Full Text Available Abstract Fractionation and characterization of gonadotropins (GtH from Fundulus heteroclitus pituitary extracts were carried out using a biocompatible liquid chromatographic procedure (Pharmacia FPLC system. Chromatographic fractions were monitored for gonadotropic activities (induction of oocyte maturation and steroid production using homologous follicle bioassays in vitro. Size-exclusion chromatography eluted gonadotropic activity in one major protein peak (Mr ~ 30,000. Anion-exchange and hydrophobic-interaction chromatography (HIC yielded two distinct peaks of 17beta-estradiol (E2- and 17alpha-hydroxy,20beta-dihydroprogesterone (DHP-promoting activity with associated oocyte maturation. Two-dimensional chromatography (chromatofocusing followed by HIC resolved pituitary extracts into two active fractions; both induced E2 synthesis, but one was relatively poor in eliciting DHP and testosterone production. Thus, using homologous bioassays, at least two quantitatively different gonadotropic (steroidogenic activities: an E2-promoting gonadotropin (GtH I-like and a DHP-promoting gonadotropin (GtH II-like, which has a lower isoelectric point but greater hydrophobicity than the former, can be distinguished from F. heteroclitus pituitaries by a variety of chromatographic procedures. This study complements previous biochemical and molecular data in F. heteroclitus and substantiates the duality of GtH function in a multiple-spawning teleost.

  5. Modulation of Steroidogenic Pathway in Rat Granulosa Cells with Subclinical Cd Exposure and Insulin Resistance: An Impact on Female Fertility

    Directory of Open Access Journals (Sweden)

    Muskaan Belani

    2014-01-01

    Full Text Available Changes in lifestyle lead to insulin resistance (IR in females ultimately predisposing them towards infertility. In addition, cadmium (Cd, an environmental endocrine disruptor, is reported for detrimental effects on granulosa cells, thus leading to ovarian dysfunction. A combination of these factors, lifestyle and environment, seems to play a role in etiology of idiopathic infertility that accounts for 50% amongst the total infertility cases. To address this issue, we made an attempt to investigate the extent of Cd impact on insulin-resistant (IR granulosa cells. We exposed adult female Charles Foster rats to dexamethasone and confirmed IR condition by fasting insulin resistance index (FIRI. On treatment of IR rats with Cd, the preliminary studies demonstrated prolonged estrous cyclicity, decrease in serum estradiol concentrations, abnormal histology of ovary, and increased granulosa cell death. Further gene and protein expression studies of steroidogenic acute regulatory (StAR protein, 17β-hydroxysteroid dehydrogenase (17β-HSD, and cytochrome P450 aromatase (CYP19A1 were performed. Protein expression studies demonstrated significant decrease in treated groups when compared with control. Study revealed that, in spite of the molecular parameters being affected at varied level, overall ovarian physiology is maximally affected in IR and Cd coexposed group, thus mimicking the condition similar to those prevailing in infertile females.

  6. Non-invasive brain stimulation targeting the right fusiform gyrus selectively increases working memory for faces.

    Science.gov (United States)

    Brunyé, Tad T; Moran, Joseph M; Holmes, Amanda; Mahoney, Caroline R; Taylor, Holly A

    2017-04-01

    The human extrastriate cortex contains a region critically involved in face detection and memory, the right fusiform gyrus. The present study evaluated whether transcranial direct current stimulation (tDCS) targeting this anatomical region would selectively influence memory for faces versus non-face objects (houses). Anodal tDCS targeted the right fusiform gyrus (Brodmann's Area 37), with the anode at electrode site PO10, and cathode at FP2. Two stimulation conditions were compared in a repeated-measures design: 0.5mA versus 1.5mA intensity; a separate control group received no stimulation. Participants completed a working memory task for face and house stimuli, varying in memory load from 1 to 4 items. Individual differences measures assessed trait-based differences in facial recognition skills. Results showed 1.5mA intensity stimulation (versus 0.5mA and control) increased performance at high memory loads, but only with faces. Lower overall working memory capacity predicted a positive impact of tDCS. Results provide support for the notion of functional specialization of the right fusiform regions for maintaining face (but not non-face object) stimuli in working memory, and further suggest that low intensity electrical stimulation of this region may enhance demanding face working memory performance particularly in those with relatively poor baseline working memory skills. Published by Elsevier Inc.

  7. [Research on K-means clustering segmentation method for MRI brain image based on selecting multi-peaks in gray histogram].

    Science.gov (United States)

    Chen, Zhaoxue; Yu, Haizhong; Chen, Hao

    2013-12-01

    To solve the problem of traditional K-means clustering in which initial clustering centers are selected randomly, we proposed a new K-means segmentation algorithm based on robustly selecting 'peaks' standing for White Matter, Gray Matter and Cerebrospinal Fluid in multi-peaks gray histogram of MRI brain image. The new algorithm takes gray value of selected histogram 'peaks' as the initial K-means clustering center and can segment the MRI brain image into three parts of tissue more effectively, accurately, steadily and successfully. Massive experiments have proved that the proposed algorithm can overcome many shortcomings caused by traditional K-means clustering method such as low efficiency, veracity, robustness and time consuming. The histogram 'peak' selecting idea of the proposed segmentootion method is of more universal availability.

  8. Quantification of Transporter and Receptor Proteins in Dog Brain Capillaries and Choroid Plexus: Relevance for the Distribution in Brain and CSF of Selected BCRP and P-gp Substrates.

    Science.gov (United States)

    Braun, Clemens; Sakamoto, Atsushi; Fuchs, Holger; Ishiguro, Naoki; Suzuki, Shinobu; Cui, Yunhai; Klinder, Klaus; Watanabe, Michitoshi; Terasaki, Tetsuya; Sauer, Achim

    2017-10-02

    Transporters at the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) play a pivotal role as gatekeepers for efflux or uptake of endogenous and exogenous molecules. The protein expression of a number of them has already been determined in the brains of rodents, nonhuman primates, and humans using quantitative targeted absolute proteomics (QTAP). The dog is an important animal model for drug discovery and development, especially for safety evaluations. The purpose of the present study was to clarify the relevance of the transporter protein expression for drug distribution in the dog brain and CSF. We used QTAP to examine the protein expression of 17 selected transporters and receptors at the dog BBB and BCSFB. For the first time, we directly linked the expression of two efflux transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), to regional brain and CSF distribution using specific substrates. Two cocktails, each containing one P-gp substrate (quinidine or apafant) and one BCRP substrate (dantrolene or daidzein) were infused intravenously prior to collection of the brain. Transporter expression varied only slightly between the capillaries of different brain regions and did not result in region-specific distribution of the investigated substrates. There were, however, distinct differences between brain capillaries and choroid plexus. Largest differences were observed for BCRP and P-gp: both were highly expressed in brain capillaries, but no BCRP and only low amounts of P-gp were detected in the choroid plexus. K p,uu,brain and K p,uu,CSF of both P-gp substrates were indicative of drug efflux. Also, K p,uu,brain for the BCRP substrates was low. In contrast, K p,uu,CSF for both BCRP substrates was close to unity, resulting in K p,uu,CSF /K p,uu,brain ratios of 7 and 8, respectively. We conclude that the drug transporter expression profiles differ between the BBB and BCSFB in dogs, that there are species differences

  9. Inhibiting mitochondrial β-oxidation selectively reduces levels of nonenzymatic oxidative polyunsaturated fatty acid metabolites in the brain.

    Science.gov (United States)

    Chen, Chuck T; Trépanier, Marc-Olivier; Hopperton, Kathryn E; Domenichiello, Anthony F; Masoodi, Mojgan; Bazinet, Richard P

    2014-03-01

    Schönfeld and Reiser recently hypothesized that fatty acid β-oxidation is a source of oxidative stress in the brain. To test this hypothesis, we inhibited brain mitochondrial β-oxidation with methyl palmoxirate (MEP) and measured oxidative polyunsaturated fatty acid (PUFA) metabolites in the rat brain. Upon MEP treatment, levels of several nonenzymatic auto-oxidative PUFA metabolites were reduced with few effects on enzymatically derived metabolites. Our finding confirms the hypothesis that reduced fatty acid β-oxidation decreases oxidative stress in the brain and β-oxidation inhibitors may be a novel therapeutic approach for brain disorders associated with oxidative stress.

  10. Effect of Brain Drain (Human Capital Flight of Librarians on Service Delivery in Some Selected Nigerian Universities

    Directory of Open Access Journals (Sweden)

    Clara Chinyere Okoro

    2014-06-01

    Full Text Available This study seeks to describe and analyze the challenges occasioned by brain drain or human capital flight of librarians on service delivery in Nigerian Universities. The research adopted a descriptive survey design. A purposive sampling technique was used to select two geopolitical zones (South-South and South-West from the six geopolitical zones of Nigeria. Total enumeration was used because the population under study was considered appropriate for the research. The instrument used for data collection was questionnaire. Sixty copies of the instrument were distributed to 60 librarians in the two selected geopolitical zones. Copies of all the questionnaires were completed, retrieved, and found usable, thus giving a response rate of 100%. Survey results indicated that 315 librarians emigrated to foreign lands for various reasons, including unstable academic calendar and prospects for further training among others. This loss of personnel in the university libraries has a negative impact on service delivery as qualified information professionals and Information and Communication Technology (ICT experts are limited to mentor the younger professionals. Shift duties in academic libraries are also scaled down for lack of manpower. Based on the findings, the researchers recommend that the Federal Government of Nigeria should, as a matter of urgency, robustly fund tertiary education to enhance productivity. As they do this, the National Universities Commission (NUC is to empower academic libraries by ensuring that the staff development policy is strictly adhered to. This will translate into self-enhancement for staff, positive job attitude, and retention of professionals in the system.

  11. An anti-steroidogenic inhibitory primer pheromone in male sea lamprey (Petromyzon marinus)

    Science.gov (United States)

    Chung-Davidson, Yu-Wen; Wang, Huiyong; Bryan, Mara B.; Wu, Hong; Johnson, Nicholas S.; Li, Weiming

    2013-01-01

    Reproductive functions can be modulated by both stimulatory and inhibitory primer pheromones released by conspecifics. Many stimulatory primer pheromones have been documented, but relatively few inhibitory primer pheromones have been reported in vertebrates. The sea lamprey male sex pheromone system presents an advantageous model to explore the stimulatory and inhibitory primer pheromone functions in vertebrates since several pheromone components have been identified. We hypothesized that a candidate sex pheromone component, 7α, 12α-dihydroxy-5α-cholan-3-one-24-oic acid (3 keto-allocholic acid or 3kACA), exerts priming effects through the hypothalamic-pituitary-gonadal (HPG) axis. To test this hypothesis, we measured the peptide concentrations and gene expressions of lamprey gonadotropin releasing hormones (lGnRH) and the HPG output in immature male sea lamprey exposed to waterborne 3kACA. Exposure to waterborne 3kACA altered neuronal activation markers such as jun and jun N-terminal kinase (JNK), and lGnRH mRNA levels in the brain. Waterborne 3kACA also increased lGnRH-III, but not lGnRH-I or -II, in the forebrain. In the plasma, 3kACA exposure decreased all three lGnRH peptide concentrations after 1 h exposure. After 2 h exposure, 3kACA increased lGnRHI and -III, but decreased lGnRH-II peptide concentrations in the plasma. Plasma lGnRH peptide concentrations showed differential phasic patterns. Group housing condition appeared to increase the averaged plasma lGnRH levels in male sea lamprey compared to isolated males. Interestingly, 15α-hydroxyprogesterone (15α-P) concentrations decreased after prolonged 3kACA exposure (at least 24 h). To our knowledge, this is the only known synthetic vertebrate pheromone component that inhibits steroidogenesis in males.

  12. Non-Invasive Brain Stimulation to Enhance Upper Limb Motor Practice Poststroke: A Model for Selection of Cortical Site

    Directory of Open Access Journals (Sweden)

    Michelle L. Harris-Love

    2017-05-01

    Full Text Available Motor practice is an essential part of upper limb motor recovery following stroke. To be effective, it must be intensive with a high number of repetitions. Despite the time and effort required, gains made from practice alone are often relatively limited, and substantial residual impairment remains. Using non-invasive brain stimulation to modulate cortical excitability prior to practice could enhance the effects of practice and provide greater returns on the investment of time and effort. However, determining which cortical area to target is not trivial. The implications of relevant conceptual frameworks such as Interhemispheric Competition and Bimodal Balance Recovery are discussed. In addition, we introduce the STAC (Structural reserve, Task Attributes, Connectivity framework, which incorporates patient-, site-, and task-specific factors. An example is provided of how this framework can assist in selecting a cortical region to target for priming prior to reaching practice poststroke. We suggest that this expanded patient-, site-, and task-specific approach provides a useful model for guiding the development of more successful approaches to neuromodulation for enhancing motor recovery after stroke.

  13. Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds

    International Nuclear Information System (INIS)

    Gracia, Tannia; Hilscherova, Klara; Jones, Paul D.; Newsted, John L.; Higley, Eric B.; Zhang, Xiaowei; Hecker, Markus; Murphy, Margaret B.; Yu, Richard M.K.; Lam, Paul K.S.; Wu, Rudolf S.S.; Giesy, John P.

    2007-01-01

    The H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3βHSD2, CYP11β1, CYP11β2, CYP17 and CYP19, was quantified by Q-RT-PCR. Production of the steroid hormones estradiol (E2), testosterone (T) and progesterone (P) was also evaluated. Antibiotics were shown to modulate gene expression and hormone production. Amoxicillin up-regulated the expression of CYP11β2 and CYP19 by more than 2-fold and induced estradiol production up to almost 3-fold. Erythromycin significantly increased CYP11β2 expression and the production of P and E2 by 3.5- and 2.4-fold, respectively, while production of T was significantly decreased. The β-blocker salbutamol caused the greatest induction of CYP17, more than 13-fold, and significantly decreased E2 production. The binary mixture of cyproterone and salbutamol significantly down-regulated expression of CYP19, while a mixture of ethynylestradiol and trenbolone, increased E2 production 3.7-fold. Estradiol production was significantly affected by changes in concentrations of trenbolone, cyproterone, and ethynylestradiol. Exposures with individual pharmaceuticals showed the possible secondary effects that drugs may exert on steroid production. Results from binary mixture exposures suggested the possible type of interactions that may occur between drugs and the joint effects product of such interactions. Dose-response results indicated that although two chemicals may share a common mechanism of action the concentration effects observed may be significantly different

  14. Effects of methomyl on steroidogenic gene transcription of the hypothalamic-pituitary-gonad-liver axis in male tilapia.

    Science.gov (United States)

    Meng, ShunLong; Qiu, LiPing; Hu, GengDong; Fan, LiMin; Song, Chao; Zheng, Yao; Wu, Wei; Qu, JianHong; Li, DanDan; Chen, JiaZhang; Xu, Pao

    2016-12-01

    Male tilapia were exposed to sub-lethal methomyl concentrations of 0, 0.2, 2, 20 or 200 μg/L for 30 d, and were subsequently cultured in methomyl-free water for 18 d. Relative transcript abundance of steroidogenic genes involved in the HPGL axis of male tilapia was examined at 30 d in the exposure test and at 18 d in the recovery test. The results revealed that low concentrations of methomyl (0.2 and 2 μg/L) did not cause significant changes in gene mRNA levels in the HPGL axis of male tilapia; thus, we considered 2 μg/L concentrations as the level that showed no apparent adverse endocrine disruption effects. However, higher concentrations of methomyl (20 and 200 μg/L) disrupted the endocrine system and caused significant increase in the levels of GnRH2, GnRH3, ERα, and ERβ genes in the hypothalamus, GnRHR and FSHβ genes in the pituitary, CYP19a, FSHR, and ERα genes in the testis, and VTG and ERα genes in the liver, and significantly decreased the levels of LHR, StAR, 3β-HSD, and ARα genes in the testis and LHβ gene in the pituitary, leading to changes in sex steroid hormone and vitellogenin levels in the serum and ultimately resulting in reproductive dysfunction in male tilapia. The recovery tests showed that the toxicity effect caused by 20 μg/L methomyl was reversible; however, the toxicity effect at 200 μg/L of methomyl was irreversible after 18 d. Therefore, we concluded that 200 μg/L was the threshold concentration for methomyl-induced irreversible endocrine disruption in male tilapia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Characterization of novel StAR (steroidogenic acute regulatory protein mutations causing non-classic lipoid adrenal hyperplasia.

    Directory of Open Access Journals (Sweden)

    Christa E Flück

    Full Text Available CONTEXT: Steroidogenic acute regulatory protein (StAR is crucial for transport of cholesterol to mitochondria where biosynthesis of steroids is initiated. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH. OBJECTIVE: StAR gene mutations causing partial loss of function manifest atypical and may be mistaken as familial glucocorticoid deficiency. Only a few mutations have been reported. DESIGN: To report clinical, biochemical, genetic, protein structure and functional data on two novel StAR mutations, and to compare them with published literature. SETTING: Collaboration between the University Children's Hospital Bern, Switzerland, and the CIBERER, Hospital Vall d'Hebron, Autonomous University, Barcelona, Spain. PATIENTS: Two subjects of a non-consanguineous Caucasian family were studied. The 46,XX phenotypic normal female was diagnosed with adrenal insufficiency at the age of 10 months, had normal pubertal development and still has no signs of hypergonodatropic hypogonadism at 32 years of age. Her 46,XY brother was born with normal male external genitalia and was diagnosed with adrenal insufficiency at 14 months. Puberty was normal and no signs of hypergonadotropic hypogonadism are present at 29 years of age. RESULTS: StAR gene analysis revealed two novel compound heterozygote mutations T44HfsX3 and G221S. T44HfsX3 is a loss-of-function StAR mutation. G221S retains partial activity (∼30% and is therefore responsible for a milder, non-classic phenotype. G221S is located in the cholesterol binding pocket and seems to alter binding/release of cholesterol. CONCLUSIONS: StAR mutations located in the cholesterol binding pocket (V187M, R188C, R192C, G221D/S seem to cause non-classic lipoid CAH. Accuracy of genotype-phenotype prediction by in vitro testing may vary with the assays employed.

  16. Patients with primary biliary cholangitis and fatigue present with depressive symptoms and selected cognitive deficits, but with normal attention performance and brain structure.

    Science.gov (United States)

    Zenouzi, Roman; von der Gablentz, Janina; Heldmann, Marcus; Göttlich, Martin; Weiler-Normann, Christina; Sebode, Marcial; Ehlken, Hanno; Hartl, Johannes; Fellbrich, Anja; Siemonsen, Susanne; Schramm, Christoph; Münte, Thomas F; Lohse, Ansgar W

    2018-01-01

    In primary biliary cholangitis (PBC) fatigue is a major clinical challenge of unknown etiology. By demonstrating that fatigue in PBC is associated with an impaired cognitive performance, previous studies have pointed out the possibility of brain abnormalities underlying fatigue in PBC. Whether structural brain changes are present in PBC patients with fatigue, however, is unclear. To evaluate the role of structural brain abnormalities in PBC patients severely affected from fatigue we, therefore, performed a case-control cerebral magnetic resonance imaging (cMRI) study and correlated changes of white and grey brain matter with the cognitive and attention performance. 20 female patients with PBC and 20 female age-matched controls were examined in this study. The assessment of fatigue, psychological symptoms, cognitive and attention performance included clinical questionnaires, established cognition tests and a computerized test battery of attention performance. T1-weighted cMRI and diffusion tensor imaging (DTI) scans were acquired with a 3 Tesla scanner. Structural brain alterations were investigated with voxel-based morphometry (VBM) and DTI analyses. Results were correlated to the cognitive and attention performance. Compared to healthy controls, PBC patients had significantly higher levels of fatigue and associated psychological symptoms. Except for an impairment of verbal fluency, no cognitive or attention deficits were found in the PBC cohort. The VBM and DTI analyses revealed neither major structural brain abnormalities in the PBC cohort nor correlations with the cognitive and attention performance. Despite the high burden of fatigue and selected cognitive deficits, the attention performance of PBC patients appears to be comparable to healthy people. As structural brain alterations do not seem to be present in PBC patients with fatigue, fatigue in PBC must be regarded as purely functional. Future studies should evaluate, whether functional brain changes

  17. Patients with primary biliary cholangitis and fatigue present with depressive symptoms and selected cognitive deficits, but with normal attention performance and brain structure.

    Directory of Open Access Journals (Sweden)

    Roman Zenouzi

    Full Text Available In primary biliary cholangitis (PBC fatigue is a major clinical challenge of unknown etiology. By demonstrating that fatigue in PBC is associated with an impaired cognitive performance, previous studies have pointed out the possibility of brain abnormalities underlying fatigue in PBC. Whether structural brain changes are present in PBC patients with fatigue, however, is unclear. To evaluate the role of structural brain abnormalities in PBC patients severely affected from fatigue we, therefore, performed a case-control cerebral magnetic resonance imaging (cMRI study and correlated changes of white and grey brain matter with the cognitive and attention performance.20 female patients with PBC and 20 female age-matched controls were examined in this study. The assessment of fatigue, psychological symptoms, cognitive and attention performance included clinical questionnaires, established cognition tests and a computerized test battery of attention performance. T1-weighted cMRI and diffusion tensor imaging (DTI scans were acquired with a 3 Tesla scanner. Structural brain alterations were investigated with voxel-based morphometry (VBM and DTI analyses. Results were correlated to the cognitive and attention performance.Compared to healthy controls, PBC patients had significantly higher levels of fatigue and associated psychological symptoms. Except for an impairment of verbal fluency, no cognitive or attention deficits were found in the PBC cohort. The VBM and DTI analyses revealed neither major structural brain abnormalities in the PBC cohort nor correlations with the cognitive and attention performance.Despite the high burden of fatigue and selected cognitive deficits, the attention performance of PBC patients appears to be comparable to healthy people. As structural brain alterations do not seem to be present in PBC patients with fatigue, fatigue in PBC must be regarded as purely functional. Future studies should evaluate, whether functional brain

  18. C/EBPβ (CCAAT/enhancer-binding protein β) mediates progesterone production through transcriptional regulation in co-operation with SF-1 (steroidogenic factor-1).

    Science.gov (United States)

    Mizutani, Tetsuya; Ju, Yunfeng; Imamichi, Yoshitaka; Osaki, Tsukasa; Yazawa, Takashi; Kawabe, Shinya; Ishikane, Shin; Matsumura, Takehiro; Kanno, Masafumi; Kamiki, Yasue; Kimura, Kohei; Minamino, Naoto; Miyamoto, Kaoru

    2014-06-15

    The transcription factor SF-1 (steroidogenic factor-1) is a master regulator of steroidogenesis. Previously, we have found that SF-1 induces the differentiation of mesenchymal stem cells into steroidogenic cells. To elucidate the molecular mechanisms of SF-1-mediated functions, we attempted to identify protein components of the SF-1 nuclear protein complex in differentiated cells. SF-1 immunoaffinity chromatography followed by MS/MS analysis was performed, and 24 proteins were identified. Among these proteins, we focused on C/EBPβ (CCAAT/enhancer-binding protein β), which is an essential transcription factor for ovulation and luteinization, as the transcriptional mechanisms of C/EBPβ working together with SF-1 are poorly understood. C/EBPβ knockdown attenuated cAMP-induced progesterone production in granulosa tumour-derived KGN cells by altering STAR (steroidogenic acute regulatory protein), CYP11A1 (cytochrome P450, family 11, subfamily A, polypeptide 1) and HSD3B2 (hydroxy-δ-5-steroid dehydrogenase, 3β- and steroid δ-isomerase 2) expression. EMSA and ChIP assays revealed novel C/EBPβ-binding sites in the upstream regions of the HSD3B2 and CYP11A1 genes. These interactions were enhanced by cAMP stimulation. Luciferase assays showed that C/EBPβ-responsive regions were found in each promoter and C/EBPβ is involved in the cAMP-induced transcriptional activity of these genes together with SF-1. These results indicate that C/EBPβ is an important mediator of progesterone production by working together with SF-1, especially under tropic hormone-stimulated conditions.

  19. Nasonia Parasitic Wasps Escape from Haller's Rule by Diphasic, Partially Isometric Brain-Body Size Scaling and Selective Neuropil Adaptations

    NARCIS (Netherlands)

    Groothuis, Jitte; Smid, Hans M.

    2017-01-01

    Haller's rule states that brains scale allometrically with body size in all animals, meaning that relative brain size increases with decreasing body size. This rule applies both on inter- and intraspecific comparisons. Only 1 species, the extremely small parasitic wasp Trichogramma evanescens, is

  20. Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice.

    Science.gov (United States)

    Michinaga, Shotaro; Nagase, Marina; Matsuyama, Emi; Yamanaka, Daisuke; Seno, Naoki; Fuka, Mayu; Yamamoto, Yui; Koyama, Yutaka

    2014-01-01

    Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs) are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice). Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV) administration of BQ788 (ETB antagonist), IRL-2500 (ETB antagonist), or FR139317 (ETA antagonist) prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults.

  1. Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice.

    Directory of Open Access Journals (Sweden)

    Shotaro Michinaga

    Full Text Available Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice. Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV administration of BQ788 (ETB antagonist, IRL-2500 (ETB antagonist, or FR139317 (ETA antagonist prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults.

  2. Dioxin exposure reduces the steroidogenic capacity of mouse antral follicles mainly at the level of HSD17B1 without altering atresia

    Energy Technology Data Exchange (ETDEWEB)

    Karman, Bethany N., E-mail: bklement@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbshivapur@gmail.com; Hannon, Patrick, E-mail: phannon2@illinois.edu; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2012-10-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent ovarian toxicant. Previously, we demonstrated that in vitro TCDD (1 nM) exposure decreases production/secretion of the sex steroid hormones progesterone (P4), androstenedione (A4), testosterone (T), and 17β-estradiol (E2) in mouse antral follicles. The purpose of this study was to determine the mechanism by which TCDD inhibits steroidogenesis. Specifically, we examined the effects of TCDD on the steroidogenic enzymes, atresia, and the aryl hydrocarbon receptor (AHR) protein. TCDD exposure for 48 h increased levels of A4, without changing HSD3B1 protein, HSD17B1 protein, estrone (E1), T or E2 levels. Further, TCDD did not alter atresia ratings compared to vehicle at 48 h. TCDD, however, did down regulate the AHR protein at 48 h. TCDD exposure for 96 h decreased transcript levels for Cyp11a1, Cyp17a1, Hsd17b1, and Cyp19a1, but increased Hsd3b1 transcript. TCDD exposure particularly lowered both Hsd17b1 transcript and HSD17B1 protein. However, TCDD exposure did not affect levels of E1 in the media nor atresia ratings at 96 h. TCDD, however, decreased levels of the proapoptotic factor Bax. Collectively, these data suggest that TCDD exposure causes a major block in the steroidogenic enzyme conversion of A4 to T and E1 to E2 and that it regulates apoptotic pathways, favoring survival over death in antral follicles. Finally, the down‐regulation of the AHR protein in TCDD exposed follicles persisted at 96 h, indicating that the activation and proteasomal degradation of this receptor likely plays a central role in the impaired steroidogenic capacity and altered apoptotic pathway of exposed antral follicles. -- Highlights: ► TCDD disrupts steroidogenic enzymes in mouse antral follicles. ► TCDD particularly affects the HSD17B1 enzyme in mouse antral follicles. ► TCDD does not affect atresia ratings in mouse antral follicles. ► TCDD decreases levels of the proapoptitic factor Bax in mouse antral follicles.

  3. (-)1-(Benzofuran-2-yl)-2-propylaminopentane, [(-)BPAP], a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain.

    Science.gov (United States)

    Knoll, J; Yoneda, F; Knoll, B; Ohde, H; Miklya, I

    1999-12-01

    1. The brain constituents beta-phenylethylamine (PEA) and tryptamine enhance the impulse propagation mediated transmitter release (exocytosis) from the catecholaminergic and serotoninergic neurons in the brain ('catecholaminergic/serotoninergic activity enhancer, CAE/SAE, effect'). (-)Deprenyl (Selegiline) and (-)1-phenyl-2-propylaminopentane [(-)PPAP] are amphetamine derived CAE substances devoid of the catecholamine releasing property. 2. By changing the aromatic ring in PPAP we developed highly potent and selective CAE/SAE substances, structurally unrelated to the amphetamines. Out of 65 newly synthetized compounds, a tryptamine derived structure, (-)1-(benzofuran-2-yl)-2-propylaminopentane [(-)BPAP] was selected as a potential follower of (-)deprenyl in the clinic and as a reference compound for further analysis of the CAE/SAE mechanism in the mammalian brain. 3. (-)BPAP significantly enhanced in 0.18 micromol 1(-1) concentration the impulse propagation mediated release of [(3)H]-noradrenaline and [(3)H]-dopamine and in 36 nmol 1(-1) concentration the release of [(3)H]-serotonin from the isolated brain stem of rats. The amount of catecholamines and serotonin released from isolated discrete rat brain regions (dopamine from the striatum, substantia nigra and tuberculum olfactorium, noradrenaline from the locus coeruleus and serotonin from the raphe) enhanced significantly in the presence of 10(-12) - 10(-14) M (-)BPAP. BPAP protected cultured hippocampal neurons from the neurotoxic effect of beta-amyloid in 10(-14) M concentration. In rats (-)BPAP significantly enhanced the activity of the catecholaminergic and serotoninergic neurons in the brain 30 min after acute injection of 0.1 microg kg(-1) s.c. In the shuttle box, (-)BPAP in rats was about 130 times more potent than (-)deprenyl in antagonizing tetrabenazine induced inhibition of performance.

  4. (−)1-(Benzofuran-2-yl)-2-propylaminopentane, [(−)BPAP], a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain

    Science.gov (United States)

    Knoll, Joseph; Yoneda, Fumio; Knoll, Berta; Ohde, Hironori; Miklya, Ildikó

    1999-01-01

    The brain constituents β-phenylethylamine (PEA) and tryptamine enhance the impulse propagation mediated transmitter release (exocytosis) from the catecholaminergic and serotoninergic neurons in the brain (‘catecholaminergic/serotoninergic activity enhancer, CAE/SAE, effect'). (−)Deprenyl (Selegiline) and (−)1-phenyl-2-propylaminopentane [(−)PPAP] are amphetamine derived CAE substances devoid of the catecholamine releasing property.By changing the aromatic ring in PPAP we developed highly potent and selective CAE/SAE substances, structurally unrelated to the amphetamines. Out of 65 newly synthetized compounds, a tryptamine derived structure, (−)1-(benzofuran-2-yl)-2-propylaminopentane [(−)BPAP] was selected as a potential follower of (−)deprenyl in the clinic and as a reference compound for further analysis of the CAE/SAE mechanism in the mammalian brain.(−)BPAP significantly enhanced in 0.18 μmol 1−1 concentration the impulse propagation mediated release of [3H]-noradrenaline and [3H]-dopamine and in 36 nmol 1−1 concentration the release of [3H]-serotonin from the isolated brain stem of rats. The amount of catecholamines and serotonin released from isolated discrete rat brain regions (dopamine from the striatum, substantia nigra and tuberculum olfactorium, noradrenaline from the locus coeruleus and serotonin from the raphe) enhanced significantly in the presence of 10−12–10−14 M (−)BPAP. BPAP protected cultured hippocampal neurons from the neurotoxic effect of β-amyloid in 10−14 M concentration. In rats (−)BPAP significantly enhanced the activity of the catecholaminergic and serotoninergic neurons in the brain 30 min after acute injection of 0.1 μg kg−1 s.c. In the shuttle box, (−)BPAP in rats was about 130 times more potent than (−)deprenyl in antagonizing tetrabenazine induced inhibition of performance. PMID:10588928

  5. Target Selection Recommendations Based on Impact of Deep Brain Stimulation Surgeries on Nonmotor Symptoms of Parkinson′s Disease

    Directory of Open Access Journals (Sweden)

    Xiao-Hong Wang

    2015-01-01

    Full Text Available Objective: This review examines the evidence that deep brain stimulation (DBS has extensive impact on nonmotor symptoms (NMSs of patients with Parkinson′s disease (PD. Data Sources: We retrieved information from the PubMed database up to September, 2015, using various search terms and their combinations including PD, NMSs, DBS, globus pallidus internus (GPi, subthalamic nucleus (STN, and ventral intermediate thalamic nucleus. Study Selection: We included data from peer-reviewed journals on impacts of DBS on neuropsychological profiles, sensory function, autonomic symptoms, weight changes, and sleep disturbances. For psychological symptoms and cognitive impairment, we tried to use more reliable proofs: Random, control, multicenter, large sample sizes, and long period follow-up clinical studies. We categorized the NMSs into four groups: those that would improve definitively following DBS; those that are not significantly affected by DBS; those that remain controversial on their surgical benefit; and those that can be worsened by DBS. Results: In general, it seems to be an overall beneficial effect of DBS on NMSs, such as sensory, sleep, gastrointestinal, sweating, cardiovascular, odor, urological symptoms, and sexual dysfunction, GPi-DBS may produce similar results; Both STN and Gpi-DBS are safe with regard to cognition and psychology over long-term follow-up, though verbal fluency decline is related to DBS; The impact of DBS on behavioral addictions and dysphagia is still uncertain. Conclusions: As the motor effects of STN-DBS and GPi-DBS are similar, NMSs may determine the target choice in surgery of future patients.

  6. Presynaptic selectivity of a ligand for serotonin 1A receptors revealed by in vivo PET assays of rat brain.

    Directory of Open Access Journals (Sweden)

    Takeaki Saijo

    Full Text Available A novel investigational antidepressant with high affinity for the serotonin transporter and the serotonin 1A (5-HT(1A receptor, called Wf-516 (structural formula: (2S-1-[4-(3,4-dichlorophenylpiperidin-1-yl]-3-[2-(5-methyl-1,3,4-oxadiazol-2-ylbenzo[b]furan-4-yloxy]propan-2-ol monohydrochloride, has been found to exert a rapid therapeutic effect, although the mechanistic basis for this potential advantage remains undetermined. We comparatively investigated the pharmacokinetics and pharmacodynamics of Wf-516 and pindolol by positron emission tomographic (PET and autoradiographic assays of rat brains in order to elucidate their molecular interactions with presynaptic and postsynaptic 5-HT(1A receptors. In contrast to the full receptor occupancy by pindolol in PET measurements, the binding of Wf-516 to 5-HT(1A receptors displayed limited capacity, with relatively high receptor occupancy being achieved in regions predominantly containing presynaptic receptors. This selectivity was further proven by PET scans of neurotoxicant-treated rats deficient in presynaptic 5-HT(1A receptors. In addition, [(35S]guanosine 5'-O-[γ-thio]triphosphate autoradiography indicated a partial agonistic ability of Wf-516 for 5-HT(1A receptors. This finding has lent support to reports that diverse partial agonists for 5-HT(1A receptors exert high sensitivity for presynaptic components. Thus, the present PET data suggest a relatively high capacity of presynaptic binding sites for partial agonists. Since our in vitro and ex vivo autoradiographies failed to illustrate these distinct features of Wf-516, in vivo PET imaging is considered to be, thus far, the sole method capable of pharmacokinetically demonstrating the unique actions of Wf-516 and similar new-generation antidepressants.

  7. Presynaptic selectivity of a ligand for serotonin 1A receptors revealed by in vivo PET assays of rat brain.

    Science.gov (United States)

    Saijo, Takeaki; Maeda, Jun; Okauchi, Takashi; Maeda, Jun-ichi; Morio, Yasunori; Kuwahara, Yasuhiro; Suzuki, Masayuki; Goto, Nobuharu; Fukumura, Toshimitsu; Suhara, Tetsuya; Higuchi, Makoto

    2012-01-01

    A novel investigational antidepressant with high affinity for the serotonin transporter and the serotonin 1A (5-HT(1A)) receptor, called Wf-516 (structural formula: (2S)-1-[4-(3,4-dichlorophenyl)piperidin-1-yl]-3-[2-(5-methyl-1,3,4-oxadiazol-2-yl)benzo[b]furan-4-yloxy]propan-2-ol monohydrochloride), has been found to exert a rapid therapeutic effect, although the mechanistic basis for this potential advantage remains undetermined. We comparatively investigated the pharmacokinetics and pharmacodynamics of Wf-516 and pindolol by positron emission tomographic (PET) and autoradiographic assays of rat brains in order to elucidate their molecular interactions with presynaptic and postsynaptic 5-HT(1A) receptors. In contrast to the full receptor occupancy by pindolol in PET measurements, the binding of Wf-516 to 5-HT(1A) receptors displayed limited capacity, with relatively high receptor occupancy being achieved in regions predominantly containing presynaptic receptors. This selectivity was further proven by PET scans of neurotoxicant-treated rats deficient in presynaptic 5-HT(1A) receptors. In addition, [(35)S]guanosine 5'-O-[γ-thio]triphosphate autoradiography indicated a partial agonistic ability of Wf-516 for 5-HT(1A) receptors. This finding has lent support to reports that diverse partial agonists for 5-HT(1A) receptors exert high sensitivity for presynaptic components. Thus, the present PET data suggest a relatively high capacity of presynaptic binding sites for partial agonists. Since our in vitro and ex vivo autoradiographies failed to illustrate these distinct features of Wf-516, in vivo PET imaging is considered to be, thus far, the sole method capable of pharmacokinetically demonstrating the unique actions of Wf-516 and similar new-generation antidepressants.

  8. Diagnosing Autism Spectrum Disorder from Brain Resting-State Functional Connectivity Patterns Using a Deep Neural Network with a Novel Feature Selection Method.

    Science.gov (United States)

    Guo, Xinyu; Dominick, Kelli C; Minai, Ali A; Li, Hailong; Erickson, Craig A; Lu, Long J

    2017-01-01

    The whole-brain functional connectivity (FC) pattern obtained from resting-state functional magnetic resonance imaging data are commonly applied to study neuropsychiatric conditions such as autism spectrum disorder (ASD) by using different machine learning models. Recent studies indicate that both hyper- and hypo- aberrant ASD-associated FCs were widely distributed throughout the entire brain rather than only in some specific brain regions. Deep neural networks (DNN) with multiple hidden layers have shown the ability to systematically extract lower-to-higher level information from high dimensional data across a series of neural hidden layers, significantly improving classification accuracy for such data. In this study, a DNN with a novel feature selection method (DNN-FS) is developed for the high dimensional whole-brain resting-state FC pattern classification of ASD patients vs. typical development (TD) controls. The feature selection method is able to help the DNN generate low dimensional high-quality representations of the whole-brain FC patterns by selecting features with high discriminating power from multiple trained sparse auto-encoders. For the comparison, a DNN without the feature selection method (DNN-woFS) is developed, and both of them are tested with different architectures (i.e., with different numbers of hidden layers/nodes). Results show that the best classification accuracy of 86.36% is generated by the DNN-FS approach with 3 hidden layers and 150 hidden nodes (3/150). Remarkably, DNN-FS outperforms DNN-woFS for all architectures studied. The most significant accuracy improvement was 9.09% with the 3/150 architecture. The method also outperforms other feature selection methods, e.g., two sample t -test and elastic net. In addition to improving the classification accuracy, a Fisher's score-based biomarker identification method based on the DNN is also developed, and used to identify 32 FCs related to ASD. These FCs come from or cross different pre

  9. Diagnosing Autism Spectrum Disorder from Brain Resting-State Functional Connectivity Patterns Using a Deep Neural Network with a Novel Feature Selection Method

    Directory of Open Access Journals (Sweden)

    Xinyu Guo

    2017-08-01

    Full Text Available The whole-brain functional connectivity (FC pattern obtained from resting-state functional magnetic resonance imaging data are commonly applied to study neuropsychiatric conditions such as autism spectrum disorder (ASD by using different machine learning models. Recent studies indicate that both hyper- and hypo- aberrant ASD-associated FCs were widely distributed throughout the entire brain rather than only in some specific brain regions. Deep neural networks (DNN with multiple hidden layers have shown the ability to systematically extract lower-to-higher level information from high dimensional data across a series of neural hidden layers, significantly improving classification accuracy for such data. In this study, a DNN with a novel feature selection method (DNN-FS is developed for the high dimensional whole-brain resting-state FC pattern classification of ASD patients vs. typical development (TD controls. The feature selection method is able to help the DNN generate low dimensional high-quality representations of the whole-brain FC patterns by selecting features with high discriminating power from multiple trained sparse auto-encoders. For the comparison, a DNN without the feature selection method (DNN-woFS is developed, and both of them are tested with different architectures (i.e., with different numbers of hidden layers/nodes. Results show that the best classification accuracy of 86.36% is generated by the DNN-FS approach with 3 hidden layers and 150 hidden nodes (3/150. Remarkably, DNN-FS outperforms DNN-woFS for all architectures studied. The most significant accuracy improvement was 9.09% with the 3/150 architecture. The method also outperforms other feature selection methods, e.g., two sample t-test and elastic net. In addition to improving the classification accuracy, a Fisher's score-based biomarker identification method based on the DNN is also developed, and used to identify 32 FCs related to ASD. These FCs come from or cross

  10. Specific in vivo binding in the rat brain of [18F]RP 62203: A selective 5-HT2A receptor radioligand for positron emission tomography

    International Nuclear Information System (INIS)

    Besret, Laurent; Dauphin, Francois; Huard, Cecile; Lasne, Marie-Claire; Vivet, Richard; Mickala, Patrick; Barbelivien, Alexandra; Baron, Jean-Claude

    1996-01-01

    In vivo pharmacokinetic and brain binding characteristics of [ 18 F]RP 62203, a selective high-affinity serotonergic 5-HT 2A receptor antagonist, were assessed in the rat following intravenous injection of trace amount of the radioligand. The radioactive distribution profile observed in the brain 60 min after injection was characterized by greater than fourfold higher uptake in neocortex as compared to cerebellum (0.38 ± 0.07% injected dose/g, % ID/g and 0.08 ± 0.01 ID/g, respectively), consistent with in vivo specific binding to the 5-HT 2A receptor. Furthermore, specific [ 18 F]RP 62203 binding significantly correlated with the reported in vitro distribution of 5-HT 2A receptors, but not with known concentration profiles of dopaminergic D 2 or adrenergic α 1 receptors. Finally, detectable specific binding was abolished by pretreatment with large doses of ritanserin, a selective 5-HT 2A antagonist, which resulted in uniform uptakes across cortical, striatal and cerebellar tissues. Thus, [ 18 F]RP 62203 appears to be a promising selective tool to visualize and quantify 5-HT 2A brain receptors in vivo with positron emission tomography

  11. Waterborne fluoride exposure changed the structure and the expressions of steroidogenic-related genes in gonads of adult zebrafish (Danio rerio).

    Science.gov (United States)

    Li, MeiYan; Cao, Jinling; Chen, Jianjie; Song, Jie; Zhou, Bingrui; Feng, Cuiping; Wang, Jundong

    2016-02-01

    Excessive fluoride in natural water ecosystem has been demonstrated to have adverse effects on reproductive system in humans and mammals, while the most vulnerable aquatic organisms were ignored. In this study, the effects of waterborne fluoride on growth performance, sex steroid hormone, histological structure, and the transcriptional profiles of sex steroid related genes were examined in both female and male zebrafish exposed to different concentrations of 0.79, 18.60, 36.83 mg L(-1) of fluoride for 30 and 60 d to investigate the effects of fluoride on reproductive system and the underlying toxic mechanisms caused by fluoride. The results showed that the body weight was remarkably decreased, the structure of ovary and testis were serious injured, and the T and E2 levels were significantly reduced in male zebrafish. The transcriptional profiles of steroidogenic related genes displayed phenomenal alterations, the expressions of pgr and cyp19a1a were significantly up-regulated, while the transcriptional levels of er, ar and hsd3β were decreased both in the ovary and testis, and hsd17β8 were down-regulated just in males. Taken together, these results demonstrated that fluoride could significantly inhibit the growth of zebrafish, and notably affect the reproductive system in both sex zebrafish by impairing the structure of ovary and testis, altering steroid hormone levels and steroidogenic genes expression related to the synthesis of sex hormones in zebrafish. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. A selective HDAC 1/2 inhibitor modulates chromatin and gene expression in brain and alters mouse behavior in two mood-related tests.

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    Frederick A Schroeder

    Full Text Available Psychiatric diseases, including schizophrenia, bipolar disorder and major depression, are projected to lead global disease burden within the next decade. Pharmacotherapy, the primary--albeit often ineffective--treatment method, has remained largely unchanged over the past 50 years, highlighting the need for novel target discovery and improved mechanism-based treatments. Here, we examined in wild type mice the impact of chronic, systemic treatment with Compound 60 (Cpd-60, a slow-binding, benzamide-based inhibitor of the class I histone deacetylase (HDAC family members, HDAC1 and HDAC2, in mood-related behavioral assays responsive to clinically effective drugs. Cpd-60 treatment for one week was associated with attenuated locomotor activity following acute amphetamine challenge. Further, treated mice demonstrated decreased immobility in the forced swim test. These changes are consistent with established effects of clinical mood stabilizers and antidepressants, respectively. Whole-genome expression profiling of specific brain regions (prefrontal cortex, nucleus accumbens, hippocampus from mice treated with Cpd-60 identified gene expression changes, including a small subset of transcripts that significantly overlapped those previously reported in lithium-treated mice. HDAC inhibition in brain was confirmed by increased histone acetylation both globally and, using chromatin immunoprecipitation, at the promoter regions of upregulated transcripts, a finding consistent with in vivo engagement of HDAC targets. In contrast, treatment with suberoylanilide hydroxamic acid (SAHA, a non-selective fast-binding, hydroxamic acid HDAC 1/2/3/6 inhibitor, was sufficient to increase histone acetylation in brain, but did not alter mood-related behaviors and had dissimilar transcriptional regulatory effects compared to Cpd-60. These results provide evidence that selective inhibition of HDAC1 and HDAC2 in brain may provide an epigenetic-based target for developing

  13. Evaluation of JNJ-54717793 a Novel Brain Penetrant Selective Orexin 1 Receptor Antagonist in Two Rat Models of Panic Attack Provocation

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    Pascal Bonaventure

    2017-06-01

    Full Text Available Orexin neurons originating in the perifornical and lateral hypothalamic area are highly reactive to anxiogenic stimuli and have strong projections to anxiety and panic-associated circuitry. Recent studies support a role for the orexin system and in particular the orexin 1 receptor (OX1R in coordinating an integrative stress response. However, no selective OX1R antagonist has been systematically tested in two preclinical models of using panicogenic stimuli that induce panic attack in the majority of people with panic disorder, namely an acute hypercapnia-panic provocation model and a model involving chronic inhibition of GABA synthesis in the perifornical hypothalamic area followed by intravenous sodium lactate infusion. Here we report on a novel brain penetrant, selective and high affinity OX1R antagonist JNJ-54717793 (1S,2R,4R-7-([(3-fluoro-2-pyrimidin-2-ylphenylcarbonyl]-N-[5-(trifluoromethylpyrazin-2-yl]-7-azabicyclo[2.2.1]heptan-2-amine. JNJ-54717793 is a high affinity/potent OX1R antagonist and has an excellent selectivity profile including 50 fold versus the OX2R. Ex vivo receptor binding studies demonstrated that after oral administration JNJ-54717793 crossed the blood brain barrier and occupied OX1Rs in the rat brain. While JNJ-54717793 had minimal effect on spontaneous sleep in rats and in wild-type mice, its administration in OX2R knockout mice, selectively promoted rapid eye movement sleep, demonstrating target engagement and specific OX1R blockade. JNJ-54717793 attenuated CO2 and sodium lactate induced panic-like behaviors and cardiovascular responses without altering baseline locomotor or autonomic activity. These data confirm that selective OX1R antagonism may represent a novel approach of treating anxiety disorders, with no apparent sedative effects.

  14. A novel muscarinic receptor ligand which penetrates the blood brain barrier and displays in vivo selectivity for the m2 subtype

    International Nuclear Information System (INIS)

    Gitler, M.S.; Cohen, V.I.; De La Cruz, R.; Boulay, S.F.; Jin, B.; Zeeberg, B.R.; Reba, R.C.

    1993-01-01

    Alzheimer's disease (AD) involves selective loss of muscarinic m2, but not m1, subtype neuroreceptors in the posterior parietal cortex of the human brain. Emission tomographic study of the loss of m2 receptors in AD is limited by the fact that there is currently no available m2-selective radioligand which can penetrate the blood-brain barrier. In our efforts to prepare such a radioligand, the authors have used competition studies against currently existing muscarinic receptor radioligands to infer the in vitro and in vivo properties of a novel muscarinic receptor ligand, 5-[[4-[4-(diisobutylamino)butyl]-1-phenyl]acetyl]-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-11-one (DIBD). In vitro competition studies against [ 3 H](R)-3-quinuclidinylbenzilate ([ 3 H]QNB) and [ 3 H]N-methylscopolamine ([ 3 H]NMS), using membranes derived from transfected cells expressing only m1, m2, m3, or m4 receptor subtypes, indicate that DIBD is selective for m2/m4 over m1/m3. In vivo competition studies against (R,R)-[ 125 I]IQNB indicate that DIBD crosses the blood brain barrier (BBB). The relationship of the regional percentage decrease in (R,R)-[ 125 I]IQNB versus the percentage of each of the receptor subtypes indicates that DIBD competes more effectively in those brain regions which are known to be enriched in the m2, relative to the m1, m3, and m4, receptor subtype; however, analysis of the data using a mathematical model shows that caution is required when interpreting the in vivo results. The authors conclude that a suitably radiolabeled derivative of DIBD may be of potential use in emission tomographic study of changes in m2 receptors in the central nervous system

  15. Selective deficit of second language: a case study of a brain-damaged Arabic-Hebrew bilingual patient

    Directory of Open Access Journals (Sweden)

    Ibrahim Raphiq

    2009-03-01

    Full Text Available Abstract Background An understanding of how two languages are represented in the human brain is best obtained from studies of bilingual patients who have sustained brain damage. The primary goal of the present study was to determine whether one or both languages of an Arabic-Hebrew bilingual individual are disrupted following brain damage. I present a case study of a bilingual patient, proficient in Arabic and Hebrew, who had sustained brain damage as a result of an intracranial hemorrhage related to herpes encephalitis. Methods The patient's performance on several linguistic tasks carried out in the first language (Arabic and in the second language (Hebrew was assessed, and his performance in the two languages was compared. Results The patient displayed somewhat different symptomatologies in the two languages. The results revealed dissociation between the two languages in terms of both the types and the magnitude of errors, pointing to aphasic symptoms in both languages, with Hebrew being the more impaired. Further analysis disclosed that this dissociation was apparently caused not by damage to his semantic system, but rather by damage at the lexical level. Conclusion The results suggest that the principles governing the organization of lexical representations in the brain are not similar for the two languages.

  16. Selective Limbic Blood–Brain Barrier Breakdown in a Feline Model of Limbic Encephalitis with LGI1 Antibodies

    Science.gov (United States)

    Tröscher, Anna R.; Klang, Andrea; French, Maria; Quemada-Garrido, Lucía; Kneissl, Sibylle Maria; Bien, Christian G.; Pákozdy, Ákos; Bauer, Jan

    2017-01-01

    Human leucine-rich glioma-inactivated protein 1 encephalitis (LGI1) is an autoimmune limbic encephalitis in which serum and cerebrospinal fluid contain antibodies targeting LGI1, a protein of the voltage gated potassium channel (VGKC) complex. Recently, we showed that a feline model of limbic encephalitis with LGI1 antibodies, called feline complex partial seizures with orofacial involvement (FEPSO), is highly comparable to human LGI1 encephalitis. In human LGI1 encephalitis, neuropathological investigations are difficult because very little material is available. Taking advantage of this natural animal model to study pathological mechanisms will, therefore, contribute to a better understanding of its human counterpart. Here, we present a brain-wide histopathological analysis of FEPSO. We discovered that blood–brain barrier (BBB) leakage was present not only in all regions of the hippocampus but also in other limbic structures such as the subiculum, amygdale, and piriform lobe. However, in other regions, such as the cerebellum, no leakage was observed. In addition, this brain-region-specific immunoglobulin leakage was associated with the breakdown of endothelial tight junctions. Brain areas affected by BBB dysfunction also revealed immunoglobulin and complement deposition as well as neuronal cell death. These neuropathological findings were supported by magnetic resonance imaging showing signal and volume increase in the amygdala and the piriform lobe. Importantly, we could show that BBB disturbance in LGI1 encephalitis does not depend on T cell infiltrates, which were present brain-wide. This finding points toward another, so far unknown, mechanism of opening the BBB. The limbic predilection sites of immunoglobulin antibody leakage into the brain may explain why most patients with LGI1 antibodies have a limbic phenotype even though LGI1, the target protein, is ubiquitously distributed across the central nervous system. PMID:29093718

  17. Selective Limbic Blood–Brain Barrier Breakdown in a Feline Model of Limbic Encephalitis with LGI1 Antibodies

    Directory of Open Access Journals (Sweden)

    Anna R. Tröscher

    2017-10-01

    Full Text Available Human leucine-rich glioma-inactivated protein 1 encephalitis (LGI1 is an autoimmune limbic encephalitis in which serum and cerebrospinal fluid contain antibodies targeting LGI1, a protein of the voltage gated potassium channel (VGKC complex. Recently, we showed that a feline model of limbic encephalitis with LGI1 antibodies, called feline complex partial seizures with orofacial involvement (FEPSO, is highly comparable to human LGI1 encephalitis. In human LGI1 encephalitis, neuropathological investigations are difficult because very little material is available. Taking advantage of this natural animal model to study pathological mechanisms will, therefore, contribute to a better understanding of its human counterpart. Here, we present a brain-wide histopathological analysis of FEPSO. We discovered that blood–brain barrier (BBB leakage was present not only in all regions of the hippocampus but also in other limbic structures such as the subiculum, amygdale, and piriform lobe. However, in other regions, such as the cerebellum, no leakage was observed. In addition, this brain-region-specific immunoglobulin leakage was associated with the breakdown of endothelial tight junctions. Brain areas affected by BBB dysfunction also revealed immunoglobulin and complement deposition as well as neuronal cell death. These neuropathological findings were supported by magnetic resonance imaging showing signal and volume increase in the amygdala and the piriform lobe. Importantly, we could show that BBB disturbance in LGI1 encephalitis does not depend on T cell infiltrates, which were present brain-wide. This finding points toward another, so far unknown, mechanism of opening the BBB. The limbic predilection sites of immunoglobulin antibody leakage into the brain may explain why most patients with LGI1 antibodies have a limbic phenotype even though LGI1, the target protein, is ubiquitously distributed across the central nervous system.

  18. Selective Limbic Blood-Brain Barrier Breakdown in a Feline Model of Limbic Encephalitis with LGI1 Antibodies.

    Science.gov (United States)

    Tröscher, Anna R; Klang, Andrea; French, Maria; Quemada-Garrido, Lucía; Kneissl, Sibylle Maria; Bien, Christian G; Pákozdy, Ákos; Bauer, Jan

    2017-01-01

    Human leucine-rich glioma-inactivated protein 1 encephalitis (LGI1) is an autoimmune limbic encephalitis in which serum and cerebrospinal fluid contain antibodies targeting LGI1, a protein of the voltage gated potassium channel (VGKC) complex. Recently, we showed that a feline model of limbic encephalitis with LGI1 antibodies, called feline complex partial seizures with orofacial involvement (FEPSO), is highly comparable to human LGI1 encephalitis. In human LGI1 encephalitis, neuropathological investigations are difficult because very little material is available. Taking advantage of this natural animal model to study pathological mechanisms will, therefore, contribute to a better understanding of its human counterpart. Here, we present a brain-wide histopathological analysis of FEPSO. We discovered that blood-brain barrier (BBB) leakage was present not only in all regions of the hippocampus but also in other limbic structures such as the subiculum, amygdale, and piriform lobe. However, in other regions, such as the cerebellum, no leakage was observed. In addition, this brain-region-specific immunoglobulin leakage was associated with the breakdown of endothelial tight junctions. Brain areas affected by BBB dysfunction also revealed immunoglobulin and complement deposition as well as neuronal cell death. These neuropathological findings were supported by magnetic resonance imaging showing signal and volume increase in the amygdala and the piriform lobe. Importantly, we could show that BBB disturbance in LGI1 encephalitis does not depend on T cell infiltrates, which were present brain-wide. This finding points toward another, so far unknown, mechanism of opening the BBB. The limbic predilection sites of immunoglobulin antibody leakage into the brain may explain why most patients with LGI1 antibodies have a limbic phenotype even though LGI1, the target protein, is ubiquitously distributed across the central nervous system.

  19. BDNF/TrkB Signaling as a Potential Novel Target in Pediatric Brain Tumors: Anticancer Activity of Selective TrkB Inhibition in Medulloblastoma Cells.

    Science.gov (United States)

    Thomaz, Amanda; Jaeger, Mariane; Buendia, Marienela; Bambini-Junior, Victorio; Gregianin, Lauro José; Brunetto, Algemir Lunardi; Brunetto, André T; de Farias, Caroline Brunetto; Roesler, Rafael

    2016-07-01

    Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment.

  20. An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues.

    Science.gov (United States)

    Saraco, Nora; Nesi-Franca, Suzana; Sainz, Romina; Marino, Roxana; Marques-Pereira, Rosana; La Pastina, Julia; Perez Garrido, Natalia; Sandrini, Romolo; Rivarola, Marco Aurelio; de Lacerda, Luiz; Belgorosky, Alicia

    2015-01-01

    Splicing CYP19 gene variants causing aromatase deficiency in 46,XX disorder of sexual development (DSD) patients have been reported in a few cases. A misbalance between normal and aberrant splicing variants was proposed to explain spontaneous pubertal breast development but an incomplete sex maturation progress. The aim of this study was to functionally characterize a novel CYP19A1 intronic homozygote mutation (IVS9+5G>A) in a 46,XX DSD girl presenting spontaneous breast development and primary amenorrhea, and to evaluate similar splicing variant expression in normal steroidogenic tissues. Genomic DNA analysis, splicing prediction programs, splicing assays, and in vitro protein expression and enzyme activity analyses were carried out. CYP19A1 mRNA expression in human steroidogenic tissues was also studied. A novel IVS9+5G>A homozygote mutation was found. In silico analysis predicts the disappearance of the splicing donor site in intron 9, confirmed by patient peripheral leukocyte cP450arom and in vitro studies. Protein analysis showed a shorter and inactive protein. The intron 9 transcript variant was also found in human steroidogenic tissues. The mutation IVS9+5G>A generates a splicing variant that includes intron 9 which is also present in normal human steroidogenic tissues, suggesting that a misbalance between normal and aberrant splicing variants might occur in target tissues, explaining the clinical phenotype in the affected patient. © 2015 S. Karger AG, Basel.

  1. Adenoviral vectors for highly selective gene expression in central serotonergic neurons reveal quantal characteristics of serotonin release in the rat brain

    Directory of Open Access Journals (Sweden)

    Teschemacher Anja G

    2009-03-01

    Full Text Available Abstract Background 5-hydroxytryptamine (5 HT, serotonin is one of the key neuromodulators in mammalian brain, but many fundamental properties of serotonergic neurones and 5 HT release remain unknown. The objective of this study was to generate an adenoviral vector system for selective targeting of serotonergic neurones and apply it to study quantal characteristics of 5 HT release in the rat brain. Results We have generated adenoviral vectors which incorporate a 3.6 kb fragment of the rat tryptophan hydroxylase-2 (TPH-2 gene which selectively (97% co-localisation with TPH-2 target raphe serotonergic neurones. In order to enhance the level of expression a two-step transcriptional amplification strategy was employed. This allowed direct visualization of serotonergic neurones by EGFP fluorescence. Using these vectors we have performed initial characterization of EGFP-expressing serotonergic neurones in rat organotypic brain slice cultures. Fluorescent serotonergic neurones were identified and studied using patch clamp and confocal Ca2+ imaging and had features consistent with those previously reported using post-hoc identification approaches. Fine processes of serotonergic neurones could also be visualized in un-fixed tissue and morphometric analysis suggested two putative types of axonal varicosities. We used micro-amperometry to analyse the quantal characteristics of 5 HT release and found that central 5 HT exocytosis occurs predominantly in quanta of ~28000 molecules from varicosities and ~34000 molecules from cell bodies. In addition, in somata, we observed a minority of large release events discharging on average ~800000 molecules. Conclusion For the first time quantal release of 5 HT from somato-dendritic compartments and axonal varicosities in mammalian brain has been demonstrated directly and characterised. Release from somato-dendritic and axonal compartments might have different physiological functions. Novel vectors generated in this

  2. Potassium-selective microelectrode revealed difference in threshold potassium concentration for cortical spreading depression in female and male rat brain

    Czech Academy of Sciences Publication Activity Database

    Adámek, S.; Vyskočil, František

    2011-01-01

    Roč. 1370, - (2011), s. 215-219 ISSN 0006-8993 R&D Projects: GA AV ČR(CZ) IAA500110905 Institutional research plan: CEZ:AV0Z50110509 Keywords : rat cortex * potassium in brain Subject RIV: ED - Physiology Impact factor: 2.728, year: 2011

  3. User Adapted Motor-Imaginary Brain-Computer Interface by means of EEG Channel Selection Based on Estimation of Distributed Algorithms

    Directory of Open Access Journals (Sweden)

    Aitzol Astigarraga

    2016-01-01

    Full Text Available Brain-Computer Interfaces (BCIs have become a research field with interesting applications, and it can be inferred from published papers that different persons activate different parts of the brain to perform the same action. This paper presents a personalized interface design method, for electroencephalogram- (EEG- based BCIs, based on channel selection. We describe a novel two-step method in which firstly a computationally inexpensive greedy algorithm finds an adequate search range; and, then, an Estimation of Distribution Algorithm (EDA is applied in the reduced range to obtain the optimal channel subset. The use of the EDA allows us to select the most interacting channels subset, removing the irrelevant and noisy ones, thus selecting the most discriminative subset of channels for each user improving accuracy. The method is tested on the IIIa dataset from the BCI competition III. Experimental results show that the resulting channel subset is consistent with motor-imaginary-related neurophysiological principles and, on the other hand, optimizes performance reducing the number of channels.

  4. Single-photon emission tomography imaging of serotonin transporters in the non-human primate brain with the selective radioligand [[sup 123]I]IDAM

    Energy Technology Data Exchange (ETDEWEB)

    Acton, P.D.; Kung Mei-Ping; Mu Mu; Ploessl, K.; Hou, C.; Siciliano, M.; Oya Shunichi (Department of Radiology, University of Pennsylvania, Philadelphia, PA (United States)); Kung, H.F. (Department of Radiology, University of Pennsylvania, Philadelphia, PA (United States) Department of Pharmacology, University of Pennsylvania, Philadelphia (United States))

    1999-08-01

    A new radioligand, 5-iodo-2-[[2-2-[(dimethylamino)methyl]phenyl]thio]benzyl alcohol ([[sup 123]I]IDAM), has been developed for selective single-photon emission tomography (SPET) imaging of SERT. In vitro binding studies suggest a high selectivity of IDAM for SERT (K[sub i]=0.097 nM), with considerably lower affinities for norepinephrine and dopamine transporters (NET K[sub i]= 234 nM and DAT K[sub i]>10 [mu]M, respectively). In this study the biodistribution of SERT in the baboon brain was investigated in vivo using [[sup 123]I]IDAM and SPET imaging. Dynamic sequences of SPET scans were performed on three female baboons (Papio anubis) after injection of 555 MBq of [[sup 123]I]IDAM. Displacing doses (1 mg/kg) of the selective SERT ligand (+)McN5652 were administered 90-120 min after injection of [[sup 123]I]IDAM. Similar studies were performed using a NET inhibitor, nisoxetine, and a DAT blocker, methylphenidate. After 60-120 min, the regional distribution of tracer within the brain reflected the characteristic distribution of SERT, with the highest uptake in the midbrain area (hypothalamus, raphe nucleus, substantia nigra), and the lowest uptake in the cerebellum (an area presumed free of SERT). Peak specific binding in the midbrain occurred at 120 min, with a ratio to the cerebellum of 1.80[+-]0.13. At 30 min, 85% of the radioactivity in the blood was metabolite. Following injection of a competing SERT ligand, (+)McN5652, the tracer exhibited rapid washout from areas with high concentrations of SERT (dissociation rate constant in the midbrain, averaged over three baboons, k[sub off]=0.025[+-]0.002 min[sup -1]), while the cerebellar activity distribution was undisturbed (washout rate 0.0059[+-] 0.0003 min[sup -1]). Calculation of tracer washout rate pixel-by-pixel enabled the generation of parametric images of the dissociation rate constant. Similar studies using nisoxetine and methylphenidate had no effect on the distribution of [[sup 123]I]IDAM in the brain

  5. Steroidogenic disruptive effects of the serotonin-noradrenaline reuptake inhibitors duloxetine, venlafaxine and tramadol in the H295R cell assay and in a recombinant CYP17 assay

    DEFF Research Database (Denmark)

    Islin, Julie; Munkboel, Cecilie Hurup; Styrishave, Bjarne

    2018-01-01

    The aim of this study was to determine the steroidogenic endocrine disrupting effect of the three most widely used serotonin-noradrenaline reuptake inhibitors duloxetine, venlafaxine and tramadol, using two in vitro models, the H295R assay and a recombinant CYP17 enzyme assay. Steroid hormones were...... quantified using LC-MS/MS. Duloxetine showed endocrine disrupting effects at 5-20μM with CYP17 being the main target. Venlafaxine also affected the steroidogenesis, mainly by affecting the CYP17 lyase reaction, although at much higher concentrations i.e. 100μM. Tramadol only exerted minor effects...... on the steroidogenesis with the lowest observed effect at 314μM. Based on the H295R results, the inhibition of CYP17 by duloxetine and venlafaxine was investigated in a recombinant CYP17 assay with the use of the 4 major CYP17 substrates pregnenolone, progesterone, 17α-hydroxypregnenolone and 17α...

  6. Acute pharmacologically induced shifts in serotonin availability abolish emotion-selective responses to negative face emotions in distinct brain networks

    DEFF Research Database (Denmark)

    Grady, Cheryl Lynn; Siebner, Hartwig R; Hornboll, Bettina

    2013-01-01

    Pharmacological manipulation of serotonin availability can alter the processing of facial expressions of emotion. Using a within-subject design, we measured the effect of serotonin on the brain's response to aversive face emotions with functional MRI while 20 participants judged the gender...... of neutral, fearful and angry faces. In three separate and counterbalanced sessions, participants received citalopram (CIT) to raise serotonin levels, underwent acute tryptophan depletion (ATD) to lower serotonin, or were studied without pharmacological challenge (Control). An analysis designed to identify...

  7. Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Biegon, A.; Alvarado, M.; Budinger, T.F.; Grossman, R.; Hensley, K.; West, M.S.; Kotake, Y.; Ono, M.; Floyd, R.A.

    2001-12-10

    Following induction of acute neuroinflammation by intracisternal injection of endotoxin (lipopolysaccharide) in rats, quantitative autoradiography was used to assess the regional level of microglial activation and glutamate (NMDA) receptor binding. The possible protective action of the antioxidant phenyl-tert-butyl nitrone in this model was tested by administering the drug in the drinking water for 6 days starting 24 hours after endotoxin injection. Animals were killed 7 days post-injection and consecutive cryostat brain sections labeled with [3H]PK11195 as a marker of activated microglia and [125I]iodoMK801 as a marker of the open-channel, activated state of NMDA receptors. Lipopolysaccharide increased [3H]PK11195 binding in the brain, with the largest increases (2-3 fold) in temporal and entorhinal cortex, hippocampus, and substantia innominata. A significant (>50 percent) decrease in [125I]iodoMK801 binding was found in the same brain regions. Phenyl-tert-butyl nitrone treatment resulted in a partial inhibition ({approx}25 percent decrease) of the lipopolysaccharide-induced increase in [3H]PK11195 binding but completely reversed the lipopolysaccharide-induced decrease in [125I]iodoMK80 binding in the entorhinal cortex, hippocampus, and substantia innominata. Loss of NMDA receptor function in cortical and hippocampal regions may contribute to the cognitive deficits observed in diseases with a neuroinflammatory component, such as meningitis or Alzheimer's disease.

  8. Differential insulin and steroidogenic signaling in insulin resistant and non-insulin resistant human luteinized granulosa cells-A study in PCOS patients.

    Science.gov (United States)

    Belani, Muskaan; Deo, Abhilash; Shah, Preeti; Banker, Manish; Singal, Pawan; Gupta, Sarita

    2018-04-01

    Insulin resistance (IR) is one of the significant aberrations in polycystic ovarian syndrome (PCOS), however is only observed in 70%-80% of obese PCOS and 20%-25% of lean PCOS. Hyperinsulinemia accompanies PCOS-IR along with hyperandrogenemia against normal insulin and androgen levels in PCOS-non insulin resistance (NIR). This could possibly be due to defects in the downstream signaling pathways. The study thus aims to unravel insulin and steroidogenic signaling pathways in luteinized granulosa cells isolated from PCOS-IR and NIR vs matched controls. Luteinized granulosa cells from 30 controls and 39 PCOS were classified for IR based on a novel method of down regulation of protein expression of insulin receptor-β (INSR- β) as shown in our previous paper. We evaluated expression of molecules involved in insulin, steroidogenic signaling and lipid metabolism in luteinized granulosa cells followed by analysis of estradiol, progesterone and testosterone in follicular fluid. Protein expression of INSR- β, pIRS (ser 307), PI(3)K, PKC-ζ, pAkt, ERK1/2, pP38MAPK and gene expression of IGF showed differential expression in the two groups. Increased protein expression of PPAR-γ was accompanied by up regulation in SREBP1c, FAS, CPT-1 and ACC-1 genes in PCOS-IR group. Expression of StAR, CYP19A1, 17 β- HSD and 3 β- HSD demonstrated significant decrease along with increase in CYP11A1, FSH-R and LH-R in both the groups. Follicular fluid testosterone increased and progesterone decreased in PCOS-IR group. This study shows how candidate molecules that were differentially expressed, aid in designing targeted therapy against the two phenotypes of PCOS. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Growth differentiation factor 9 reverses activin A suppression of steroidogenic acute regulatory protein expression and progesterone production in human granulosa-lutein cells.

    Science.gov (United States)

    Shi, Feng-Tao; Cheung, Anthony P; Klausen, Christian; Huang, He-Feng; Leung, Peter C K

    2010-10-01

    We have reported that growth differentiation factor 9 (GDF9) can enhance activin A (β(A)β(A))-induced inhibin B (αβ(B)) secretion in human granulosa-lutein (hGL) cells, but its effects on steroidogenic acute regulatory protein (StAR), ovarian steroidogenic enzymes, and progesterone production are unknown. We undertook this study to further evaluate GDF9 in this regard. hGL cells from women undergoing in vitro fertilization treatment were cultured with and without small interfering RNA (siRNA) transfection targeted at inhibin α-subunit or GDF9 before treatment with GDF9, activin A, FSH, or combinations. We compared StAR, P450 side-chain cleavage enzyme, and 3β-hydroxysteroid dehydrogenase expression in hGL cells and progesterone levels in culture media after these treatments. mRNA, protein, and hormone levels were assessed with real-time RT-PCR, immunoblotting, and ELISA, respectively. Data were analyzed by ANOVA followed by Tukey's test. Activin A alone reduced basal and FSH-induced progesterone production by decreasing the expression of StAR protein, which regulates the rate-limiting step in steroidogenesis but not P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase. GDF9 attenuated these activin A effects on StAR and progesterone. After transfection of α-subunit siRNA, activin A level increased (P progesterone production were attenuated (P progesterone secretion than those observed with activin A treatment alone. GDF9 attenuates the suppressive effects of activin A on StAR expression and progesterone production by increasing the expression of inhibin B, which acts as an activin A competitor.

  10. 1,3-Dichloro-2-propanol inhibits progesterone production through the expression of steroidogenic enzymes and cAMP concentration in Leydig cells.

    Science.gov (United States)

    Sun, Jianxia; Bai, Shun; Bai, Weibin; Zou, Feiyan; Zhang, Lei; Li, Guoqiang; Hu, Yunfeng; Li, Mingwei; Yan, Rian; Su, Zhijian; Huang, Yadong

    2014-07-01

    1,3-Dichloro-2-propanol (1,3-DCP) is a well-known food processing contaminant that has been shown to impede male reproductive function. However, its mechanism of action remains elusive. In this study, the effects of 1,3-DCP on progesterone production were investigated using the R2C Leydig cell model. 1,3-DCP significantly reduced cell viability from 7.48% to 97.4% at doses comprised between 0.5 and 6mM. Single cell gel/comet assays and atomic force microscopy assays showed that 1,3-DCP induced early phase cell apoptosis. In addition, 1,3-DCP significantly reduced progesterone production detected by radioimmunoassay (RIA). The results from quantitative polymerase chain reaction and western blotting demonstrated that the mRNA expression levels of steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase were significantly down-regulated in R2C cells. Particularly, the change rhythm of Star expression was highly consistent with progesterone production. Furthermore, the cyclic adenosine monophosphate (cAMP) and the mitochondrial membrane potential mediated by ROS, which are involved in regulating progesterone synthesis were also decreased in response to the 1,3-DCP treatment. Overall, the data presented here suggested that 1,3-DCP interferes with the male steroidogenic capacity mainly by down-regulating the level of cAMP and the key enzymes involved in the androgen synthesis pathway. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Nitrophenols isolated from diesel exhaust particles regulate steroidogenic gene expression and steroid synthesis in the human H295R adrenocortical cell line

    International Nuclear Information System (INIS)

    Furuta, Chie; Noda, Shiho; Li Chunmei; Suzuki, Akira K; Taneda, Shinji; Watanabe, Gen; Taya, Kazuyoshi

    2008-01-01

    Studies of nitrophenols isolated from diesel exhaust particles (DEPs), 3-methyl-4-nitrophenol (PNMC) and 4-nitro-3-phenylphenol (PNMPP) have revealed that these chemicals possess estrogenic and anti-androgenic activity in vitro and in vivo and that PNMC accumulate in adrenal glands in vivo. However, the impacts of exposure to these compounds on adrenal endocrine disruption and steroidogenesis have not been investigated. To elucidate the non-receptor mediated effects of PNMC and PNMPP, we investigated the production of the steroid hormones progesterone, cortisol, testosterone, and estradiol-17β and modulation of nine major enzyme genes involved in the synthesis of steroid hormones (CYP11A, CYP11B1, CYP17, CYP19, 17βHSD1, 17βHSD4, CYP21, 3βHSD2, StAR) in human adrenal H295R cells supplied with cAMP. Exposure to 10 -7 to 10 -5 M PNMC and 1 mM 8-Br-cAMP for 48 h decreased testosterone, cortisol, and estradiol-17β levels and increased progesterone secretion. At 10 -5 M, PNMC with 1 mM 8-Br-cAMP significantly stimulated expression of the 17βHSD4 and significantly suppressed expression of 3βHSD2. In comparison, 10 -7 to 2 x 10 -5 M PNMPP with 1 mM 8-Br-cAMP for 48 h decreased concentrations of estradiol-17β, increased progesterone levels, but did not affect testosterone and cortisol secretion due to the significant suppression of CYP17 and the non-significant but obvious suppression of CYP19. Our results clarified steroidogenic enzymes as candidates responsible for the inhibition or stimulation for the production of steroid hormones in the steroidogenic pathway, thus providing the first experimental evidence for multiple mechanisms of disruption of endocrine pathways by these nitrophenols

  12. Effects of long-term heat stress and dietary restriction on the expression of genes of steroidogenic pathway and small heat-shock proteins in rat testicular tissue.

    Science.gov (United States)

    Bozkaya, F; Atli, M O; Guzeloglu, A; Kayis, S A; Yildirim, M E; Kurar, E; Yilmaz, R; Aydilek, N

    2017-08-01

    The aim was to investigate the effects of long-term heat stress and dietary restriction on the expression of certain genes involving in steroidogenic pathway and small heat-shock proteins (sHSPs) in rat testis. Sprague Dawley rats (n = 24) were equally divided into four groups. Group I and II were kept at an ambient temperature of 22°C, while Groups III and IV were reared at 38°C for 9 weeks. Feed was freely available for Group I and Group III, while Group II and Group IV were fed 60% of the diet consumed by their ad libitum counterparts. At the end of 9 weeks, testicles were collected under euthanasia. Total RNA was isolated from testis tissue samples. Expression profiles of the genes encoding androgen-binding protein, follicle-stimulating hormone receptor, androgen receptor, luteinising hormone receptor, steroidogenic acute regulatory protein (StAR), cyclooxygenase-2 and sHSP genes were assessed at mRNA levels using qPCR. Long-term heat stress decreased the expression of StAR and HspB10 genes while dietary restriction upregulated StAR gene expression. The results suggested that long-term heat stress negatively affected the expression of StAR and HspB10 genes and the dietary restriction was able to reverse negative effect of heat stress on the expression of StAR gene in rat testis. © 2016 Blackwell Verlag GmbH.

  13. Treatment with selective serotonin reuptake inhibitors and mirtapazine results in differential brain activation by visual erotic stimuli in patients with major depressive disorder.

    Science.gov (United States)

    Kim, Won; Jin, Bo-Ra; Yang, Wan-Seok; Lee, Kyuong-Uk; Juh, Ra-Hyung; Ahn, Kook-Jin; Chung, Yong-An; Chae, Jeong-Ho

    2009-06-01

    The objective of this study was to identify patterns of brain activation elicited by erotic visual stimuli in patients treated with either Selective Serotonin Reuptake Inhibitors (SSRIs) or mirtazipine. Nine middle-aged men with major depressive disorder treated with an SSRI and ten middle-aged men with major depressive disorder treated with mirtazapine completed the trial. Ten subjects with no psychiatric illness were included as a control group. We conducted functional brain magnetic resonance imaging (fMRI) while a film alternatively played erotic and non-erotic contents for 14 minutes and 9 seconds. The control group showed activation in the occipitotemporal area, anterior cingulate gyrus, insula, orbitofrontal cortex, and caudate nucleus. For subjects treated with SSRIs, the intensity of activity in these regions was much lower compared to the control group. Intensity of activation in the group treated with mirtazapine was less than the control group but grea-ter than those treated with SSRIs. Using subtraction analysis, the SSRI group showed significantly lower activation than the mirtazapine group in the anterior cingulate gyrus and the caudate nucleus. Our study suggests that the different rates of sexual side effects between the patients in the SSRI-treated group and the mirtazapine-treated group may be due to different effects on brain activation.

  14. A Genetic-Based Feature Selection Approach in the Identification of Left/Right Hand Motor Imagery for a Brain-Computer Interface.

    Science.gov (United States)

    Yaacoub, Charles; Mhanna, Georges; Rihana, Sandy

    2017-01-23

    Electroencephalography is a non-invasive measure of the brain electrical activity generated by millions of neurons. Feature extraction in electroencephalography analysis is a core issue that may lead to accurate brain mental state classification. This paper presents a new feature selection method that improves left/right hand movement identification of a motor imagery brain-computer interface, based on genetic algorithms and artificial neural networks used as classifiers. Raw electroencephalography signals are first preprocessed using appropriate filtering. Feature extraction is carried out afterwards, based on spectral and temporal signal components, and thus a feature vector is constructed. As various features might be inaccurate and mislead the classifier, thus degrading the overall system performance, the proposed approach identifies a subset of features from a large feature space, such that the classifier error rate is reduced. Experimental results show that the proposed method is able to reduce the number of features to as low as 0.5% (i.e., the number of ignored features can reach 99.5%) while improving the accuracy, sensitivity, specificity, and precision of the classifier.

  15. A Genetic-Based Feature Selection Approach in the Identification of Left/Right Hand Motor Imagery for a Brain-Computer Interface

    Directory of Open Access Journals (Sweden)

    Charles Yaacoub

    2017-01-01

    Full Text Available Electroencephalography is a non-invasive measure of the brain electrical activity generated by millions of neurons. Feature extraction in electroencephalography analysis is a core issue that may lead to accurate brain mental state classification. This paper presents a new feature selection method that improves left/right hand movement identification of a motor imagery brain-computer interface, based on genetic algorithms and artificial neural networks used as classifiers. Raw electroencephalography signals are first preprocessed using appropriate filtering. Feature extraction is carried out afterwards, based on spectral and temporal signal components, and thus a feature vector is constructed. As various features might be inaccurate and mislead the classifier, thus degrading the overall system performance, the proposed approach identifies a subset of features from a large feature space, such that the classifier error rate is reduced. Experimental results show that the proposed method is able to reduce the number of features to as low as 0.5% (i.e., the number of ignored features can reach 99.5% while improving the accuracy, sensitivity, specificity, and precision of the classifier.

  16. Prospective comparative study of brain protection in total aortic arch replacement: deep hypothermic circulatory arrest with retrograde cerebral perfusion or selective antegrade cerebral perfusion.

    Science.gov (United States)

    Okita, Y; Minatoya, K; Tagusari, O; Ando, M; Nagatsuka, K; Kitamura, S

    2001-07-01

    The purpose of this study was to compare the results of total aortic arch replacement using two different methods of brain protection, particularly with respect to neurologic outcome. From June 1997, 60 consecutive patients who underwent total arch replacement through a midsternotomy were alternately allocated to one of two methods of brain protection: deep hypothermic circulatory arrest with retrograde cerebral perfusion (RCP: 30 patients) or with selective antegrade cerebral perfusion (SCP: 30 patients). Preoperative and postoperative (3 weeks) brain CT scan, neurological examination, and cognitive function tests were performed. Serum 100b protein was assayed before and after the cardiopulmonary bypass, as well as 24 hours and 48 hours after the operation. Hospital mortality occurred in 2 patients in the RCP group (6.6%) and 2 in the SCP group (6.6%). New strokes occurred in 1 (3.3%) of the RCP group and in 2 (6.6%) of the SCP group (p = 0.6). The incidence of transient brain dysfunction was significantly higher in the RCP group than in the SCP group (10, 33.3% vs 4, 13.3%, p = 0.05). Except in patients with strokes, S-100b values showed no significant differences in the two groups (RCP: SCP, prebypass 0.01+/-0.04: 0.05+/-0.16, postbypass 2.17+/-0.94: 1.97+/-1.00, 24 hours 0.61+/-0.36: 0.60+/-0.37, 48 hours 0.36+/-0.45: 0.46+/-0.40 microg/L, p = 0.7). There were no intergroup differences in the scores of memory decline (RCP 0.74+/-0.99; SCP 0.55+/-1.19, p = 0.6), orientation (RCP 1.11+/-1.29; SCP 0.50+/-0.76, p = 0.08), or intellectual function (RCP 1.21+/-1.27; SCP 1.05+/-1.15, p = 0.7). Both methods of brain protection for patients undergoing total arch replacement resulted in acceptable levels of mortality and morbidity. However, the prevalence of transient brain dysfunction was significantly higher in patients with the RCP.

  17. Integral dose delivered to normal brain with conventional intensity-modulated radiotherapy (IMRT) and helical tomotherapy IMRT during partial brain radiotherapy for high-grade gliomas with and without selective sparing of the hippocampus, limbic circuit and neural stem cell compartment

    International Nuclear Information System (INIS)

    Marsh, James C.; Ziel, Ellis G; Diaz, Aidnag Z; Turian, Julius V; Wendt, Julie A.; Gobole, Rohit

    2013-01-01

    We compared integral dose with uninvolved brain (ID brain ) during partial brain radiotherapy (PBRT) for high-grade glioma patients using helical tomotherapy (HT) and seven field traditional inverse-planned intensity-modulated radiotherapy (IMRT) with and without selective sparing (SPA) of contralateral hippocampus, neural stem cell compartment (NSC) and limbic circuit. We prepared four PBRT treatment plans for four patients with high-grade gliomas (60Gy in 30 fractions delivered to planning treatment volume (PTV60Gy)). For all plans, a structure denoted 'uninvolved brain' was created, which included all brain tissue not part of PTV or standard (STD) organs at risk (OAR). No dosimetric constraints were included for uninvolved brain. Selective SPA plans were prepared with IMRT and HT; contralateral hippocampus, NSC and limbic circuit were contoured; and dosimetric constraints were entered for these structures without compromising dose to PTV or STD OAR. We compared V100 and D95 for PTV46Gy and PTV60Gy, and ID brain for all plans. There were no significant differences in V100 and D95 for PTV46Gy and PTV60Gy. ID brain was lower in traditional IMRT versus HT plans for STD and SPA plans (mean ID brain 23.64Gy vs. 28Gy and 18.7Gy vs. 24.5Gy, respectively) and in SPA versus STD plans both with IMRT and HT (18.7Gy vs. 23.64Gy and 24.5Gy vs. 28Gy, respectively). n the setting of PBRT for high-grade gliomas, IMRT reduces ID brain compared with HT with or without selective SPA of contralateral hippocampus, limbic circuit and NSC, and the use of selective SPA reduces ID brain compared with STD PBRT delivered with either traditional IMRT or HT.

  18. Selected Arterial Infusion Chemotherapy Combined with Target Drugs 
for Non-small Cell Lung Cancer with Multiple Brain Metastase

    Directory of Open Access Journals (Sweden)

    Jinduo LI

    2012-05-01

    Full Text Available Background and objective The aim of this study is to evaluate the efficacy of selected arterial infusion chemotherapy in treating non-small cell lung cancer (NSCLC with multiple brain metastases and corresponding factors to influencing prognosis. Methods From September 2008 to October 2011, a total of 31 patients of NSCLC with multiple brain metastases (≥3 received selected incranial, bronchial and corresponding target arterial infusion chemotherapy combined with EGFR-TKIs. Interventional treatment was performed every four weeks, two-six cycles with synchronized or sequential targeted drugs (erlotinib, gefitinib or icotinib. Follow-up CT and MRI were regularly finished at interval of four weeks after two cycles of interventional treatment were finished or during taking targeted drugs in order to evaluate efficacy of the therapy. The procedure was stopped for the tumor disease was worse or the patient could not tolerate the toxity of drugs any longer. Results 31 patients was performed two to six cycles of interventional therapy, 3cycles at average. Response assessment showed that 5 (16.1% patients got a complete response (CR, 7 (22.6% had a partial response (PR, 11 (35.5% had a stable disease (SD and 8 (25.8% had a progressive disease (PD. The objective response rate (ORR was 38.7%, and the disease control rate was 74.2%. The median progression free survival (PFS and overall survival (OS were 13.1 months and 15.1 months. The 6-month survival rate, one-year survival rate and two-year survival rate were 79%, 61.1%, and 31.1%, respectively. The patients’ OS and PFS were influenced by smoking state, tumor pathology, extracranial metastases, period of targeted drug taking and performance status, not by sex, age, before therapy and the total of brain metastases. Conclusion Selected arterial infusion chemotherapy with targeted drugs is one of the most effective and safe treatment to NSCLC with multiple brain metastases. Smoking status, tumor

  19. [On the role of selective silencer Freud-1 in the regulation of the brain 5-HT(1A) receptor gene expression].

    Science.gov (United States)

    Naumenko, V S; Osipova, D V; Tsybko, A S

    2010-01-01

    Selective 5-HT(1A) receptor silencer (Freud-1) is known to be one of the main factors for transcriptional regulation of brain serotonin 5-HT(1A) receptor. However, there is a lack of data on implication of Freud-1 in the mechanisms underlying genetically determined and experimentally altered 5-HT(1A) receptor system state in vivo. In the present study we have found a difference in the 5-HT(1A) gene expression in the midbrain of AKR and CBA inbred mouse strains. At the same time no distinction in Freud-1 expression was observed. We have revealed 90.3% of homology between mouse and rat 5-HT(1A) receptor DRE-element, whereas there was no difference in DRE-element sequence between AKR and CBA mice. This indicates the absence of differences in Freud-1 binding site in these mouse strains. In the model of 5-HT(1A) receptor desensitization produced by chronic 5-HT(1A) receptor agonist administration, a significant reduction of 5-HT(1A) receptor gene expression together with considerable increase of Freud-1 expression were found. These data allow us to conclude that the selective silencer of 5-HT(1A) receptor, Freud-1, is involved in the compensatory mechanisms that modulate the functional state of brain serotonin system, although it is not the only factor for 5-HT(1A) receptor transcriptional regulation.

  20. Target-Triggered Switching on and off the Luminescence of Lanthanide Coordination Polymer Nanoparticles for Selective and Sensitive Sensing of Copper Ions in Rat Brain.

    Science.gov (United States)

    Huang, Pengcheng; Wu, Fangying; Mao, Lanqun

    2015-07-07

    Copper ions (Cu(2+)) in the central nervous system play a crucial role in the physiological and pathological events, so simple, selective, and sensitive detection of cerebral Cu(2+) is of great importance. In this work, we report a facile yet effective fluorescent method for sensing of Cu(2+) in rat brain using one kind of lanthanide coordination polymer nanoparticle, adenosine monophosphate (AMP) and terbium ion (Tb(3+)), i.e., AMP-Tb, as the sensing platform. Initially, a cofactor ligand, 5-sulfosalicylic acid (SSA), as the sensitizer, was introduced into the nonluminescent AMP-Tb suspension, resulting in switching on the luminescence of AMP-Tb by the removal of coordinating water molecules and concomitant energy transfer from SSA to Tb(3+). The subsequent addition of Cu(2+) into the resulting SSA/AMP-Tb can strongly quench the fluorescence because the specific coordination interaction between SSA and Cu(2+) rendered energy transfer from SSA to Tb(3+) inefficient. The decrease ratio of the fluorescence intensities of SSA/AMP-Tb at 550 nm show a linear relationship for Cu(2+) within the concentration range from 1.5 to 24 μM with a detection limit of 300 nM. The method demonstrated here is highly selective and is free from the interference of metal ions, amino acids, and the biological species commonly existing in the brain such as dopamine, lactate, and glucose. Eventually, by combining the microdialysis technique, the present method has been successfully applied in the detection of cerebral Cu(2+) in rat brain with the basal dialysate level of 1.91 ± 0.40 μM (n = 3). This method is very promising to be used for investigating the physiological and pathological events that cerebral Cu(2+) participates in.

  1. Selective brain responses to acute and chronic low-dose X-ray irradiation in males and females

    International Nuclear Information System (INIS)

    Silasi, Greg; Diaz-Heijtz, Rochellys; Besplug, Jill; Rodriguez-Juarez, Rocio; Titov, Viktor; Kolb, Bryan; Kovalchuk, Olga

    2004-01-01

    Radiation exposure is known to have profound effects on the brain, leading to precursor cell dysfunction and debilitating cognitive declines [Nat. Med. 8 (2002) 955]. Although a plethora of data exist on the effects of high radiation doses, the effects of low-dose irradiation, such as ones received during repetitive diagnostic and therapeutic exposures, are still under-investigated [Am. J. Otolaryngol. 23 (2002) 215; Proc. Natl. Acad. Sci. USA 97 (2000) 889; Curr. Opin. Neurol. 16 (2003) 129]. Furthermore, most studies of the biological effects of ionizing radiation have been performed using a single acute dose, while clinically and environmentally relevant exposures occur predominantly under chronic/repetitive conditions. Here, we have used a mouse model to compare the effects of chronic/repetitive and acute low-dose radiation (LDR) exposure (0.5 Gy) to ionizing radiation on the brain in vivo. We examined the LDR effects on p42/44 MAPK (ERK1/ERK2), CaMKII, and AKT signaling-the interconnected pathways that have been previously shown to be crucial for neuronal survival upon irradiation. We report perturbations in ERK1/2, AKT, and CREB upon acute and chronic/repetitive low-dose exposure in the hippocampus and frontal cortex of mice. These studies were paralleled by the analysis of radiation effects on neurogenesis and cellular proliferation. Repetitive exposure had a much more pronounced effect on cellular signaling and neurogenesis than acute exposure. These results suggest that studies of single acute exposures might be limited in terms of their predictive value. We also present the first evidence of sex differences in radiation-induced signaling in the hippocampus and frontal cortex. We show the role of estrogens in brain radiation responses and discuss the implications of the observed changes

  2. Selective Changes of Resting-State Brain Oscillations in aMCI: An fMRI Study Using ALFF

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    Zhilian Zhao

    2014-01-01

    Full Text Available Mild cognitive impairment (MCI refers to a transitional state between normal aging and dementia and is a syndrome with cognitive decline greater than expected for an individual’s age and educational level. As a subtype of MCI, amnestic mild cognitive impairment (aMCI most often leads to Alzheimer’s disease. This study aims to elucidate the altered brain activation in patients with aMCI using resting-state functional magnetic resonance. We observed Frequency-dependent changes in the amplitude of low-frequency fluctuations in aMCI patients (n=20, and normal subjects (n=18. At the same time, we took gray matter volume as a covariate. We found that aMCI patients had decreased amplitude of low-frequency fluctuation signal in left superior temporal gyrus, right middle temporal gyrus, right inferior parietal lobe, and right postcentral gyrus compared to the control group. Specially, aMCI patients showed increased signal in left superior and middle frontal gyrus. Our results suggested that increased activation in frontal lobe of aMCI patients may indicate effective recruitment of compensatory brain resources. This finding and interpretation may lead to the better understanding of cognitive changes of aMCI.

  3. Differences between head CT and MRI for selecting patients for intravenous rt-PA during hyperacute brain infarction. Comparative study of intracranial bleeding complications and prognosis

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    Deguchi, Ichiro; Takeda, Hidetaka; Furuya, Daisuke

    2010-01-01

    The objective of this study was to investigate the differences in usefulness between head CT and MRI for selecting patients for intravenous injection of recombinant tissue plasminogen activator (rt-PA) during hyperacute brain infarction. Of a total of 1280 brain infarction patients who were admitted from October 2005 to March 2009, 45 patients (33 men and 12 women with an average age of 69.2±11.6 years) received intravenous rt-PA. Of these, 16 patients in whom only head CT was performed (593 inpatients from October 2005 to March 2007, CT standard group, 11 men and 5 women, average age 67.4±15.4 years) and 29 patients in whom head CT and MRI were performed (687 inpatients from April 2007 to March 2009, MRI standard group, 21 men and 7 women, average age 70.1±9.0 years) were studied. The median National Institutes of Health Stroke Scale (NIHSS) scores immediately before intravenous rt-PA for the CT and MRI standard groups were 19 and 11, respectively; disease severity was lower for the MRI standard group. Three months later, the modified Rankin Scale (mRS) score for the MRI standard group (0-1: 31%, 2-3: 38%, 4-5: 24%, and 6: 12%) was better than for the CT standard group (0-1: 25%, 2-3: 25%, 4-5: 38%, and 6: 12%). The frequency of symptomatic intracranial hemorrhage was lower for the MRI standard group (6.9%) than for the CT standard group (18.8%). However, there was no statistical difference in the prognosis and incidence of intracranial hemorrhage between the 2 groups, due to the small number of cases. When selecting patients for intravenous rt-PA, brain infarction improved more, prognosis was better three months later, and the frequency of symptomatic intracranial hemorrhage was lower among patients selected based on MRI standards than among those selected based on CT standards. (author)

  4. Atomoxetine, a selective norepinephrine reuptake inhibitor, improves short-term histological outcomes after hypoxic-ischemic brain injury in the neonatal male rat.

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    Toshimitsu, Masatake; Kamei, Yoshimasa; Ichinose, Mari; Seyama, Takahiro; Imada, Shinya; Iriyama, Takayuki; Fujii, Tomoyuki

    2018-03-30

    Despite the recent progress of perinatal medicine, perinatal hypoxic-ischemic (HI) insult remains an important cause of brain injury in neonates, and is pathologically characterized by neuronal loss and the presence of microglia. Neurotransmitters, such as norepinephrine (NE) and glutamate, are involved in the pathogenesis of hypoxic-ischemic encephalopathy via the interaction between neurons and microglia. Although it is well known that the monoamine neurotransmitter NE acts as an anti-inflammatory agent in the brain under pathological conditions, its effects on perinatal HI insult remains elusive. Atomoxetine, a selective NE reuptake inhibitor, has been used clinically for the treatment of attention-deficit hyperactivity disorder in children. Here, we investigated whether the enhancement of endogenous NE by administration of atomoxetine could protect neonates against HI insult by using the neonatal male rat model. We also examined the involvement of microglia in this process. Unilateral HI brain injury was induced by the combination of left carotid artery dissection followed by ligation and hypoxia (8% O 2 , 2 h) in postnatal day 7 (P7) male rat pups. The pups were randomized into three groups: the atomoxetine treatment immediately after HI insult, the atomoxetine treatment at 3 h after HI insult, or the vehicle treatment group. The pups were euthanized on P8 and P14, and the brain regions including the cortex, striatum, hippocampus, and thalamus were evaluated by immunohistochemistry. HI insult resulted in severe brain damage in the ipsilateral hemisphere at P14. Atomoxetine treatment immediately after HI insult significantly increased NE levels in the ipsilateral hemisphere at 1 h after HI insult and reduced the neuronal damage via the increased phosphorylation of cAMP response element-binding protein (pCREB) in all brain regions examined. In addition, the number of microglia was maintained under atomoxetine treatment compared with that of the vehicle

  5. Domestication and tameness: brain gene expression in red junglefowl selected for less fear of humans suggests effects on reproduction and immunology.

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    Bélteky, Johan; Agnvall, Beatrix; Johnsson, Martin; Wright, Dominic; Jensen, Per

    2016-08-01

    The domestication of animals has generated a set of phenotypic modifications, affecting behaviour, appearance, physiology and reproduction, which are consistent across a range of species. We hypothesized that some of these phenotypes could have evolved because of genetic correlation to tameness, an essential trait for successful domestication. Starting from an outbred population of red junglefowl, ancestor of all domestic chickens, we selected birds for either high or low fear of humans for five generations. Birds from the fifth selected generation (S 5 ) showed a divergent pattern of growth and reproduction, where low fear chickens grew larger and produced larger offspring. To examine underlying genetic mechanisms, we used microarrays to study gene expression in thalamus/hypothalamus, a brain region involved in fear and stress, in both the parental generation and the S 5 . While parents of the selection lines did not show any differentially expressed genes, there were a total of 33 genes with adjusted p -values below 0.1 in S 5 . These were mainly related to sperm-function, immunological functions, with only a few known to be relevant to behaviour. Hence, five generations of divergent selection for fear of humans produced changes in hypothalamic gene expression profiles related to pathways associated with male reproduction and to immunology. This may be linked to the effects seen on growth and size of offspring. These results support the hypothesis that domesticated phenotypes may evolve because of correlated effects related to reduced fear of humans.

  6. Dominance behaviour in a non-aggressive flatfish, Senegalese sole (Solea senegalensis and brain mRNA abundance of selected transcripts.

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    Elvira Fatsini

    Full Text Available Dominance is defined as the preferential access to limited resources. The present study aimed to characterise dominance in a non-aggressive flatfish species, the Senegalese sole (Solea senegalensis by 1 identifying dominance categories and associated behaviours and 2 linking dominance categories (dominant and subordinate with the abundance of selected mRNA transcripts in the brain. Early juveniles (n = 74, 37 pairs were subjected to a dyadic dominance test, related to feeding, and once behavioural phenotypes had been described the abundance of ten selected mRNAs related to dominance and aggressiveness was measured in the brain. Late juveniles were subjected to two dyadic dominance tests (n = 34, 17 pairs, related to feeding and territoriality and one group test (n = 24, 4 groups of 6 fish. Sole feeding first were categorized as dominant and sole feeding second or not feeding as subordinate. Three social behaviours (i. "Resting the head" on another fish, ii. "Approaching" another fish, iii. "Swimming above another" fish were associated with dominance of feeding. Two other variables (i. Total time occupying the preferred area during the last 2 hours of the 24 h test, ii. Organisms occupying the preferred area when the test ended were representative of dominance in the place preference test. In all tests, dominant fish compared to subordinate fish displayed a significantly higher number of the behaviours "Rest the head" and "Approaches". Moreover, dominant sole dominated the sand at the end of the test, and in the group test dominated the area close to the feed delivery point before feed was delivered. The mRNA abundance of the selected mRNAs related to neurogenesis (nrd2 and neuroplasticity (c-fos in dominant sole compared to subordinate were significantly different. This is the first study to characterise dominance categories with associated behaviours and mRNA abundance in Senegalese sole and provides tools to study dominance related problems in

  7. High spatial resolution and high contrast visualization of brain arteries and veins. Impact of blood pool contrast agent and water-selective excitation imaging at 3T

    International Nuclear Information System (INIS)

    Spuentrup, E.; Jacobs, J.E.; Kleimann, J.F.

    2010-01-01

    Purpose: To investigate a blood pool contrast agent and water-selective excitation imaging at 3 T for high spatial and high contrast imaging of brain vessels including the veins. Methods and Results: 48 clinical patients (47 ± 18 years old) were included. Based on clinical findings, twenty-four patients received a single dose of standard extracellular Gadoterate-meglumine (Dotarem registered ) and 24 received the blood pool contrast agent Gadofosveset (Vasovist registered ). After finishing routine MR protocols, all patients were investigated with two high spatial resolution (0.15 mm 3 voxel size) gradient echo sequences in random order in the equilibrium phase (steady-state) as approved by the review board: A standard RF-spoiled gradient-echo sequence (HR-SS, TR/TE 5.1 / 2.3 msec, FA 30 ) and a fat-suppressed gradient-echo sequence with water-selective excitation (HR-FS, 1331 binominal-pulse, TR/TE 8.8 / 3.8 msec, FA 30 ). The images were subjectively assessed (image quality with vessel contrast, artifacts, depiction of lesions) by two investigators and contrast-to-noise ratios (CNR) were compared using the Student's t-test. The image quality and CNR in the HR-FS were significantly superior compared to the HR-SS for both contrast agents (p < 0.05). The CNR was also improved when using the blood pool agent but only to a minor extent while the subjective image quality was similar for both contrast agents. Conclusion: The utilized sequence with water-selective excitation improved image quality and CNR properties in high spatial resolution imaging of brain arteries and veins. The used blood pool contrast agent improved the CNR only to a minor extent over the extracellular contrast agent. (orig.)

  8. Deep Brain Stimulation Target Selection in an Advanced Parkinson's Disease Patient with Significant Tremor and Comorbid Depression

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    Amar S. Patel

    2017-04-01

    Full Text Available Clinical Vignette: A 67-year-old female with advanced Parkinson's disease (PD, medically refractory tremor, and a history of significant depression presents for evaluation of deep brain stimulation (DBS candidacy.  Clinical Dilemma: Traditionally, stimulation of the subthalamic nucleus (STN has been the preferred target for patients with significant PD tremor. However, STN stimulation is avoided in patients with a significant pre-surgical history of mood disorder.  Clinical Solution: Bilateral DBS of the globus pallidus interna led to significant short term improvement in PD motor symptoms, including significant tremor reduction.  Gap in Knowledge: There is insufficient evidence to support or refute clinicians' traditional preference for STN stimulation in treating refractory PD tremor. Similarly, the available evidence for risk of worsening depression and/or suicidality after STN DBS is mixed. Both questions require further clarification to guide patient and clinician decision-making.

  9. Beyond time and space: The effect of a lateralized sustained attention task and brain stimulation on spatial and selective attention.

    Science.gov (United States)

    Shalev, Nir; De Wandel, Linde; Dockree, Paul; Demeyere, Nele; Chechlacz, Magdalena

    2017-10-03

    The Theory of Visual Attention (TVA) provides a mathematical formalisation of the "biased competition" account of visual attention. Applying this model to individual performance in a free recall task allows the estimation of 5 independent attentional parameters: visual short-term memory (VSTM) capacity, speed of information processing, perceptual threshold of visual detection; attentional weights representing spatial distribution of attention (spatial bias), and the top-down selectivity index. While the TVA focuses on selection in space, complementary accounts of attention describe how attention is maintained over time, and how temporal processes interact with selection. A growing body of evidence indicates that different facets of attention interact and share common neural substrates. The aim of the current study was to modulate a spatial attentional bias via transfer effects, based on a mechanistic understanding of the interplay between spatial, selective and temporal aspects of attention. Specifically, we examined here: (i) whether a single administration of a lateralized sustained attention task could prime spatial orienting and lead to transferable changes in attentional weights (assigned to the left vs right hemi-field) and/or other attentional parameters assessed within the framework of TVA (Experiment 1); (ii) whether the effects of such spatial-priming on TVA parameters could be further enhanced by bi-parietal high frequency transcranial random noise stimulation (tRNS) (Experiment 2). Our results demonstrate that spatial attentional bias, as assessed within the TVA framework, was primed by sustaining attention towards the right hemi-field, but this spatial-priming effect did not occur when sustaining attention towards the left. Furthermore, we show that bi-parietal high-frequency tRNS combined with the rightward spatial-priming resulted in an increased attentional selectivity. To conclude, we present a novel, theory-driven method for attentional modulation

  10. Kinetic analysis of [11C]befloxatone in the human brain, a selective radioligand to image monoamine oxidase A.

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    Zanotti-Fregonara, Paolo; Leroy, Claire; Roumenov, Dimitri; Trichard, Christian; Martinot, Jean-Luc; Bottlaender, Michel

    2013-11-25

    [11C]Befloxatone measures the density of the enzyme monoamine oxidase A (MAO-A) in the brain. MAO-A is responsible for the degradation of different neurotransmitters and is implicated in several neurologic and psychiatric illnesses. This study sought to estimate the distribution volume (VT) values of [11C]befloxatone in humans using an arterial input function. Seven healthy volunteers were imaged with positron emission tomography (PET) after [11C]befloxatone injection. Kinetic analysis was performed using an arterial input function in association with compartmental modeling and with the Logan plot, multilinear analysis (MA1), and standard spectral analysis (SA) at both the regional and voxel level. Arterialized venous samples were drawn as an alternative and less invasive input function. An unconstrained two-compartment model reliably quantified VT values in large brain regions. A constrained model did not significantly improve VT identifiability. Similar VT results were obtained using SA; however, the Logan plot and MA1 slightly underestimated VT values (about -10%). At the voxel level, SA showed a very small bias (+2%) compared to compartmental modeling, Logan severely underestimated VT values, and voxel-wise images obtained with MA1 were too noisy to be reliably quantified. Arterialized venous blood samples did not provide a satisfactory alternative input function as the Logan-VT regional values were not comparable to those obtained with arterial sampling in all subjects. Binding of [11C]befloxatone to MAO-A can be quantified using an arterial input function and a two-compartment model or, in parametric images, with SA.

  11. Differential Expression of FosB Proteins and Potential Target Genes in Select Brain Regions of Addiction and Depression Patients.

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    Paula A Gajewski

    Full Text Available Chronic exposure to stress or drugs of abuse has been linked to altered gene expression throughout the body, and changes in gene expression in discrete brain regions are thought to underlie many psychiatric diseases, including major depressive disorder and drug addiction. Preclinical models of these disorders have provided evidence for mechanisms of this altered gene expression, including transcription factors, but evidence supporting a role for these factors in human patients has been slow to emerge. The transcription factor ΔFosB is induced in the prefrontal cortex (PFC and hippocampus (HPC of rodents in response to stress or cocaine, and its expression in these regions is thought to regulate their "top down" control of reward circuitry, including the nucleus accumbens (NAc. Here, we use biochemistry to examine the expression of the FosB family of transcription factors and their potential gene targets in PFC and HPC postmortem samples from depressed patients and cocaine addicts. We demonstrate that ΔFosB and other FosB isoforms are downregulated in the HPC but not the PFC in the brains of both depressed and addicted individuals. Further, we show that potential ΔFosB transcriptional targets, including GluA2, are also downregulated in the HPC but not PFC of cocaine addicts. Thus, we provide the first evidence of FosB gene expression in human HPC and PFC in these psychiatric disorders, and in light of recent findings demonstrating the critical role of HPC ΔFosB in rodent models of learning and memory, these data suggest that reduced ΔFosB in HPC could potentially underlie cognitive deficits accompanying chronic cocaine abuse or depression.

  12. Interleukin-1 interaction with neuroregulatory systems: selective enhancement by recombinant human and mouse interleukin-1 of in vitro opioid peptide receptor binding in rat brain

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    Wiedermann, C.J.

    1989-02-01

    Interleukin-1 (IL-1) exerts a wide variety of biological effects on various cell types and may be regarded as a pleiotropic peptide hormone. Biological evidence suggests that IL-1 participates in the modulation of central nervous system physiology and behavior in a fashion characteristic of neuroendocrine hormones. In this investigation, recombinant (r) human (h) IL-1 and r mouse (m) IL-1 were examined for their modulation of opioid peptide receptor binding in vitro. Experiments were performed on frozen sections of rat brain. Receptor binding of radiolabeled substance P and of radiolabeled neurotensin were not significantly affected by the presence of rIL-1s. Recombinant IL-1s, however, significantly enhanced specific binding of 125I-beta-endorphin (125I-beta-END) and of D-ala2-(tyrosyl-3,5-3H)enkephalin-(5-D-leucine) (3H-D-ALA), equipotently and in a concentration-dependent manner with maximal activity occurring at a concentration of 10 LAF units/ml. The increased binding of 125I-beta-END and 3H-D-ALA was blocked steroselectively by (-)-naloxone and by etorphine, suggesting detection of opiate receptors. In addition, brain distribution patterns of receptors labeled in the presence of rIL-1s corresponded to patterns previously published for opiate receptors. Autoradiographic visualization of receptors revealed that rIL-1s in the different areas of the brain exert their effect on opioid binding with comparable potencies. The data suggest that certain central nervous system effects of IL-1s may be mediated by their selective interaction with opiatergic systems at the receptor level.

  13. Selective plane illumination microscopy (SPIM) with time-domain fluorescence lifetime imaging microscopy (FLIM) for volumetric measurement of cleared mouse brain samples

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    Funane, Tsukasa; Hou, Steven S.; Zoltowska, Katarzyna Marta; van Veluw, Susanne J.; Berezovska, Oksana; Kumar, Anand T. N.; Bacskai, Brian J.

    2018-05-01

    We have developed an imaging technique which combines selective plane illumination microscopy with time-domain fluorescence lifetime imaging microscopy (SPIM-FLIM) for three-dimensional volumetric imaging of cleared mouse brains with micro- to mesoscopic resolution. The main features of the microscope include a wavelength-adjustable pulsed laser source (Ti:sapphire) (near-infrared) laser, a BiBO frequency-doubling photonic crystal, a liquid chamber, an electrically focus-tunable lens, a cuvette based sample holder, and an air (dry) objective lens. The performance of the system was evaluated with a lifetime reference dye and micro-bead phantom measurements. Intensity and lifetime maps of three-dimensional human embryonic kidney (HEK) cell culture samples and cleared mouse brain samples expressing green fluorescent protein (GFP) (donor only) and green and red fluorescent protein [positive Förster (fluorescence) resonance energy transfer] were acquired. The results show that the SPIM-FLIM system can be used for sample sizes ranging from single cells to whole mouse organs and can serve as a powerful tool for medical and biological research.

  14. Controlling selective stimulations below a spinal cord hemisection using brain recordings with a neural interface system approach

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    Panetsos, Fivos; Sanchez-Jimenez, Abel; Torets, Carlos; Largo, Carla; Micera, Silvestro

    2011-08-01

    In this work we address the use of realtime cortical recordings for the generation of coherent, reliable and robust motor activity in spinal-lesioned animals through selective intraspinal microstimulation (ISMS). The spinal cord of adult rats was hemisectioned and groups of multielectrodes were implanted in both the central nervous system (CNS) and the spinal cord below the lesion level to establish a neural system interface (NSI). To test the reliability of this new NSI connection, highly repeatable neural responses recorded from the CNS were used as a pattern generator of an open-loop control strategy for selective ISMS of the spinal motoneurons. Our experimental procedure avoided the spontaneous non-controlled and non-repeatable neural activity that could have generated spurious ISMS and the consequent undesired muscle contractions. Combinations of complex CNS patterns generated precisely coordinated, reliable and robust motor actions.

  15. Potent and Selective Triazole-Based Inhibitors of the Hypoxia-Inducible Factor Prolyl-Hydroxylases with Activity in the Murine Brain.

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    Mun Chiang Chan

    Full Text Available As part of the cellular adaptation to limiting oxygen availability in animals, the expression of a large set of genes is activated by the upregulation of the hypoxia-inducible transcription factors (HIFs. Therapeutic activation of the natural human hypoxic response can be achieved by the inhibition of the hypoxia sensors for the HIF system, i.e. the HIF prolyl-hydroxylases (PHDs. Here, we report studies on tricyclic triazole-containing compounds as potent and selective PHD inhibitors which compete with the 2-oxoglutarate co-substrate. One compound (IOX4 induces HIFα in cells and in wildtype mice with marked induction in the brain tissue, revealing that it is useful for studies aimed at validating the upregulation of HIF for treatment of cerebral diseases including stroke.

  16. Injury severity and disability in the selection of next level of care following acute medical treatment for traumatic brain injury.

    Science.gov (United States)

    Malec, James F; Mandrekar, Jayawant N; Brown, Allen W; Moessner, Anne M

    2009-01-01

    To evaluate the association of demographic factors, post-traumatic amnesia (PTA) and a standardized measure of ability limitations with clinical decisions for Next Level of Care following acute hospital treatment for moderate-severe traumatic brain injury (TBI). A TBI Clinical Nurse specialist recorded PTA for 212 individuals and rated 159 on the Ability and Adjustment Indices of the Mayo-Portland Adaptability Inventory (MPAI-4) for comparison with clinical decisions. Multivariate logistic regression analyses revealed that independent ratings on the MPAI-4 Ability Index and PTA were associated with the clinical decision to admit to Inpatient Rehabilitation vs discharge to Home in 92.7% of the sample; ratings on the Ability Index alone were associated with this decision in 92.2% of cases. Age over 65 was the only variable associated with discharge to a Skilled Nursing Facility, correctly predicting this decision in 64% of cases. Use of a standardized measure of ability limitations appears feasible to provide supportive documentation and potentially improve the consistency of decision-making in recommending Inpatient Rehabilitation vs discharge to Home. Although age is a significant factor in the decision to discharge to a Skilled Nursing Facility, this decision appears complex and merits further study.

  17. Gene expression analysis in gonads and brain of catfish Clarias batrachus after the exposure of malathion.

    Science.gov (United States)

    Prathibha, Y; Murugananthkumar, R; Rajakumar, A; Laldinsangi, C; Sudhakumari, C C; Mamta, S K; Dutta-Gupta, A; Senthilkumaran, B

    2014-04-01

    Pesticides like malathion have the potential to disrupt development and reproduction of aquatic organisms including fishes. To investigate the likely consequences of malathion exposure at low doses in juvenile catfish, Clarias batrachus, we studied the expression pattern of genes encoding certain transcription factors, activin A, sex steroid or orphan nuclear receptors and steroidogenic enzymes which are known to be involved in gonadal development along with histological changes. To compare further, we also analyzed certain brain specific genes related to gonadal axis. Fifty days post hatch catfish fingerlings were exposed continuously to 1 and 10 µg/L of malathion for 21 days. Results from these experiments indicated that transcript levels of various genes were altered by the treatments, which may further affect the gonadal development either directly or indirectly through brain. Histological analysis revealed slow progression of spermatogenesis in testis, while in ovary, the oil droplet oocytes were found to be higher after treatment (10 µg/L). Our findings revealed that the exposure of malathion, even at low doses, hinder or modulate early gonadal development differentially by targeting gene expression pattern of transcription factors, activin A, sex steroid or orphan nuclear receptors and steroidogenic enzymes with an evidence on histological changes. Further, some of the genes showed differential expression at the level of brain in male and female sex after the exposure of malathion. Copyright © 2014. Published by Elsevier Inc.

  18. Computer aided diagnosis system for Alzheimer disease using brain diffusion tensor imaging features selected by Pearson's correlation.

    Science.gov (United States)

    Graña, M; Termenon, M; Savio, A; Gonzalez-Pinto, A; Echeveste, J; Pérez, J M; Besga, A

    2011-09-20

    The aim of this paper is to obtain discriminant features from two scalar measures of Diffusion Tensor Imaging (DTI) data, Fractional Anisotropy (FA) and Mean Diffusivity (MD), and to train and test classifiers able to discriminate Alzheimer's Disease (AD) patients from controls on the basis of features extracted from the FA or MD volumes. In this study, support vector machine (SVM) classifier was trained and tested on FA and MD data. Feature selection is done computing the Pearson's correlation between FA or MD values at voxel site across subjects and the indicative variable specifying the subject class. Voxel sites with high absolute correlation are selected for feature extraction. Results are obtained over an on-going study in Hospital de Santiago Apostol collecting anatomical T1-weighted MRI volumes and DTI data from healthy control subjects and AD patients. FA features and a linear SVM classifier achieve perfect accuracy, sensitivity and specificity in several cross-validation studies, supporting the usefulness of DTI-derived features as an image-marker for AD and to the feasibility of building Computer Aided Diagnosis systems for AD based on them. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Long-term feeding of hydroalcoholic extract powder of Lepidium meyenii (maca) enhances the steroidogenic ability of Leydig cells to alleviate its decline with ageing in male rats.

    Science.gov (United States)

    Yoshida, K; Ohta, Y; Kawate, N; Takahashi, M; Inaba, T; Hatoya, S; Morii, H; Takahashi, K; Ito, M; Tamada, H

    2018-02-01

    This study examined whether feeding hydroalcoholic extract of Lepidium meyenii (maca) to 8-week-old (sexually maturing) or 18-week-old (mature) male rats for more than a half year affects serum testosterone concentration and testosterone production by Leydig cells cultured with hCG, 22R-hydroxycholesterol or pregnenolone. Testosterone concentration was determined in the serum samples obtained before and 6, 12, 18 and 24 weeks after the feeding, and it was significantly increased only at the 6 weeks in the group fed with the maca extract to maturing rats when it was compared with controls. Testosterone production by Leydig cells significantly increased when cultured with hCG by feeding the maca extract to maturing rats for 27 weeks (35 weeks of age) and when cultured with 22R-hydroxycholesterol by feeding it to mature rats for 30 weeks (48 weeks of age). Overall testosterone production by cultured Leydig cells decreased to about a half from 35 to 48 weeks of age. These results suggest that feeding the maca extract for a long time to male rats may enhance the steroidogenic ability of Leydig cells to alleviate its decline with ageing, whereas it may cause only a transient increase in blood testosterone concentration in sexually maturing male rats. © 2017 Blackwell Verlag GmbH.

  20. Lysosomes are involved in induction of steroidogenic acute regulatory protein (StAR) gene expression and progesterone synthesis through low-density lipoprotein in cultured bovine granulosa cells.

    Science.gov (United States)

    Zhang, Jin-You; Wu, Yi; Zhao, Shuan; Liu, Zhen-Xing; Zeng, Shen-Ming; Zhang, Gui-Xue

    2015-09-15

    Progesterone is an important steroid hormone in the regulation of the bovine estrous cycle. The steroidogenic acute regulatory protein (StAR) is an indispensable component for transporting cholesterol to the inner mitochondrial membrane, which is one of the rate-limiting steps for progesterone synthesis. Low-density lipoprotein (LDL) supplies cholesterol precursors for progesterone formation, and the lysosomal degradation pathway of LDL is essential for progesterone biosynthesis in granulosa cells after ovulation. However, it is currently unknown how LDL and lysosomes coordinate the expression of the StAR gene and progesterone production in bovine granulosa cells. Here, we investigated the role of lysosomes in LDL-treated bovine granulosa cells. Our results reported that LDL induced expression of StAR messenger RNA and protein as well as expression of cholesterol side-chain cleavage cytochrome P-450 (CYP11A1) messenger RNA and progesterone production in cultured bovine granulosa cells. The number of lysosomes in the granulosa cells was also significantly increased by LDL; whereas the lysosomal inhibitor, chloroquine, strikingly abolished these LDL-induced effects. Our results indicate that LDL promotes StAR expression, synthesis of progesterone, and formation of lysosomes in bovine granulosa cells, and lysosomes participate in the process by releasing free cholesterol from hydrolyzed LDL. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Assessment of degradation of the selected projectile, commissural and association brain fibers in patients with Alzheimers disease on diffusion tensor MR imaging

    International Nuclear Information System (INIS)

    Szewczyk, P.; Zimny, A.; Sasiadek, M.; Trypka, E.; Wojtynska, R.; Leszek, J.

    2010-01-01

    Background: Pathological examinations and the increasingly popular diffusion tensor imaging (DTI) show that in Alzheimers disease (AD), the pathology involves not only the cortical and hippocampal structures, but also the white matter of the brain. DTI is a well recognized technique for evaluation of the integrity of white matter fibers. The aim of this study was to assess with the use of DTI some selected brain tracts in patients with AD, as well as to analyze the severity and distribution of the identified changes. Material/Methods: Thirty-five patients with AD (mean age of 71.6 years, MMSE 17.6), and a control group of 15 healthy volunteers (mean age of 69.1 years, MMSE 29.8) were enrolled in the study. All patients were subjected to a thorough psychiatric examination and psychological tests. DTI examinations (TE 8500, TR 100) were performed using a 1.5 T MR scanner. Fractional anisotropy (FA) measurements in the selected areas of interest (ROI) of the white matter fibers were performed under the control of color FA maps. The following fibers were evaluated - the middle cerebellar peduncles (MCP), the inferior longitudinal fasciculi (ILF), inferior frontooccipital fasciculi (IFO), genu (GCC) and splenium of the corpus callosum (SCC), posterior limbs of internal capsules (PLIC), superior longitudinal fasciculi (SLF) and posterior cingula (CG). Results: There was a statistically significant decrease in FA in patients with AD, comparing to the control group. It was particularly strongly expressed in both CG (P < 0.0001), followed by both ILF, right IFO, and left SLF. Less pronounced changes were found in GCC, SCC, and left IFO. In both PLICs and MCPs and in the right SLF, there was no significant change of FA. Conclusions: In Alzheimers disease, there is a significant decrease in FA, which suggests degradation of the majority of the assessed white matter tracts. Distribution of these changes is not uniform. They involve the selected association fibers mainly and

  2. Domain-General Brain Regions Do Not Track Linguistic Input as Closely as Language-Selective Regions.

    Science.gov (United States)

    Blank, Idan A; Fedorenko, Evelina

    2017-10-11

    Language comprehension engages a cortical network of left frontal and temporal regions. Activity in this network is language-selective, showing virtually no modulation by nonlinguistic tasks. In addition, language comprehension engages a second network consisting of bilateral frontal, parietal, cingulate, and insular regions. Activity in this "multiple demand" (MD) network scales with comprehension difficulty, but also with cognitive effort across a wide range of nonlinguistic tasks in a domain-general fashion. Given the functional dissociation between the language and MD networks, their respective contributions to comprehension are likely distinct, yet such differences remain elusive. Prior neuroimaging studies have suggested that activity in each network covaries with some linguistic features that, behaviorally, influence on-line processing and comprehension. This sensitivity of the language and MD networks to local input characteristics has often been interpreted, implicitly or explicitly, as evidence that both networks track linguistic input closely, and in a manner consistent across individuals. Here, we used fMRI to directly test this assumption by comparing the BOLD signal time courses in each network across different people ( n = 45, men and women) listening to the same story. Language network activity showed fewer individual differences, indicative of closer input tracking, whereas MD network activity was more idiosyncratic and, moreover, showed lower reliability within an individual across repetitions of a story. These findings constrain cognitive models of language comprehension by suggesting a novel distinction between the processes implemented in the language and MD networks. SIGNIFICANCE STATEMENT Language comprehension recruits both language-specific mechanisms and domain-general mechanisms that are engaged in many cognitive processes. In the human cortex, language-selective mechanisms are implemented in the left-lateralized "core language network

  3. Novel approach for independent control of brain hypothermia and systemic normothermia: cerebral selective deep hypothermia for refractory cardiac arrest.

    Science.gov (United States)

    Wang, Chih-Hsien; Lin, Yu-Ting; Chou, Heng-Wen; Wang, Yi-Chih; Hwang, Joey-Jen; Gilbert, John R; Chen, Yih-Sharng

    2017-08-01

    A 38-year-old man was found unconscious, alone in the driver's seat of his car. The emergency medical team identified his condition as pulseless ventricular tachycardia. Defibrillation was attempted but failed. Extracorporeal membrane oxygenation (ECMO) was started in the emergency room 52 min after the estimated arrest following the extracorporeal cardiopulmonary resuscitation (ECPR) protocol in our center. The initial prognosis under the standard protocol was <25% chance of survival. A novel adjunctive to our ECPR protocol, cerebral selective deep (<30°C) hypothermia (CSDH), was applied. CSDH adds a second independent femoral access extracorporeal circuit, perfusing cold blood into the patient's common carotid artery. The ECMO and CSDH circuits demonstrated independent control of cerebral and core temperatures. Nasal temperature was lowered to below 30°C for 12 hours while core was maintained at normothermia. The patient was discharged without significant neurological deficit 32 days after the initial arrest. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Selection of TI for Suppression Fat Tissue of SPAIR and Comparative Study of SPAIR and STIR of Brain Fast SE T2 Weighted Imaging

    International Nuclear Information System (INIS)

    Lee, Hoo Min; Kim, Ham Gyum; Kong, Seok Kyo

    2009-01-01

    The purpose of this research is to seek SPAIR's reversal time (TI) which satisfies two conditions ; maintaining the suppression ability of fat tissue and simultaneously minimizing the inhomogeneity of fat tissue in T2 high-speed spin echo 3.0T magnetic resonance image (MRI) of the brain, and to compare SPAIR with STIR which is fat-suppression technique. The reversal times (TI) of SPAIR protocol are set to 1/2, 1/3, 1/6 and 1/12 of SPAIR TR (420 msec), namely 210 msec (8 people), 140 msec (26 people), 70 msec (26 people) and 35 msec (18 people) and STIR TI is set with 250 msec (26 people). With these parameter sets, we acquired the axis direction 104 images of the brain. In ROI (50 mm 2 ) of output image, signal intensities of the fatty tissue, the muscular tissue, and the background were measured and the CNRs of fatty tissue and the muscular tissue were calculated. The inhomogeneity of the fatty tissue is SD/mean, where SD is the standard deviation and 'mean' is a average fatty tissue signal. Consequently, SPAIR TI is determined on either 1/3 or 1/6 of TR (420 ms) ; 140 ms or 70 ms. Because the difference of statistics in fat-suppression ability and inhomogeneity of fatty tissue is very small (p < 0.001), Selecting 140 ms seems to be better choice for the image quality. Meanwhile, Comparing SPAIR (TI : 140 ms) with STIR, the fat-suppression is not able to be considered statistically (p < 0.252), but the image quality is able to be considered statistically (p < 0.01). In conclusion, SPAIR is better than STIR in the image quality.

  5. A biphasic and brain-region selective down-regulation of cyclic adenosine monophosphate concentrations supports object recognition in the rat.

    Directory of Open Access Journals (Sweden)

    Maïte Hotte

    Full Text Available BACKGROUND: We aimed to further understand the relationship between cAMP concentration and mnesic performance. METHODS AND FINDINGS: Rats were injected with milrinone (PDE3 inhibitor, 0.3 mg/kg, i.p., rolipram (PDE4 inhibitor, 0.3 mg/kg, i.p. and/or the selective 5-HT4R agonist RS 67333 (1 mg/kg, i.p. before testing in the object recognition paradigm. Cyclic AMP concentrations were measured in brain structures linked to episodic-like memory (i.e. hippocampus, prefrontal and perirhinal cortices before or after either the sample or the testing phase. Except in the hippocampus of rolipram treated-rats, all treatment increased cAMP levels in each brain sub-region studied before the sample phase. After the sample phase, cAMP levels were significantly increased in hippocampus (1.8 fold, prefrontal (1.3 fold and perirhinal (1.3 fold cortices from controls rat while decreased in prefrontal cortex (∼0.83 to 0.62 fold from drug-treated rats (except for milrinone+RS 67333 treatment. After the testing phase, cAMP concentrations were still increased in both the hippocampus (2.76 fold and the perirhinal cortex (2.1 fold from controls animals. Minor increase were reported in hippocampus and perirhinal cortex from both rolipram (respectively, 1.44 fold and 1.70 fold and milrinone (respectively 1.46 fold and 1.56 fold-treated rat. Following the paradigm, cAMP levels were significantly lower in the hippocampus, prefrontal and perirhinal cortices from drug-treated rat when compared to controls animals, however, only drug-treated rats spent longer time exploring the novel object during the testing phase (inter-phase interval of 4 h. CONCLUSIONS: Our results strongly suggest that a "pre-sample" early increase in cAMP levels followed by a specific lowering of cAMP concentrations in each brain sub-region linked to the object recognition paradigm support learning efficacy after a middle-term delay.

  6. [3H]CGS 21680, a selective A2 adenosine receptor agonist directly labels A2 receptors in rat brain

    International Nuclear Information System (INIS)

    Jarvis, M.F.; Schulz, R.; Hutchison, A.J.; Do, U.H.; Sills, M.A.; Williams, M.

    1989-01-01

    In the present study, the binding of a highly A2-selective agonist radioligand, [3H]CGS 21680 (2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido adenosine) is described. [3H]CGS 21680 specific binding to rat striatal membranes was saturable, reversible and dependent upon protein concentration. Saturation studies revealed that [3H]CGS 21680 bound with high affinity (Kd = 15.5 nM) and limited capacity (apparent Bmax = 375 fmol/mg of protein) to a single class of recognition sites. Estimates of ligand affinity (16 nM) determined from association and dissociation kinetic experiments were in close agreement with the results from the saturation studies. [3H]CGS 21680 binding was greatest in striatal membranes with negligible specific binding obtained in rat cortical membranes. Adenosine agonists ligands competed for the binding of 5 nM [3H]CGS 21680 to striatal membranes with the following order of activity; CGS 21680 = 5'-N-ethylcarboxamidoadenosine greater than 2-phenylaminoadenosine (CV-1808) = 5'-N-methylcarboxamidoadenosine = 2-chloroadenosine greater than R-phenylisopropyladenosine greater than N6-cyclohexyladenosine greater than N6cyclopentyltheophylline greater than S-phenylisopropyladenosine. The nonxanthine adenosine antagonist, CGS 15943A, was the most active compound in inhibiting the binding of [3H]CGS 21680. Other adenosine antagonists inhibited binding in the following order; xanthine amine congener = 1,3-dipropyl-8-(2-amino-4-chloro)phenylxanthine greater than 1,3-dipropyl-8-cyclopentylxanthine greater than 1,3-diethyl-8-phenylxanthine greater than 8-phenyltheophylline greater than 8-cyclopentyltheophylline = xanthine carboxylic acid congener greater than 8-parasulfophenyltheophylline greater than theophylline greater than caffeine

  7. [11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain

    International Nuclear Information System (INIS)

    Halldin, Christer; Erixon-Lindroth, Nina; Pauli, Stefan; Chou, Yuan-Hwa; Okubo, Yoshiro; Karlsson, Per; Lundkvist, Camilla; Olsson, Hans; Farde, Lars; Guilloteau, Denis; Emond, Patrick

    2003-01-01

    The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [ 11 C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/μmol). [ 11 C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55-65 min after injection. Displacement and pretreatment measurements using unlabelled β-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [ 11 C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40-50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [ 11 C]PE2I was 15-20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [ 11 C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. (orig.)

  8. [{sup 11}C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain

    Energy Technology Data Exchange (ETDEWEB)

    Halldin, Christer; Erixon-Lindroth, Nina; Pauli, Stefan; Chou, Yuan-Hwa; Okubo, Yoshiro; Karlsson, Per; Lundkvist, Camilla; Olsson, Hans; Farde, Lars [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 17176, Stockholm (Sweden); Guilloteau, Denis; Emond, Patrick [INSERM U316 Universite Francois Rabelais, Tours (France)

    2003-09-01

    The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2{beta}-carbomethoxy-3{beta}-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [{sup 11}C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/{mu}mol). [{sup 11}C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55-65 min after injection. Displacement and pretreatment measurements using unlabelled {beta}-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [{sup 11}C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40-50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [{sup 11}C]PE2I was 15-20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [{sup 11}C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. (orig.)

  9. Survival Rate without Brain Abnormalities on Postnatal Ultrasonography among Monochorionic Twins after Fetoscopic Laser Photocoagulation for Selective Intrauterine Growth Restriction with Concomitant Oligohydramnios.

    Science.gov (United States)

    Ishii, Keisuke; Wada, Seiji; Takano, Mayumi; Nakata, Masahiko; Murakoshi, Takeshi; Sago, Haruhiko

    2018-02-20

    We aimed to clarify the survival rate without brain abnormalities (BA) after fetoscopic laser photoco-agulation (FLP) for monochorionic diamniotic twin gestations (MCDA) with selective intrauterine growth restriction (sIUGR) accompanied by abnormal umbilical artery (UA) Doppler waveforms and isolated oligohydramnios in the sIUGR twin. This retrospective study included 52 cases that underwent FLP. The main outcome was survival rate without BA of the twins at age 28 days. BA was defined as severe intraventricular hemorrhage and periventricular leukomalacia on postnatal ultrasonography. Median gestational age at FLP was 20 (16-24) weeks. Ten cases were classified as type III based on Doppler for the UA. For all cases, including 20 cases of anterior placenta, FLP was completed without major intraoperative complications. Amnioinfusion was required in 49 cases for better fetoscopic visualization. Fetal loss occurred in 29 sIUGR twins and two larger twins, whereas one larger twin experienced neonatal death. Survival rates without BA were 44% (n = 23) for sIUGR twins and 94% (n = 49) for the larger twins. FLP for MCDA with sIUGR presenting with oligohydramnios in the sIUGR twin might be considered a prenatal treatment option. © 2018 S. Karger AG, Basel.

  10. MS-377, a novel selective sigma(1) receptor ligand, reverses phencyclidine-induced release of dopamine and serotonin in rat brain.

    Science.gov (United States)

    Takahashi, S; Horikomi, K; Kato, T

    2001-09-21

    A novel selective sigma(1) receptor ligand, (R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl)piperazin-1-yl]methyl-2-pyrrolidinone L-tartrate (MS-377), inhibits phencyclidine (1-(1-phenylcyclohexyl)piperidine; PCP)-induced behaviors in animal models. In this study, we measured extracellular dopamine and serotonin levels in the rat brain after treatment with MS-377 alone, using in vivo microdialysis. We also examined the effects of MS-377 on extracellular dopamine and serotonin levels in the rat medial prefrontal cortex after treatment with PCP. MS-377 itself had no significant effects on dopamine release in the striatum (10 mg/kg, p.o.) nor on dopamine or serotonin release in the medial prefrontal cortex (1 and 10 mg/kg, p.o.). PCP (3 mg/kg, i.p.) markedly increased dopamine and serotonin release in the medial prefrontal cortex. MS-377 (1 mg/kg, p.o.), when administered 60 min prior to PCP, significantly attenuated this effect of PCP. These results suggest that the inhibitory effects of MS-377 on PCP-induced behaviors are partly mediated by inhibition of the increase in dopamine and serotonin release in the rat medial prefrontal cortex caused by PCP.

  11. Imaging dopamine D3 receptors in the human brain with positron emission tomography, [11C]PHNO, and a selective D3 receptor antagonist.

    Science.gov (United States)

    Searle, Graham; Beaver, John D; Comley, Robert A; Bani, Massimo; Tziortzi, Andri; Slifstein, Mark; Mugnaini, Manolo; Griffante, Cristiana; Wilson, Alan A; Merlo-Pich, Emilio; Houle, Sylvain; Gunn, Roger; Rabiner, Eugenii A; Laruelle, Marc

    2010-08-15

    Dopamine D(3) receptors are involved in the pathophysiology of several neuropsychiatric conditions. [(11)C]-(+)-PHNO is a radiolabeled D(2) and D(3) agonist, suitable for imaging the agonist binding sites (denoted D(2HIGH) and D(3)) of these receptors with positron emission tomography (PET). PET studies in nonhuman primates documented that, in vivo, [(11)C]-(+)-PHNO displays a relative selectivity for D(3) compared with D(2HIGH) receptor sites and that the [(11)C]-(+)-PHNO signal is enriched in D(3) contribution compared with conventional ligands such as [(11)C] raclopride. To define the D(3) contribution (f(PHNO)(D3)) to [(11)C]-(+)-PHNO binding potential (BP(ND)) in healthy humans, 52 PET scans were obtained in 19 healthy volunteers at baseline and following oral administration of various doses of the selective D(3) receptor antagonist, GSK598809. The impact of GSK598809 on [(11)C]-(+)-PHNO was regionally selective. In dorsal regions of the striatum, GSK598809 did not significantly affect [(11)C]-(+)-PHNO BP(ND) (f(PHNO)(D3) approximately 0%). Conversely, in the substantia nigra, GSK598809 dose-dependently reduced [(11)C]-(+)-PHNO binding to nonspecific level (f(PHNO)(D3) approximately 100%). In ventral striatum (VST), globus pallidus and thalamus (THA), [(11)C]-(+)-PHNO BP(ND) was attributable to a combination of D(2HIGH) and D(3) receptor sites, with f(PHNO)(D3) of 26%, 67% and 46%, respectively. D(3) receptor binding potential (BP(ND)(D3)) was highest in globus pallidus (1.90) and substantial nigra (1.39), with lower levels in VST (.77) and THA (.18) and negligible levels in dorsal striatum. This study elucidated the pharmacologic nature of the [(11)C]-(+)-PHNO signal in healthy subjects and provided the first quantification of D(3) receptor availability with PET in the living human brain. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Quantification of glutathione transverse relaxation time T2 using echo time extension with variable refocusing selectivity and symmetry in the human brain at 7 Tesla

    Science.gov (United States)

    Swanberg, Kelley M.; Prinsen, Hetty; Coman, Daniel; de Graaf, Robin A.; Juchem, Christoph

    2018-05-01

    Glutathione (GSH) is an endogenous antioxidant implicated in numerous biological processes, including those associated with multiple sclerosis, aging, and cancer. Spectral editing techniques have greatly facilitated the acquisition of glutathione signal in living humans via proton magnetic resonance spectroscopy, but signal quantification at 7 Tesla is still hampered by uncertainty about the glutathione transverse decay rate T2 relative to those of commonly employed quantitative references like N-acetyl aspartate (NAA), total creatine, or water. While the T2 of uncoupled singlets can be derived in a straightforward manner from exponential signal decay as a function of echo time, similar estimation of signal decay in GSH is complicated by a spin system that involves both weak and strong J-couplings as well as resonances that overlap those of several other metabolites and macromolecules. Here, we extend a previously published method for quantifying the T2 of GABA, a weakly coupled system, to quantify T2 of the strongly coupled spin system glutathione in the human brain at 7 Tesla. Using full density matrix simulation of glutathione signal behavior, we selected an array of eight optimized echo times between 72 and 322 ms for glutathione signal acquisition by J-difference editing (JDE). We varied the selectivity and symmetry parameters of the inversion pulses used for echo time extension to further optimize the intensity, simplicity, and distinctiveness of glutathione signals at chosen echo times. Pairs of selective adiabatic inversion pulses replaced nonselective pulses at three extended echo times, and symmetry of the time intervals between the two extension pulses was adjusted at one extended echo time to compensate for J-modulation, thereby resulting in appreciable signal-to-noise ratio and quantifiable signal shapes at all measured points. Glutathione signal across all echo times fit smooth monoexponential curves over ten scans of occipital cortex voxels in nine

  13. Brain herniation

    Science.gov (United States)

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  14. The selectivity and promiscuity of brain-neuroregenerative inhibitors between ROCK1 and ROCK2 isoforms: An integration of SB-QSSR modelling, QM/MM analysis and in vitro kinase assay.

    Science.gov (United States)

    Zhu, L; Yang, Y; Lu, X

    2016-01-01

    The Rho-associated kinases (ROCKs) have long been recognized as an attractive therapeutic target for various neurological diseases; selective inhibition of ROCK1 and ROCK2 isoforms would result in distinct biological effects on neurogenesis, neuroplasticity and neuroregeneration after brain surgery and traumatic brain injury. However, the discovery and design of isoform-selective inhibitors remain a great challenge due to the high conservation and similarity between the kinase domains of ROCK1 and ROCK2. Here, a structure-based quantitative structure-selectivity relationship (SB-QSSR) approach was used to correlate experimentally measured selectivity with the difference in inhibitor binding to the two kinase isoforms. The resulting regression models were examined rigorously through both internal cross-validation and external blind validation; a nonlinear predictor was found to have high fitting stability and strong generalization ability, which was then employed to perform virtual screening against a structurally diverse, drug-like compound library. Consequently, five and seven hits were identified as promising candidates of 1-o-2 and 2-o-1 selective inhibitors, respectively, from which seven purchasable compounds were tested in vitro using a standard kinase assay protocol to determine their inhibitory activity against and selectivity between ROCK1 and ROCK2. The structural basis, energetic property and biological implication underlying inhibitor selectivity and promiscuity were also investigated systematically using a hybrid quantum mechanics/molecular mechanics (QM/MM) scheme.

  15. Involvement of adenosine monophosphate activated kinase in interleukin-6 regulation of steroidogenic acute regulatory protein and cholesterol side chain cleavage enzyme in the bovine zona fasciculata and zona reticularis.

    Science.gov (United States)

    De Silva, Matharage S I; Dayton, Adam W; Rhoten, Lance R; Mallett, John W; Reese, Jared C; Squires, Mathieu D; Dalley, Andrew P; Porter, James P; Judd, Allan M

    2018-06-01

    In bovine adrenal zona fasciculata (ZF) and NCI-H295R cells, interleukin-6 (IL-6) increases cortisol release, increases expression of steroidogenic acute regulatory protein (StAR), cholesterol side chain cleavage enzyme (P450scc), and steroidogenic factor 1 (SF-1) (increases steroidogenic proteins), and decreases the expression of adrenal hypoplasia congenita-like protein (DAX-1) (inhibits steroidogenic proteins). In contrast, IL-6 decreases bovine adrenal zona reticularis (ZR) androgen release, StAR, P450scc, and SF-1 expression, and increases DAX-1 expression. Adenosine monophosphate (AMP) activated kinase (AMPK) regulates steroidogenesis, but its role in IL-6 regulation of adrenal steroidogenesis is unknown. In the present study, an AMPK activator (AICAR) increased (P < 0.01) NCI-H295R StAR promoter activity, StAR and P450scc expression, and the phosphorylation of AMPK (PAMPK) and acetyl-CoA carboxylase (PACC) (indexes of AMPK activity). In ZR (decreased StAR, P450scc, SF-1, increased DAX-1) (P < 0.01) and ZF tissues (increased StAR, P450scc, SF-1, decreased DAX-1) (P < 0.01), AICAR modified StAR, P450scc, SF-1 and DAX-1 mRNAs/proteins similar to the effects of IL-6. The activity (increased PAMPK and PACC) (P < 0.01) of AMPK in the ZF and ZR was increased by AICAR and IL-6. In support of an AMPK role in IL-6 ZF and ZR effects, the AMPK inhibitor compound C blocked (P < 0.01) the effects of IL-6 on the expression of StAR, P450scc, SF-1, and DAX-1. Therefore, IL-6 modification of the expression of StAR and P450scc in the ZF and ZR may involve activation of AMPK and these changes may be related to changes in the expression of SF-1 and DAX-1. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Optimization of ultra-performance liquid chromatography (UPLC) with fluorescence detector (FLD) method for the quantitative determination of selected neurotransmitters in rat brain.

    Science.gov (United States)

    Stragierowicz, Joanna; Daragó, Adam; Brzeźnicki, Sławomir; Kilanowicz, Anna

    2017-07-26

    Glutamate (Glu) and γ-aminobutyric acid (GABA) are the main neurotransmitters in the central nervous system for excitatory and inhibitory processes, respectively. Monitoring these neurotransmitters is an essential tool in establishing pathological functions, among others in terms of occupational exposure to toxic substances. We present modification of the HPLC (high-performance liquid chromatography) to the UPLC (ultra-performance liquid chromatography) method for the simultaneous determination of glutamate and γ-aminobutyric acid in a single injection. The isocratic separation of these neurotransmitter derivatives was performed on Waters Acquity BEH (ethylene bridged hybrid) C18 column with particle size of 1.7 μm at 35°C using a mobile phase consisting of 0.1 M acetate buffer (pH 6.0) and methanol (60:40, v/v) at a flow rate of 0.3 ml/min. The analytes were detected with the fluorescence detector (FLD) using derivatization with o-phthaldialdehyde (OPA), resulting in excitation at 340 nm and emission at 455 nm. Several validation parameters including linearity (0.999), accuracy (101.1%), intra-day precision (1.52-1.84%), inter-day precision (2.47-3.12%), limit of detection (5-30 ng/ml) and quantification (100 ng/ml) were examined. The developed method was also used for the determination of these neurotransmitters in homogenates of selected rat brain structures. The presented UPLC-FLD is characterized by shorter separation time (3.5 min), which is an adaptation of the similar HPLC methods and is an alternative for more expensive references techniques such as liquid chromatography coupled with tandem mass-spectrometry (LC-MS/MS) methods. Med Pr 2017;68(5):583-591. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  17. Selective labeling of serotonin uptake sites in rat brain by [3H]citalopram contrasted to labeling of multiple sites by [3H]imipramine

    International Nuclear Information System (INIS)

    D'Amato, R.J.; Largent, B.L.; Snowman, A.M.; Snyder, S.H.

    1987-01-01

    Citalopram is a potent and selective inhibitor of neuronal serotonin uptake. In rat brain membranes [ 3 H]citalopram demonstrates saturable and reversible binding with a KD of 0.8 nM and a maximal number of binding sites (Bmax) of 570 fmol/mg of protein. The drug specificity for [ 3 H]citalopram binding and synaptosomal serotonin uptake are closely correlated. Inhibition of [ 3 H]citalopram binding by both serotonin and imipramine is consistent with a competitive interaction in both equilibrium and kinetic analyses. The autoradiographic pattern of [ 3 H]citalopram binding sites closely resembles the distribution of serotonin. By contrast, detailed equilibrium-saturation analysis of [ 3 H]imipramine binding reveals two binding components, i.e., high affinity (KD = 9 nM, Bmax = 420 fmol/mg of protein) and low affinity (KD = 553 nM, Bmax = 8560 fmol/mg of protein) sites. Specific [ 3 H]imipramine binding, defined as the binding inhibited by 100 microM desipramine, is displaced only partially by serotonin. Various studies reveal that the serotonin-sensitive portion of binding corresponds to the high affinity sites of [ 3 H]imipramine binding whereas the serotonin-insensitive binding corresponds to the low affinity sites. Lesioning of serotonin neurons with p-chloroamphetamine causes a large decrease in [ 3 H]citalopram and serotonin-sensitive [ 3 H]imipramine binding with only a small effect on serotonin-insensitive [ 3 H]imipramine binding. The dissociation rate of [ 3 H]imipramine or [ 3 H]citalopram is not altered by citalopram, imipramine or serotonin up to concentrations of 10 microM. The regional distribution of serotonin sensitive [ 3 H]imipramine high affinity binding sites closely resembles that of [ 3 H]citalopram binding

  18. High Antifouling Property of Ion-Selective Membrane: toward In Vivo Monitoring of pH Change in Live Brain of Rats with Membrane-Coated Carbon Fiber Electrodes.

    Science.gov (United States)

    Hao, Jie; Xiao, Tongfang; Wu, Fei; Yu, Ping; Mao, Lanqun

    2016-11-15

    In vivo monitoring of pH in live brain remains very essential to understanding acid-base chemistry in various physiological processes. This study demonstrates a potentiometric method for in vivo monitoring of pH in the central nervous system with carbon fiber-based proton-selective electrodes (CF-H + ISEs) with high antifouling property. The CF-H + ISEs are prepared by formation of a H + -selective membrane (H + ISM) with polyvinyl chloride polymeric matrixes containing plasticizer bis(2-ethylhexyl)sebacate, H + ionophore tridodecylamine, and ion exchanger potassium tetrakis(4-chlorophenyl)borate onto carbon fiber electrodes (CFEs). Both in vitro and in vivo studies demonstrate that the H + ISM exhibits strong antifouling property against proteins, which enables the CF-H + ISEs to well maintain the sensitivity and reversibility for pH sensing after in vivo measurements. Moreover, the CF-H + ISEs exhibit a good response to pH changes within a narrow physiological pH range from 6.0 to 8.0 in quick response time with high reversibility and selectivity against species endogenously existing in the central nervous system. The applicability of the CF-H + ISEs is illustrated by real-time monitoring of pH changes during acid-base disturbances, in which the brain acidosis is induced by CO 2 inhalation and brain alkalosis is induced by bicarbonate injections. The results demonstrate that brain pH value rapidly decreases in the amygdaloid nucleus by ca. 0.14 ± 0.01 (n = 5) when the rats breath in pure CO 2 gas, while increases in the cortex by about 0.77 ± 0.12 (n = 3) following intraperitoneal injection of 5 mmol/kg NaHCO 3 . This study demonstrates a new potentiometric method for in vivo measurement of pH change in the live brain of rats with high reliability.

  19. Selection of reference genes for normalisation of real-time RT-PCR in brain-stem death injury in Ovis aries

    Directory of Open Access Journals (Sweden)

    Fraser John F

    2009-07-01

    Full Text Available Abstract Background Heart and lung transplantation is frequently the only therapeutic option for patients with end stage cardio respiratory disease. Organ donation post brain stem death (BSD is a pre-requisite, yet BSD itself causes such severe damage that many organs offered for donation are unusable, with lung being the organ most affected by BSD. In Australia and New Zealand, less than 50% of lungs offered for donation post BSD are suitable for transplantation, as compared with over 90% of kidneys, resulting in patients dying for lack of suitable lungs. Our group has developed a novel 24 h sheep BSD model to mimic the physiological milieu of the typical human organ donor. Characterisation of the gene expression changes associated with BSD is critical and will assist in determining the aetiology of lung damage post BSD. Real-time PCR is a highly sensitive method involving multiple steps from extraction to processing RNA so the choice of housekeeping genes is important in obtaining reliable results. Little information however, is available on the expression stability of reference genes in the sheep pulmonary artery and lung. We aimed to establish a set of stably expressed reference genes for use as a standard for analysis of gene expression changes in BSD. Results We evaluated the expression stability of 6 candidate normalisation genes (ACTB, GAPDH, HGPRT, PGK1, PPIA and RPLP0 using real time quantitative PCR. There was a wide range of Ct-values within each tissue for pulmonary artery (15–24 and lung (16–25 but the expression pattern for each gene was similar across the two tissues. After geNorm analysis, ACTB and PPIA were shown to be the most stably expressed in the pulmonary artery and ACTB and PGK1 in the lung tissue of BSD sheep. Conclusion Accurate normalisation is critical in obtaining reliable and reproducible results in gene expression studies. This study demonstrates tissue associated variability in the selection of these

  20. Curcumin and Quercetin Ameliorated Cypermethrin and Deltamethrin-Induced Reproductive System Impairment in Male Wistar Rats by Upregulating The Activity of Pituitary-Gonadal Hormones and Steroidogenic Enzymes

    Directory of Open Access Journals (Sweden)

    Poonam Sharma

    2018-01-01

    Full Text Available Background Dietary antioxidants protect tissues and organs against insecticides/xenobiotic-induced damage. In the present study, we evaluated the results of exposure to synthetic pyrethroid insecticides, cypermethrin (Cyp and deltamethrin (Del and possible protective effects of curcumin and quercetin on reproductive system in male Wistar rats. Materials and Methods In this controlled experimental study, 42 male Wistar rats were randomly divided into 7 groups of 6 animals. Group A served as control, group B was exposed to Cyp (2 mg/kg.bw, group C was exposed to Del (2 mg/kg.bw, group D was exposed to Cyp+Del (2 mg/kg.bw each, group E was exposed to Cyp+Del and treated with curcumin (100 mg/kg.bw, group F was exposed to Cyp+Del and treated with quercetin (100 mg/kg.bw and group G was exposed to Cyp+Del and treated with quercetin+curcumin for 45 days. Results Exposure to Cyp and Del caused decreases in reproductive organs weight, sperm count, sperm motility, level of sex hormones viz. testosterone (T, follicle stimulating hormone (FSH and luteinizing hormone (LH, steroidogenic enzymes viz. 3β-hydroxyl steroid dehydrogenase (3β-HSD and 17β-HSD, non-enzymatic antioxi- dant glutathione (GSH and enzymatic antioxidants viz. superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx, glutathione-S-transferase (GST and glutathione reductase (GR activity and increases in sperm abnormalities and lipid peroxidation (LPO. The exposure also adversely affected the histo-achitecture of testes. Single and combined treatment with curcumin and quercetin significantly ameliorated Cyp and Del-induced damage in reproductive system. Conclusion Curcumin and quercetin protected against Cyp and Del-induced reproductive system toxicity and oxidative damage in rats. The increases in activities of 3β-HSD and 17β-HSD with concomitant increases in testosterone were mainly responsible for ameliorating effects of curcumin and quercetin. Curcumin showed slightly

  1. Selected Abstracts of the 6th International Congress of UENPS; Valencia (Spain; November 23rd-25th 2016; Session “Brain and development”

    Directory of Open Access Journals (Sweden)

    --- Various Authors

    2016-11-01

    Full Text Available Selected Abstracts of the 6th International Congress of UENPS; Valencia (Spain; November 23rd-25th 2016; Session “Brain and development”ABS 1. CRITICAL CONDITION OF THE FETUS: RISK FACTORS AND PERINATAL OUTCOMES • E. Timokhina, A. Strizhakov, K. DerishABS 2. A MID-STUDY SAFETY CONTROL IN A HYPOTHERMIA PLUS MELATONIN CLINICAL TRIAL • A. Jerez-Calero, E. Fernandez-Marin, L. Serrano-López, AR. Gonzalez-Ramirez, J. Uberos-Fernandez, E. Narbona-LópezABS 3. EARLY PREDICTORS OF NEURODEVELOPMENTAL OUTCOME IN ASPHYXIATED INFANTS TREATED WITH SELECTIVE HEAD COOLING • C.Y. Chen, P.N. Tsao, H.C. Chou, W.S. HsiehABS 4. PRENATAL SURGERY OF MYELOMENINGOCELE: IS IT WORTH DOING? • H. Villalon, M. Pinto, S. Hosiasson, F. Rybertt, A. Fernandez, D. Tuma, L. Pizarro, C. SilvaABS 5. NEONATAL CEREBRAL SINOVENOUS THROMBOSIS: TWO CASES, TWO DIFFERENT GENE POLYMORPHISMS AND RISK FACTORS • O. Turan, D. Anuk Ince, L. Olcay, T. Sezer, K. Gulleroglu, Z.Y. Çelik, A. EcevitABS 6. DEVELOPMENT OF PREMATURE BORN CHILDREN – WHAT ABOUT LANGUAGE, READING AND WRITING? THE SPEECH AND LANGUAGE PATHOLOGIST’S VIEW • Z. Kolundžić, M. Lenček, A. Šimić Klarić, K. Pavičić DokozaABS 7. CHARACTERISTICS AND DISCHARGE OUTCOMES OF INFANTS UNDERGOING THERAPEUTIC HYPOTHERMIA IN AMERICAN NICUs • K. Ellsworth, M. Harris, M. Ellsworth, W. Carey, A. Spitzer, R. ClarkABS 8. PERINATAL STROKE: A LEADING CAUSE OF SEIZURES IN THE NEONATAL PERIOD. 4 YEAR EXPERIENCE IN A TERTIARY NEONATAL INTENSIVE CARE UNIT • P. Mikrou, S. Hands, E. Mawondo, S.V. Rasiah, M. BorooahABS 9. CARRIER SCREENING FOR FRAGILE X SYNDROME IN TAIWAN FROM 2013 TO 2015 • W.C. Yang, C.C. Hung, Y.N. Su, P.N. TsaoABS 10. LENTICULOSTRIATE VASCULOPATHY IN NEONATES: CASES SERIES REPORT • M.P. Priego-Ruiz, D. Trassierra-Molina, M.P. Jaraba-Caballero, M.D. Ordóñez-Díaz, I.M. Tofé-ValeraABS 11. CONGENITAL HYDROCEPHALUS SECONDARY TO ARACHNOID CYST: CASE REPORT • M.P. Priego-Ruiz, I.M. Tofé-Valera, N

  2. Specific in vivo binding in the rat brain of [{sup 18}F]RP 62203: A selective 5-HT{sub 2A} receptor radioligand for positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Besret, Laurent; Dauphin, Francois; Huard, Cecile; Lasne, Marie-Claire; Vivet, Richard; Mickala, Patrick; Barbelivien, Alexandra; Baron, Jean-Claude

    1996-02-01

    In vivo pharmacokinetic and brain binding characteristics of [{sup 18}F]RP 62203, a selective high-affinity serotonergic 5-HT{sub 2A} receptor antagonist, were assessed in the rat following intravenous injection of trace amount of the radioligand. The radioactive distribution profile observed in the brain 60 min after injection was characterized by greater than fourfold higher uptake in neocortex as compared to cerebellum (0.38 {+-} 0.07% injected dose/g, % ID/g and 0.08 {+-} 0.01 ID/g, respectively), consistent with in vivo specific binding to the 5-HT{sub 2A} receptor. Furthermore, specific [{sup 18}F]RP 62203 binding significantly correlated with the reported in vitro distribution of 5-HT{sub 2A} receptors, but not with known concentration profiles of dopaminergic D{sub 2} or adrenergic {alpha}{sub 1} receptors. Finally, detectable specific binding was abolished by pretreatment with large doses of ritanserin, a selective 5-HT{sub 2A} antagonist, which resulted in uniform uptakes across cortical, striatal and cerebellar tissues. Thus, [{sup 18}F]RP 62203 appears to be a promising selective tool to visualize and quantify 5-HT{sub 2A} brain receptors in vivo with positron emission tomography.

  3. Function of brain α2B-adrenergic receptor characterized with subtype-selective α2B antagonist and KO mice.

    Science.gov (United States)

    Luhrs, Lauren; Manlapaz, Cynthia; Kedzie, Karen; Rao, Sandhya; Cabrera-Ghayouri, Sara; Donello, John; Gil, Daniel

    2016-12-17

    Noradrenergic signaling, through the α 2A and α 2C adrenergic receptors modulates the cognitive and behavioral symptoms of disorders such as schizophrenia, attention deficit hyperactivity disorder (ADHD), and addiction. However, it is unknown whether the α 2B receptor has any significant role in CNS function. The present study elucidates the potential role of the α 2B receptor in CNS function via the discovery and use of the first subtype-selective α 2B antagonist (AGN-209419), and behavioral analyses of α-receptor knockout (KO) mice. Using AGN-209419 as radioligand, α 2B receptor binding sites were identified within the olfactory bulb, cortex, thalamus, cerebellum, and striatum. Based on the observed expression patterns of α 2 subtypes in the brain, we compared α 2B KO, α 2A KO and α 2C KO mice behavioral phenotypes with their respective wild-type lines in anxiety (plus maze), compulsive (marble burying), and sensorimotor (prepulse inhibition) tasks. α 2B KO mice exhibited increased marble burying and α 2C KO mice exhibited an increased startle response to a pulse stimulus, but otherwise intact prepulse inhibition. To further explore compulsive behavior, we evaluated novelty-induced locomotor hyperactivity and found that α 2B KO and α 2C KO mice exhibited increased locomotion in the open field. Interestingly, when challenged with amphetamine, α 2C KO mice increased activity at lower doses relative to either α 2A KO or WT mice. However, α 2B KO mice exhibited stereotypy at doses of amphetamine that were only locomotor stimulatory to all other genotypes. Following co-administration of AGN-209419 with low-dose amphetamine in WT mice, stereotypy was observed, mimicking the α 2B KO phenotype. These findings suggest that the α 2B receptor is involved in CNS behaviors associated with sensorimotor gating and compulsivity, and may be therapeutically relevant for disorders such as schizophrenia, ADHD, post-traumatic stress disorder, addiction, and

  4. Selected Abstracts of the 1st Congress of joint European Neonatal Societies (jENS 2015; Budapest (Hungary; September 16-20, 2015; Session “Brain & Development”

    Directory of Open Access Journals (Sweden)

    Various Authors

    2015-09-01

    Full Text Available Selected Abstracts of the 1st Congress of joint European Neonatal Societies (jENS 2015; Budapest (Hungary; September 16-20, 2015ORGANIZING INSTITUTIONSEuropean Society for Neonatology (ESN, European Society for Paediatric Research (ESPR, Union of European Neonatal & Perinatal Societies (UENPS, European Foundation for the Care of Newborn Infants (EFCNI, with the local host of Hungarian Society of Perinatology and Obstetric Anesthesiology, Hungarian Society of Perinatology (MPT, supported by Council of International Neonatal Nurses (COINN, organizing secretariat MCA Scientific EventsPROGRAMME COMMITTEEArtúr Beke (Hungarian Society, Morten Breindahl (ESN, Giuseppe Buonocore (UENPS, Pierre Gressens (ESPR, Silke Mader (EFCNI, Manuel Sánchez Luna (UENPS, Miklós Szabó (Hungarian Society of Perinatology, Luc Zimmermann (ESPR Session “Brain & Development”ABS 1. SEPARATE EFFECTS OF LOW PATERNAL AND MATERNAL EDUCATIONAL LEVEL ON RISK OF DEVELOPMENTAL DELAY IN 4-YEAR-OLD BOYS AND GIRLS • S. de Jong, M.R. Potijk, A.E. den Heijer, S.A. Reijneveld, A.F. Bos, J.M. KerstjensABS 2. THE ASSOCIATION BETWEEN PATERNAL EDUCATIONAL LEVEL AND DEVELOPMENTAL DELAY IN PRETERM AND TERM-BORN CHILDREN AT AGE 4 • S. de Jong, J.M. Kerstjens, A.E. den Heijer, A.F. Bos, S.A. Reijneveld, M.R. PotijkABS 3. NEUROPROTECTION BY NEURONAL OVEREXPRESSION OF THE SMALL GTPase-Ras IN HYPEROXIA-INDUCED NEONATAL BRAIN INJURY • M. Serdar, K. Kempe, J. Herz, R. Herrmann, B.S. Reinboth, R. Heumann, A. Ehrkamp, U. Felderhoff-Mueser, I. BendixABS 4. REFERENCE RANGES FOR CEREBRAL TISSUE OXYGEN INDEX (cTOI IN NEONATES DURING IMMEDIATE NEONATAL TRANSITION AFTER BIRTH • N. Baik, B. Urlesberger, B. Schwaberger, G. Schmölzer, A. Avian, L. Mileder, G. PichlerABS 4. REFERENCE RANGES FOR CEREBRAL TISSUE OXYGEN INDEX (cTOI IN NEONATES DURING IMMEDIATE NEONATAL TRANSITION AFTER BIRTH • N. Baik, B. Urlesberger, B. Schwaberger, G. Schmölzer, A. Avian, L. Mileder, G. PichlerABS 6. N

  5. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  6. Brain metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

    Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....

  7. Selective cognitive deficits and reduced hippocampal brain-derived neurotrophic factor mRNA expression in small-conductance calcium-activated K+ channel deficient mice

    DEFF Research Database (Denmark)

    Jacobsen, J P R; Redrobe, J P; Hansen, H H

    2009-01-01

    performed equally well in passive avoidance, object recognition and the Morris water maze. Thus, some aspects of working/short-term memory are disrupted in T/T mice. Using in situ hybridization, we further found the cognitive deficits in T/T mice to be paralleled by reduced brain-derived neurotrophic factor...... the brain following doxycycline treatment. We tested T/T and wild type (WT) littermate mice in five distinct learning and memory paradigms. In Y-maze spontaneous alternations and five-trial inhibitory avoidance the performance of T/T mice was markedly inferior to WT mice. In contrast, T/T and WT mice...

  8. Brain surgery

    Science.gov (United States)

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... cut depends on where the problem in the brain is located. The surgeon creates a hole in ...

  9. Brain Malformations

    Science.gov (United States)

    Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...

  10. [The selective participation of brain-specific non-histone proteins of chromatin Np-3,5 during the reproduction of a defensive habit to food in edible snails].

    Science.gov (United States)

    Kozyrev, S A; Nikitin, V P; Sherstnev, V V

    1991-01-01

    The role of brain-specific nonhistone proteins of chromatine Np-3.5 in the processes of reproduction of elaborated defensive habit to food was studied in previously learning snails. It was found, that gamma-globulines to Np-3.5 during tens of minutes inhibited behavioural and neuronal reactions elicited by a definite conditioned stimulus--carrot juice, without changing reactions to other conditioned stimulus--apple juice. gamma-globulines to other nonhistone proteins of chromatine did not influence the reproduction of food rejection habits. It was supposed that brain-specific nonhistone proteins of chromatine Np-3.5 were selectively involved in the molecular processes providing for neurophysiological mechanisms of information extraction from the long-term memory.

  11. N-acetylaspartate (NAA) levels in selected areas of the brain in patients with chronic schizophrenia treated with typical and atypical neuroleptics: a proton magnetic resonance spectroscopy (1H MRS) study.

    Science.gov (United States)

    Szulc, Agata; Galińska, Beata; Tarasów, Eugeniusz; Kubas, Bozena; Dzienis, Wojciech; Konarzewska, Beata; Poplawska, Regina; Tomczak, Anna A; Czernikiewicz, Andrzej; Walecki, Jerzy

    2007-05-01

    NAA, marker of neurons integrity and viability, is one of the most important brain metabolites visible in 1H MRS. In most studies of schizophrenia, the decrease of NAA level was observed in the temporal, frontal lobes and in the thalamus. This finding was observed more often among chronic patients, what suggests the influence of disease duration or the effect of neuroleptic treatment. The aim of the present study was the comparison of NAA levels in brain of schizophrenic patients taking typical and atypical neuroleptics. We analyzed the NAA levels in selected brain areas in 58 schizophrenic patients and 21 healthy controls. 10 patients were treated with typical neuroleptics, 10 patients with clozapine, 17 received olanzapine and 21 - risperidone. 1H MRS was performed on a 1,5 MR scanner with PRESS sequence. Voxels of 2x2x2 cm were localized in the left frontal, left temporal lobe and left thalamus. There were no differences in NAA levels between patients on typical and atypical medications analyzed together and separately (olanzapine, clozapine and risperidone groups). We also did not find any differences between patients taking selected atypical neuroleptics and controls. The NAA level in the thalamus in the group of patients receiving typical antipsychotics was the lowest among all groups and differed significantly from healthy controls. The results of our study suggest that atypical neuroleptics may have favorable effect on NAA concentration in brain of schizophrenic patients. Decrease in NAA level in patients taking typical medication may be caused by the progression of the disease or by the direct action of these drugs.

  12. A combined MRI and MRSI based multiclass system for brain tumour recognition using LS-SVMs with class probabilities and feature selection.

    NARCIS (Netherlands)

    Luts, J.; Heerschap, A.; Suykens, J.A.; Huffel, S. van

    2007-01-01

    OBJECTIVE: This study investigates the use of automated pattern recognition methods on magnetic resonance data with the ultimate goal to assist clinicians in the diagnosis of brain tumours. Recently, the combined use of magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging

  13. Fetal brain 11β-hydroxysteroid dehydrogenase type 2 selectively determines programming of adult depressive-like behaviors and cognitive function, but not anxiety behaviors in male mice.

    Science.gov (United States)

    Wyrwoll, Caitlin; Keith, Marianne; Noble, June; Stevenson, Paula L; Bombail, Vincent; Crombie, Sandra; Evans, Louise C; Bailey, Matthew A; Wood, Emma; Seckl, Jonathan R; Holmes, Megan C

    2015-09-01

    Stress or elevated glucocorticoids during sensitive windows of fetal development increase the risk of neuropsychiatric disorders in adult rodents and humans, a phenomenon known as glucocorticoid programming. 11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2), which catalyses rapid inactivation of glucocorticoids in the placenta, controls access of maternal glucocorticoids to the fetal compartment, placing it in a key position to modulate glucocorticoid programming of behavior. However, the importance of the high expression of 11β-HSD2 within the midgestational fetal brain is unknown. To examine this, a brain-specific knockout of 11β-HSD2 (HSD2BKO) was generated and compared to wild-type littermates. HSD2BKO have markedly diminished fetal brain 11β-HSD2, but intact fetal body and placental 11β-HSD2 and normal fetal and placental growth. Despite normal fetal plasma corticosterone, HSD2BKO exhibit elevated fetal brain corticosterone levels at midgestation. As adults, HSD2BKO show depressive-like behavior and have cognitive impairments. However, unlike complete feto-placental deficiency, HSD2BKO show no anxiety-like behavioral deficits. The clear mechanistic separation of the programmed components of depression and cognition from anxiety implies distinct mechanisms of pathogenesis, affording potential opportunities for stratified interventions. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  14. Discrete mapping of brain Mu and delta opioid receptors using selective peptides: Quantitative autoradiography, species differences and comparison with kappa receptors

    Energy Technology Data Exchange (ETDEWEB)

    Sharif, N.A.; Hughes, J. (Addenbrookes Hospital Site, Cambridge (England))

    1989-05-01

    The opioid peptides, (3H)DAGO and (3H)DPDPE, bound to rat and guinea pig brain homogenates with a high, nanomolar affinity and to a high density of mu and delta receptors, respectively. (3H)DAGO binding to mu receptors was competitively inhibited by unlabelled opioids with the following rank order of potency: DAGO greater than morphine greater than DADLE greater than naloxone greater than etorphine much greater than U50488 much greater than DPDPE. In contrast, (3H)DPDPE binding to delta receptors was inhibited by compounds with the following rank order of potency: DPDPE greater than DADLE greater than etorphine greater than dynorphin(1-8) greater than naloxone much greater than U50488 much greater than DAGO. These profiles were consistent with specific labelling of the mu and delta opioid receptors, respectively. In vitro autoradiographic techniques coupled with computer-assisted image analyses revealed a discrete but differential anatomical localization of mu and delta receptors in the rat and guinea pig brain. In general, mu and delta receptor density in the rat exceeded that in the guinea pig brain and differed markedly from that of kappa receptors in these species. However, while mu receptors were distributed throughout the brain with hotspots in the fore-, mid- and hindbrain of the two rodents, the delta sites were relatively diffusely distributed, and were mainly concentrated in the forebrain with particularly high levels within the olfactory bulb (OB), n. accumbens and striatum. Notable regions of high density of mu receptors in the rat and guinea pig brain were the accessory olfactory bulb, striatal patches and streaks, amygdaloid nuclei, ventral hippocampal subiculum and dentate gyrus, numerous thalamic nuclei, geniculate bodies, central grey, superior and inferior colliculi, solitary and pontine nuclei and s. nigra.

  15. Circadian expression of steroidogenic cytochromes P450 in the mouse adrenal gland--involvement of cAMP-responsive element modulator in epigenetic regulation of Cyp17a1.

    Science.gov (United States)

    Košir, Rok; Zmrzljak, Ursula Prosenc; Bele, Tanja; Acimovic, Jure; Perse, Martina; Majdic, Gregor; Prehn, Cornelia; Adamski, Jerzy; Rozman, Damjana

    2012-05-01

    The cytochrome P450 (CYP) genes Cyp51, Cyp11a1, Cyp17a1, Cyb11b1, Cyp11b2 and Cyp21a1 are involved in the adrenal production of corticosteroids, whose circulating levels are circadian. cAMP signaling plays an important role in adrenal steroidogenesis. By using cAMP responsive element modulator (Crem) knockout mice, we show that CREM isoforms contribute to circadian expression of steroidogenic CYPs in the mouse adrenal gland. Most striking was the CREM-dependent hypomethylation of the Cyp17a1 promoter at zeitgeber time 12, which resulted in higher Cyp17a1 mRNA and protein expression in the knockout adrenal glands. The data indicate that products of the Crem gene control the epigenetic repression of Cyp17 in mouse adrenal glands. © 2011 The Authors Journal compilation © 2011 FEBS.

  16. Measurement of creatine kinase reaction rate in human brain using magnetization transfer image-selected in vivo spectroscopy (MT-ISIS) and a volume ³¹P/¹H radiofrequency coil in a clinical 3-T MRI system.

    Science.gov (United States)

    Jeong, Eun-Kee; Sung, Young-Hoon; Kim, Seong-Eun; Zuo, Chun; Shi, Xianfeng; Mellon, Eric A; Renshaw, Perry F

    2011-08-01

    High-energy phosphate metabolism, which allows the synthesis and regeneration of adenosine triphosphate (ATP), is a vital process for neuronal survival and activity. In particular, creatine kinase (CK) serves as an energy reservoir for the rapid buffering of ATP levels. Altered CK enzyme activity, reflecting compromised high-energy phosphate metabolism or mitochondrial dysfunction in the brain, can be assessed using magnetization transfer (MT) MRS. MT (31)P MRS has been used to measure the forward CK reaction rate in animal and human brain, employing a surface radiofrequency coil. However, long acquisition times and excessive radiofrequency irradiation prevent these methods from being used routinely for clinical evaluations. In this article, a new MT (31)P MRS method is presented, which can be practically used to measure the CK forward reaction rate constant in a clinical MRI system employing a volume head (31)P coil for spatial localization, without contamination from the scalp muscle, and an acquisition time of 30 min. Other advantages associated with the method include radiofrequency homogeneity within the regions of interest of the brain using a volume coil with image-selected in vivo spectroscopy localization, and reduction of the specific absorption rate using nonadiabatic radiofrequency pulses for MT saturation. The mean value of k(f) was measured as 0.320 ± 0.075 s(-1) from 10 healthy volunteers with an age range of 18-40 years. These values are consistent with those obtained using earlier methods, and the technique may be used routinely to evaluate energetic processes in the brain on a clinical MRI system. Copyright © 2010 John Wiley & Sons, Ltd.

  17. Caffeine exposure during rat brain development causes memory impairment in a sex selective manner that is offset by caffeine consumption throughout life.

    Science.gov (United States)

    Ardais, Ana Paula; Rocha, Andréia S; Borges, Maurício Felisberto; Fioreze, Gabriela T; Sallaberry, Cássia; Mioranzza, Sabrina; Nunes, Fernanda; Pagnussat, Natália; Botton, Paulo Henrique S; Cunha, Rodrigo A; Porciúncula, Lisiane de Oliveira

    2016-04-15

    Caffeine is the psychostimulant most consumed worldwide. In moderate doses, it affords a beneficial effect in adults and upon aging, but has a deleterious effect during brain development. We now tested if caffeine consumption by rats (0.1, 0.3, 1.0 g/L in the drinking water, only during active cycle and weekdays) during adulthood could revert the potentially negative effects of caffeine during early life. Thus, we compared caffeine intake starting 15 days before mating and lasting either up to weaning (development) or up to adulthood, on behavior and synaptic proteins in male and female rats. Recognition memory was impaired only in female rats receiving caffeine (0.3 and 1.0 g/L) during development, coincident with increased proBDNF and unchanged BDNF levels in the hippocampus. Caffeine in both treatment regimens caused hyperlocomotion only in male rats, whereas anxiety-related behavior was attenuated in both sexes by caffeine (1.0 g/L) throughout life. Both caffeine treatment regimens decreased GFAP (as an astrocyte marker) and SNAP-25 (as a nerve terminals marker) in the hippocampus from male rats. TrkB receptor was decreased in the hippocampus from both sexes and treatment regimens. These findings revealed that caffeine intake during a specific time window of brain development promotes sex-dependent behavioral outcomes related to modification in BDNF signaling. Furthermore, caffeine throughout life can overcome the deleterious effects of caffeine on recognition memory during brain development in female rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Selection and validation of a set of reliable reference genes for quantitative RT-PCR studies in the brain of the Cephalopod Mollusc Octopus vulgaris

    Directory of Open Access Journals (Sweden)

    Biffali Elio

    2009-07-01

    Full Text Available Abstract Background Quantitative real-time polymerase chain reaction (RT-qPCR is valuable for studying the molecular events underlying physiological and behavioral phenomena. Normalization of real-time PCR data is critical for a reliable mRNA quantification. Here we identify reference genes to be utilized in RT-qPCR experiments to normalize and monitor the expression of target genes in the brain of the cephalopod mollusc Octopus vulgaris, an invertebrate. Such an approach is novel for this taxon and of advantage in future experiments given the complexity of the behavioral repertoire of this species when compared with its relatively simple neural organization. Results We chose 16S, and 18S rRNA, actB, EEF1A, tubA and ubi as candidate reference genes (housekeeping genes, HKG. The expression of 16S and 18S was highly variable and did not meet the requirements of candidate HKG. The expression of the other genes was almost stable and uniform among samples. We analyzed the expression of HKG into two different set of animals using tissues taken from the central nervous system (brain parts and mantle (here considered as control tissue by BestKeeper, geNorm and NormFinder. We found that HKG expressions differed considerably with respect to brain area and octopus samples in an HKG-specific manner. However, when the mantle is treated as control tissue and the entire central nervous system is considered, NormFinder revealed tubA and ubi as the most suitable HKG pair. These two genes were utilized to evaluate the relative expression of the genes FoxP, creb, dat and TH in O. vulgaris. Conclusion We analyzed the expression profiles of some genes here identified for O. vulgaris by applying RT-qPCR analysis for the first time in cephalopods. We validated candidate reference genes and found the expression of ubi and tubA to be the most appropriate to evaluate the expression of target genes in the brain of different octopuses. Our results also underline the

  19. Effect of sibutramine on 5-hydroxyindole acetic acid levels and selected oxidative biomarkers on brain regions of female rats in the presence of zinc.

    Science.gov (United States)

    Guzmán, David C; García, Ernestina H; Mejía, Gerardo B; Olguín, Hugo J; Jiménez, Francisca T; Soto, Erick B; Del Angel, Daniel S; Aparicio, Liliana C

    2012-05-01

    A number of drugs, like sibutramine, which are used clinically in weight control, act on serotonergic metabolism. However, their relation with zinc and free radical (FR) production in central nervous system remains unknown. This study aimed to evaluate the effect of sibutramine and zinc on FR production. Female Wistar rats (about 250 g) were used in this study. The animals received 400 μg/kg of zinc and 10 mg/kg of sibutramine intraperitoneally every 36 hr for 15 days. At the end of the study, the rats were killed and their brains used for the measurement of lipid peroxidation thiobarbituric acid-reactive substances (TBARS), reduced glutathione (GSH), hydrogen peroxide (H(2) O(2) ), calcium and 5-hydroxyindole acetic acid (5-HIAA) levels, all by means of validated methods. Corporal weight and food consumption were found to be decreased in the zinc/sibutramine group. TBARS decreased in cortex, hemispheres and medulla oblongata. GSH decreased in cortex, hemispheres and cerebellum in the sibutramine group. Zinc given alone and in combination with sibutramine decreased H(2) O(2) concentration in cortex, hemispheres and cerebellum but increased calcium and 5-HIAA concentration in all brain regions. Our results suggest that sibutramine and zinc are associated with weight loss, an effect that was more pronounced in the group treated with both drugs. Reduction in oxidative stress may be involved in these effects. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

  20. Brain Diseases

    Science.gov (United States)

    The brain is the control center of the body. It controls thoughts, memory, speech, and movement. It regulates the function of many organs. When the brain is healthy, it works quickly and automatically. However, ...

  1. Chernobyl birds have smaller brains.

    Directory of Open Access Journals (Sweden)

    Anders Pape Møller

    2011-02-01

    Full Text Available Animals living in areas contaminated by radioactive material from Chernobyl suffer from increased oxidative stress and low levels of antioxidants. Therefore, normal development of the nervous system is jeopardized as reflected by high frequencies of developmental errors, reduced brain size and impaired cognitive abilities in humans. Alternatively, associations between psychological effects and radiation have been attributed to post-traumatic stress in humans.Here we used an extensive sample of 550 birds belonging to 48 species to test the prediction that even in the absence of post-traumatic stress, there is a negative association between relative brain size and level of background radiation. We found a negative association between brain size as reflected by external head volume and level of background radiation, independent of structural body size and body mass. The observed reduction in brain size in relation to background radiation amounted to 5% across the range of almost a factor 5,000 in radiation level. Species differed significantly in reduction in brain size with increasing background radiation, and brain size was the only morphological character that showed a negative relationship with radiation. Brain size was significantly smaller in yearlings than in older individuals.Low dose radiation can have significant effects on normal brain development as reflected by brain size and therefore potentially cognitive ability. The fact that brain size was smaller in yearlings than in older individuals implies that there was significant directional selection on brain size with individuals with larger brains experiencing a viability advantage.

  2. Brain Aneurysm

    Science.gov (United States)

    A brain aneurysm is an abnormal bulge or "ballooning" in the wall of an artery in the brain. They are sometimes called berry aneurysms because they ... often the size of a small berry. Most brain aneurysms produce no symptoms until they become large, ...

  3. Brain Development

    Science.gov (United States)

    ... Become a Member Home Early Development & Well-Being Brain Development A child’s brain undergoes an amazing period of development from birth ... neural connections each second. The development of the brain is influenced by many factors, including a child’s ...

  4. Brain 'talks over' boring quotes: top-down activation of voice-selective areas while listening to monotonous direct speech quotations.

    Science.gov (United States)

    Yao, Bo; Belin, Pascal; Scheepers, Christoph

    2012-04-15

    In human communication, direct speech (e.g., Mary said, "I'm hungry") is perceived as more vivid than indirect speech (e.g., Mary said that she was hungry). This vividness distinction has previously been found to underlie silent reading of quotations: Using functional magnetic resonance imaging (fMRI), we found that direct speech elicited higher brain activity in the temporal voice areas (TVA) of the auditory cortex than indirect speech, consistent with an "inner voice" experience in reading direct speech. Here we show that listening to monotonously spoken direct versus indirect speech quotations also engenders differential TVA activity. This suggests that individuals engage in top-down simulations or imagery of enriched supra-segmental acoustic representations while listening to monotonous direct speech. The findings shed new light on the acoustic nature of the "inner voice" in understanding direct speech. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Left Brain. Right Brain. Whole Brain

    Science.gov (United States)

    Farmer, Lesley S. J.

    2004-01-01

    As the United States student population is becoming more diverse, library media specialists need to find ways to address these distinctive needs. However, some of these differences transcend culture, touching on variations in the brain itself. Most people have a dominant side of the brain, which can affect their personality and learning style.…

  6. Brain Basics: Know Your Brain

    Science.gov (United States)

    ... however, the brain is beginning to relinquish its secrets. Scientists have learned more about the brain in ... through the activity of these lobes. At the top of each temporal lobe is an area responsible ...

  7. Insulin and the brain.

    Science.gov (United States)

    Derakhshan, Fatemeh; Toth, Cory

    2013-03-01

    Mainly known for its role in peripheral glucose homeostasis, insulin has also significant impact within the brain, functioning as a key neuromodulator in behavioral, cellular, biochemical and molecular studies. The brain is now regarded as an insulin-sensitive organ with widespread, yet selective, expression of the insulin receptor in the olfactory bulb, hypothalamus, hippocampus, cerebellum, amygdala and cerebral cortex. Insulin receptor signaling in the brain is important for neuronal development, glucoregulation, feeding behavior, body weight, and cognitive processes such as with attention, executive functioning, learning and memory. Emerging evidence has demonstrated insulin receptor signaling to be impaired in several neurological disorders. Moreover, insulin receptor signaling is recognized as important for dendritic outgrowth, neuronal survival, circuit development, synaptic plasticity and postsynaptic neurotransmitter receptor trafficking. We review the multiple roles of insulin in the brain, as well as its endogenous trafficking to the brain or its exogenous intervention. Although insulin can be directly targeted to the brain via intracerebroventricular (ICV) or intraparenchymal delivery, these invasive techniques are with significant risk, necessitating repeated surgical intervention and providing potential for systemic hypoglycemia. Another method, intranasal delivery, is a non-invasive, safe, and alternative approach which rapidly targets delivery of molecules to the brain while minimizing systemic exposure. Over the last decades, the delivery of intranasal insulin in animal models and human patients has evolved and expanded, permitting new hope for associated neurodegenerative and neurovascular disorders.

  8. Selection for low mortality in laying hens affects catecholamine levels in the arcopallium, a brain area involved in fear and motor regulation

    NARCIS (Netherlands)

    Kops, M.S.; Haas, de E.N.; Rodenburg, T.B.; Ellen, E.D.; Korte-Bouws, G.A.H.; Olivier, B.; Güntürkün, O.; Korte, S.M.; Bolhuis, J.E.

    2013-01-01

    Feather pecking (FP) in laying hens may cause mortality due to cannibalism. Novel breeding methods using survival days of group-housed siblings allow for the genetic selection of laying hens with low mortality (LML: low mortality line) due to cannibalism. Previous studies have demonstrated less

  9. Selective attention to spatial and non-spatial visual stimuli is affected differentially by age: Effects on event-related brain potentials and performance data

    NARCIS (Netherlands)

    Talsma, D.; Kok, Albert; Ridderinkhof, K. Richard

    2006-01-01

    To assess selective attention processes in young and old adults, behavioral and event-related potential (ERP) measures were recorded. Streams of visual stimuli were presented from left or right locations (Experiment 1) or from a central location and comprising two different spatial frequencies

  10. Inhibition of Pain and Pain-Related Brain Activity by Heterotopic Noxious Counter-Stimulation and Selective Attention in Chronic Non-Specific Low Back Pain.

    Science.gov (United States)

    Ladouceur, Alexandra; Rustamov, Nabi; Dubois, Jean-Daniel; Tessier, Jessica; Lehmann, Alexandre; Descarreaux, Martin; Rainville, Pierre; Piché, Mathieu

    2017-10-10

    The aim of the present study was to assess inhibition of pain and somatosensory-evoked potentials (SEPs) by heterotopic noxious counter-stimulation (HNCS) and by selective attention in patients with chronic non-specific LBP. Seventeen patients and age/sex-matched controls were recruited (10 men, 7 women; mean age ± SD: 43.3 ± 10.4 and 42.7 ± 11.1, respectively). On average, patients with LBP reported pain duration of 7.6 ± 6.5 years, light to moderate disability (19.3 ± 5.7/100) and low clinical pain intensity (21.8 ± 1.5/100), while pain catastrophizing, state and trait anxiety and depressive symptoms were not significantly different between groups (all p's >0.05). HNCS and selective attention had differential inhibitory effects on pain and SEP, but no difference was observed between groups. Across both groups, HNCS decreased pain (p = 0.06) as well as the N100 and the N150 components of SEP (p's selective attention only decreased pain (p attention was directed toward the HNCS stimulus (pselective attention. Importantly, this experiment was carefully designed to control for non-specific effects associated with the repetition of the test stimulus and the effect of an innocuous counter-stimulation. It remains to be determined if these results hold for patients with severe LBP and psychological symptoms or whether symptom severity may be associated with pain inhibition deficits. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Coupled Imaging with [18F]FBB and [18F]FDG in AD Subjects Show a Selective Association Between Amyloid Burden and Cortical Dysfunction in the Brain.

    Science.gov (United States)

    Chiaravalloti, Agostino; Castellano, Anna Elisa; Ricci, Maria; Barbagallo, Gaetano; Sannino, Pasqualina; Ursini, Francesco; Karalis, Georgios; Schillaci, Orazio

    2018-02-05

    The present study was aimed to investigate the relationships between dysfunction of cortical glucose metabolism as detectable by means of 2-deoxy-2-[ 18 F]fluoro -D-glucose ([ 18 F]FDG) positron emission tomography/x-ray computed tomography (PET/CT) and amyloid burden as detectable by means of 4-{(E)-2-[4-(2-{2-[2-[ 18 F]fluoroethoxy]ethoxy}ethoxy)phenyl]vinyl}-N-methylaniline (florbetaben; [ 18 F]FBB) in a group of patients affected by Alzheimer's disease (AD). We examined 38 patients newly diagnosed with AD according to the NINCDS-ADRDA criteria. All the subjects underwent a PET/CT scan using both [ 18 F]FDG and [ 18 F]FBB with an average interval of 1 month. We used statistical parametric mapping (SPM8) implemented in Matlab R2012b and WFU pickatlas for the definition of a region of interest (ROI) mask including the whole cortex. These data were then normalized on the counts of the cerebellum and then used for a regression analysis on [ 18 F]FDG scans in SPM. Furthermore, 58 control subjects were used as control group for [ 18 F]FDG PET/CT scans. SPM analysis in AD patients showed a significant negative correlation between [ 18 F] FBB and [ 18 F] FDG uptake in temporal and parietal lobes bilaterally. Of note, these areas in AD patients displayed a marked glucose hypometabolism compared to control group. Combined imaging with [ 18 F]FBB and [ 18 FFDG shows that amyloid burden in the brain is related to cortical dysfunction of temporal and parietal lobes in AD.

  12. Brain glycogen

    DEFF Research Database (Denmark)

    Obel, Linea Lykke Frimodt; Müller, Margit S; Walls, Anne B

    2012-01-01

    Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g., liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia....... In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies-it is a highly dynamic molecule with versatile implications in brain function, i.e., synaptic...... activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms...

  13. Variation in anticonvulsant selection and EEG monitoring following severe traumatic brain injury in children – Understanding resource availability in sites participating in a comparative effectiveness study

    Science.gov (United States)

    Kurz, Jonathan E.; Poloyac, Samuel M.; Abend, Nicholas S.; Fabio, Anthony; Bell, Michael J.; Wainwright, Mark S.

    2016-01-01

    Objective Early post-traumatic seizures (PTS) may contribute to worsened outcomes after traumatic brain injury (TBI). Evidence to guide the evaluation and management of early PTS in children is limited. We undertook a survey of current practices of continuous electroencephalographic monitoring (cEEG), seizure prophylaxis and the management of early PTS to provide essential information for trial design and the development of PTS management pathways. Design Surveys were sent to site principal investigators at all 43 sites participating in the ADAPT (Approaches and Decisions in Acute Pediatric TBI) trial at the time of the survey. Surveys consisted of 12 questions addressing strategies to (i) implement cEEG monitoring, (ii) PTS prophylaxis, (iii) treat acute PTS, (iv) treat status epilepticus (SE) and refractory status epilepticus (RSE) and (v) monitor anti-seizure drug levels. Setting Institutions comprised a mixture of free-standing children’s hospitals and university medical centers across the United States and Europe. Measurements and Main Results cEEG monitoring was available in the pediatric intensive care unit in the overwhelming majority of clinical sites (98%); however, the plans to operationalize such monitoring for children varied considerably. A similar majority of sites report that administration of prophylactic anti-seizure medications is anticipated in children (93%), yet a minority reports that a specified protocol for treatment of PTS is in place (43%). Reported medication choices varied substantially between sites, but the majority of sites reported pentobarbital for RSE (81%). Presence of an treatment protocols for seizure prophylaxis, early PTS, post-traumatic SE and RSE was associated with decreased reported medications (all p pediatric severe TBI. The substantial variation in cEEG implementation, choice of seizure prophylaxis medications, and management of early PTS across institutions was reported, signifying areas of clinical uncertainty that

  14. Brain-computer interface

    DEFF Research Database (Denmark)

    2014-01-01

    A computer-implemented method of providing an interface between a user and a processing unit, the method comprising : presenting one or more stimuli to a user, each stimulus varying at a respective stimulation frequency, each stimulation frequency being associated with a respective user......-selectable input; receiving at least one signal indicative of brain activity of the user; and determining, from the received signal, which of the one or more stimuli the user attends to and selecting the user-selectable input associated with the stimulation frequency of the determined stimuli as being a user...

  15. Specific dose-dependent effects of ethane 1,2-dimethanesulfonate in rat and mouse Leydig cells and non-steroidogenic cells on programmed cell death

    NARCIS (Netherlands)

    F.F.G. Rommerts (Focko); L. Kuhne; W.A. van Cappellen (Gert); D.M. Stocco; S.R. King (Steven); A. Jankowska

    2004-01-01

    textabstractThe mechanism by which ethane 1,2-dimethanesulfonate (EDS) selectively kills Leydig cells is poorly understood. To characterize further the cell-specific actions of EDS, we studied biochemical and morphological changes during apoptosis in different Leydig cell and

  16. Brain imaging

    International Nuclear Information System (INIS)

    Mishkin, F.S.

    1978-01-01

    The techniques of brain imaging and results in perfusion studies and delayed images are outlined. An analysis of the advantages and disadvantages of the brain scan in a variety of common problems is discussed, especially as compared with other available procedures. Both nonneoplastic and neoplastic lesions are considered. (Auth/C.F.)

  17. Effects of the brain-penetrant and selective 5-HT6 receptor antagonist SB-399885 in animal models of anxiety and depression.

    Science.gov (United States)

    Wesołowska, Anna; Nikiforuk, Agnieszka

    2007-04-01

    The effects of a selective 5-HT(6) receptor antagonist, SB-399885 (N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide), were evaluated in behavioural tests sensitive to clinically effective anxiolytic- and antidepressant-compounds using diazepam and imipramine as reference drugs. In the Vogel conflict drinking test in rats, SB-399885 (1-3mg/kg i.p.) caused an anxiolytic-like activity comparable to that of diazepam (2.5-5mg/kg i.p.). An anxiolytic-like effect was also seen in the elevated plus-maze test in rats, where SB-399885 (0.3-3mg/kg i.p.) was slightly weaker than diazepam (2.5-5mg/kg i.p.). In the four-plate test in mice, SB-399885 (3-20mg/kg i.p.) showed an anxiolytic-like effect which was weaker than that produced by diazepam (2.5-5mg/kg i.p.). In the forced swim test in rats, SB-399885 (10mg/kg i.p.) significantly shortened the immobility time and the effect was stronger than that of imipramine (30mg/kg i.p.). In the forced swim test in mice, SB-399885 (20-30mg/kg i.p.) had an anti-immobility action, comparable to imipramine (30mg/kg i.p.) and also in the tail suspension test in mice, SB-399885 (10-30mg/kg i.p.) had an antidepressant-like effect, though was weaker than imipramine (10-20mg/kg i.p.). The tested 5-HT(6) antagonist (3-20mg/kg i.p.) shortened the walking time of rats in the open field test and, at a dose of 30mg/kg i.p. reduced the locomotor activity of mice. SB-399885 (in doses up to 30mg/kg i.p.) did not affect motor coordination in mice and rats tested in the rota-rod test. Such data indicate that the selective 5-HT(6) receptor antagonist SB-399885had specific effects, indicative of this compound's anxiolytic and antidepressant potential.

  18. [The Influence of the Functional State of Brain Regulatory Structures on the Programming, Selective Regulation and Control of Cognitive Activity in Children. Report I: Neuropsychological and EEG Analysis of Age-Related Changes in Brain Regulatory Functions in Children Aged 9-12 Years].

    Science.gov (United States)

    Semenova, A; Machinskaya, R I; Lomakin, D I

    2015-01-01

    Age-related changes in brain regulatory functions in children aged from 9 to 12 years with typical development were studied by means of neuropsychological and EEG analysis. The participants of the study were 107 children without learning difficulties and behavior deviations; they were devided into three groups (9-10, 10-11 and 11-12 years). The neuropsychological tests revealed nonlinear age-related changes in different executive brain functions. The group of 10-11-year-old children showed better results in programming, in- hibition of impulsive reactions and in the perception of socially relevant information than the group of 9-10- year-old children. At the same time, these children had more difficulties with selective activity regulation as compared with the younger group. The difficulties were mainly caused by switching from one element of the program to another and by retention of learned sequence of actions. These children also showed a lower level of motivation for task performance. The children aged 11-12 years had less difficulties with selective activity regulation; however, impulsive behavior was more frequent; these children also had a higher level of task performance motivation than in children aged 10-11 years. The analysis of resting state EEG revealed age-related differences in deviated EEG patterns associated with non-optimal functioning of fronto-thalamic system and hypothalamic structures. The incidence of these two types of EEG patterns was significantly higher in children aged 10-11 years as compared with children aged 9-10 years. The EEG of the groups of 10-11 and 11-12-years-old children did not show any significant differences.

  19. Central nervous system: brain

    International Nuclear Information System (INIS)

    Mishkin, F.S.

    1975-01-01

    Present radiopharmaceuticals and detector systems have provided nuclear medicine physicians with tools capable of detecting a variety of brain abnormalities with little radiation exposure to pediatric patients. It is essential that the referring physician as well as the physician performing the procedure recognize both the limitations and virtues of these techniques. Appropriate selection of brain imaging procedures in each specific case must be the rule. Brain scintigraphy reliably solves certain problems, such as detecting or excluding intracranial tumors and identifying early cerebral inflammatory disease, cerebral ischemic disease, and a variety of congenital anomalies. Other situations, such as seizures without a focal neurologic deficit, acute meningitis, and hydrocephalus, are less often benefited by these studies. The role of these procedures in acute trauma and its sequelae is at the present time limited in pediatric practice. (auth)

  20. Brain edema associated with unruptured brain arteriovenous malformations

    International Nuclear Information System (INIS)

    Kim, Bum-soo; Sarma, Dipanka; Lee, Seon-Kyu; ter Brugge, Karel G.

    2009-01-01

    Brain edema in unruptured brain arteriovenous malformations (AVMs) is rare; this study examines (1) its frequency and clinical presentation, (2) imaging findings with emphasis on venous drainage abnormalities, and (3) implications of these findings on natural history and management. Presentation and imaging features of all unruptured brain AVMs were prospectively collected in our brain AVM database. Neurological findings, size, location, venous drainage pattern, presence of venous thrombosis, ectasia, or stenosis, and brain edema were specifically recorded. Treatment details of all patients with brain edema and their clinical and imaging follow-up were reviewed. Finally, a comparison was made between patients with and without edema. Brain edema was found in 13/329 unruptured brain AVMs (3.9%). Neurological deficit (46.2%), venous thrombosis (38.5%), venous ectasia (84.6%), stenosis (38.5%), and contrast stagnation in the draining veins (84.6%) were more frequent in patients with brain edema than without edema. Eight patients with brain edema received specific treatment (embolization = 5, surgery = 2, radiosurgery = 1). Clinical features correlated well with change in degree of edema in six. Three of five embolized patients were stable or showed improvement after the procedure. On follow-up, however, intracranial hemorrhage developed in three. Brain edema in unruptured brain AVMs is rare, 3.9% in this series. Venous outflow abnormalities are frequently associated and appear to contribute to the development of edema. Progressive nonhemorrhagic symptoms are also associated, with a possible increased risk of hemorrhage. Palliative embolization arrests the nonhemorrhagic symptoms in selected patients, although it may not have an effect on hemorrhagic risk. (orig.)

  1. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  2. Brain Stimulation Therapies

    Science.gov (United States)

    ... Magnetic Seizure Therapy Deep Brain Stimulation Additional Resources Brain Stimulation Therapies Overview Brain stimulation therapies can play ... for a shorter recovery time than ECT Deep Brain Stimulation Deep brain stimulation (DBS) was first developed ...

  3. Brain radiation - discharge

    Science.gov (United States)

    Radiation - brain - discharge; Cancer - brain radiation; Lymphoma - brain radiation; Leukemia - brain radiation ... Decadron) while you are getting radiation to the brain. It may make you hungrier, cause leg swelling ...

  4. Cyclic adenosine 3',5'-monophosphate (cAMP) enhances cAMP-responsive element binding (CREB) protein phosphorylation and phospho-CREB interaction with the mouse steroidogenic acute regulatory protein gene promoter.

    Science.gov (United States)

    Clem, Brian F; Hudson, Elizabeth A; Clark, Barbara J

    2005-03-01

    Steroidogenic acute regulatory protein (StAR) transcription is regulated through cAMP-protein kinase A-dependent mechanisms that involve multiple transcription factors including the cAMP-responsive element binding protein (CREB) family members. Classically, binding of phosphorylated CREB to cis-acting cAMP-responsive elements (5'-TGACGTCA-3') within target gene promoters leads to recruitment of the coactivator CREB binding protein (CBP). Herein we examined the extent of CREB family member phosphorylation on protein-DNA interactions and CBP recruitment with the StAR promoter. Immunoblot analysis revealed that CREB, cAMP-responsive element modulator (CREM), and activating transcription factor (ATF)-1 are expressed in MA-10 mouse Leydig tumor cells, yet only CREB and ATF-1 are phosphorylated. (Bu)2cAMP treatment of MA-10 cells increased CREB phosphorylation approximately 2.3-fold within 30 min but did not change total nuclear CREB expression levels. Using DNA-affinity chromatography, we now show that CREB and ATF-1, but not CREM, interact with the StAR promoter, and this interaction is dependent on the activator protein-1 (AP-1) cis-acting element within the cAMP-responsive region. In addition, (Bu)2cAMP-treatment increased phosphorylated CREB (P-CREB) association with the StAR promoter but did not influence total CREB interaction. In vivo chromatin immunoprecipitation assays demonstrated CREB binding to the StAR proximal promoter is independent of (Bu)2cAMP-treatment, confirming our in vitro analysis. However, (Bu)2cAMP-treatment increased P-CREB and CBP interaction with the StAR promoter, demonstrating for the first time the physical role of P-CREB:DNA interactions in CBP recruitment to the StAR proximal promoter.

  5. Brain abscess

    Science.gov (United States)

    ... found. However, the most common source is a lung infection. Less often, a heart infection is the cause. The following raise your chance of developing a brain abscess: A weakened immune system (such as in people ...

  6. Gut Microbiota-brain Axis

    Institute of Scientific and Technical Information of China (English)

    Hong-Xing Wang; Yu-Ping Wang

    2016-01-01

    Objective:To systematically review the updated information about the gut microbiota-brain axis.Data Sources:All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of"gut microbiota","gut-brain axis",and "neuroscience".Study Selection:All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results:It is well-recognized that gut microbiota affects the brain's physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain's neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions:Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.

  7. Brain imaging and brain function

    International Nuclear Information System (INIS)

    Sokoloff, L.

    1985-01-01

    This book is a survey of the applications of imaging studies of regional cerebral blood flow and metabolism to the investigation of neurological and psychiatric disorders. Contributors review imaging techniques and strategies for measuring regional cerebral blood flow and metabolism, for mapping functional neural systems, and for imaging normal brain functions. They then examine the applications of brain imaging techniques to the study of such neurological and psychiatric disorders as: cerebral ischemia; convulsive disorders; cerebral tumors; Huntington's disease; Alzheimer's disease; depression and other mood disorders. A state-of-the-art report on magnetic resonance imaging of the brain and central nervous system rounds out the book's coverage

  8. Neurosteroid Transport in the Brain: Role of ABC and SLC Transporters

    Directory of Open Access Journals (Sweden)

    Markus Grube

    2018-04-01

    Full Text Available Neurosteroids, comprising pregnane, androstane, and sulfated steroids can alter neuronal excitability through interaction with ligand-gated ion channels and other receptors and have therefore a therapeutic potential in several brain disorders. They can be formed in brain cells or are synthesized by an endocrine gland and reach the brain by penetrating the blood–brain barrier (BBB. Especially sulfated steroids such as pregnenolone sulfate (PregS and dehydroepiandrosterone sulfate (DHEAS depend on transporter proteins to cross membranes. In this review, we discuss the involvement of ATP-binding cassette (ABC- and solute carrier (SLC-type membrane proteins in the transport of these compounds at the BBB and in the choroid plexus (CP, but also in the secretion from neurons and glial cells. Among the ABC transporters, especially BCRP (ABCG2 and several MRP/ABCC subfamily members (MRP1, MRP4, MRP8 are expressed in the brain and known to efflux conjugated steroids. Furthermore, several SLC transporters have been shown to mediate cellular uptake of steroid sulfates. These include members of the OATP/SLCO subfamily, namely OATP1A2 and OATP2B1, as well as OAT3 (SLC22A3, which have been reported to be expressed at the BBB, in the CP and in part in neurons. Furthermore, a role of the organic solute transporter OSTα-OSTβ (SLC51A/B in brain DHEAS/PregS homeostasis has been proposed. This transporter was reported to be localized especially in steroidogenic cells of the cerebellum and hippocampus. To date, the impact of transporters on neurosteroid homeostasis is still poorly understood. Further insights are desirable also with regard to the therapeutic potential of these compounds.

  9. The ischemic perinatal brain damage

    International Nuclear Information System (INIS)

    Crisi, G.; Mauri, C.; Canossi, G.; Della Giustina, E.

    1986-01-01

    The term ''hypoxic-ischemic encephalopathy'' covers a large part of neonatal neuropathology including the various forms of intracerebral haemorrhage. In the present work the term is confined to ischemic brain edema and actual infarction, be it diffuse or focal. Eighteen newborns with CT evidence of ischemic brain lesions and infarctual necrosis were selected. Emphasis is placed on current data on neuropathology of ischemic brain edema and its CT appearance. Particular entities such as periventricular leukomalacia and multicystic encephalopathy are discussed. Relationship between CT and temporal profile of cerebral damage is emphasized in order to predict the structural sequelae and the longterm prognosis

  10. Role of surgery in brain metastases.

    Science.gov (United States)

    Laghari, Altaf Ali; Ahmed, Syed Ijlal; Shamim, Muhammad Shahzad

    2017-08-01

    Brain metastases remain the commonest type of brain tumour, being four times more common than primary brain tumours. Although surgical intervention may be recommended for one of various reasons in the management of these tumours, including but not limited to conformation of diagnosis, relief of mass effect, improvement of neurological status and prolongation of survival, the guidelines for management of brain metastases remain largely subjective and therefore controversial. Herein the authors have attempted to review some of the existing evidence on role of surgery in the management of brain metastases and have presented their selected guidelines for the readers.

  11. Brain SPECT

    International Nuclear Information System (INIS)

    Feistel, H.

    1991-01-01

    Brain SPECT investigations have gained broad acceptance since the introduction of the lipophilic tracer Tc-99m-HMPAO. Depending on equipment and objectives in different departments, the examinations can be divided into three groups: 1. Under normal conditions and standardised patient preparation the 'rest' SPECT can be performed in every department with a tomographic camera. In cerebrovascular disease there is a demand for determination of either the perfusion reserve in reversible ischemia or prognostic values in completed stroke. In cases of dementia, SPECT may yield useful results according to differential diagnosis. Central cerebral system involvement in immunologic disease may be estimated with higher sensitivity than in conventional brain imaging procedures. In psychiatric diseases there is only a relative indication for brain SPECT, since results during recent years have been contradictory and may be derived only in interventional manner. In brain tumor diagnostics SPECT with Tl-201 possibly permits grading. In inflammatory disease, especially in viral encephalitis, SPECT may be used to obtain early diagnosis. Normal pressure hydrocephalus can be distinguished from other forms of dementia and, consequently, the necessity for shunting surgery can be recognised. 2. In departments equipped for emergency cases an 'acute' SPECT can be performed in illnesses with rapid changing symptoms such as different forms of migraine, transient global amnesia, epileptic seizures (so-called 'ictal SPECT') or urgent forms like trauma. 3. In cooperation with several departments brain SPECT can be practised as an interventional procedure in clinical and in scientific studies. (orig./MG) [de

  12. Selective Audiovisual Semantic Integration Enabled by Feature-Selective Attention.

    Science.gov (United States)

    Li, Yuanqing; Long, Jinyi; Huang, Biao; Yu, Tianyou; Wu, Wei; Li, Peijun; Fang, Fang; Sun, Pei

    2016-01-13

    An audiovisual object may contain multiple semantic features, such as the gender and emotional features of the speaker. Feature-selective attention and audiovisual semantic integration are two brain functions involved in the recognition of audiovisual objects. Humans often selectively attend to one or several features while ignoring the other features of an audiovisual object. Meanwhile, the human brain integrates semantic information from the visual and auditory modalities. However, how these two brain functions correlate with each other remains to be elucidated. In this functional magnetic resonance imaging (fMRI) study, we explored the neural mechanism by which feature-selective attention modulates audiovisual semantic integration. During the fMRI experiment, the subjects were presented with visual-only, auditory-only, or audiovisual dynamical facial stimuli and performed several feature-selective attention tasks. Our results revealed that a distribution of areas, including heteromodal areas and brain areas encoding attended features, may be involved in audiovisual semantic integration. Through feature-selective attention, the human brain may selectively integrate audiovisual semantic information from attended features by enhancing functional connectivity and thus regulating information flows from heteromodal areas to brain areas encoding the attended features.

  13. Epilepsy and brain tumors

    Science.gov (United States)

    ENGLOT, DARIO J.; CHANG, EDWARD F.; VECHT, CHARLES J.

    2016-01-01

    Seizures are common in patients with brain tumors, and epilepsy can significantly impact patient quality of life. Therefore, a thorough understanding of rates and predictors of seizures, and the likelihood of seizure freedom after resection, is critical in the treatment of brain tumors. Among all tumor types, seizures are most common with glioneuronal tumors (70–80%), particularly in patients with frontotemporal or insular lesions. Seizures are also common in individuals with glioma, with the highest rates of epilepsy (60–75%) observed in patients with low-grade gliomas located in superficial cortical or insular regions. Approximately 20–50% of patients with meningioma and 20–35% of those with brain metastases also suffer from seizures. After tumor resection, approximately 60–90% are rendered seizure-free, with most favorable seizure outcomes seen in individuals with glioneuronal tumors. Gross total resection, earlier surgical therapy, and a lack of generalized seizures are common predictors of a favorable seizure outcome. With regard to anticonvulsant medication selection, evidence-based guidelines for the treatment of focal epilepsy should be followed, and individual patient factors should also be considered, including patient age, sex, organ dysfunction, comorbidity, or cotherapy. As concomitant chemotherapy commonly forms an essential part of glioma treatment, enzyme-inducing anticonvulsants should be avoided when possible. Seizure freedom is the ultimate goal in the treatment of brain tumor patients with epilepsy, given the adverse effects of seizures on quality of life. PMID:26948360

  14. Radiosurgery for brain metastases: is whole brain radiotherapy necessary?

    International Nuclear Information System (INIS)

    Sneed, Penny K.; Lamborn, Kathleen R.; Forstner, Julie M.; McDermott, Michael W.; Chang, Susan; Park, Elaine; Gutin, Philip H.; Phillips, Theodore L.; Wara, William M.; Larson, David A.

    1999-01-01

    Purpose: Because whole brain radiotherapy (WBRT) may cause dementia in long-term survivors, selected patients with brain metastases may benefit from initial treatment with radiosurgery (RS) alone reserving WBRT for salvage as needed. We reviewed results of RS ± WBRT in patients with newly diagnosed brain metastasis to provide background for a prospective trial. Methods and Materials: Patients with single or multiple brain metastases managed initially with RS alone vs. RS + WBRT (62 vs. 43 patients) from 1991 through February 1997 were retrospectively reviewed. The use of upfront WBRT depended on physician preference and referral patterns. Survival, freedom from progression (FFP) endpoints, and brain control allowing for successful salvage therapy were measured from the date of diagnosis of brain metastases. Actuarial curves were estimated using the Kaplan-Meier method. Analyses to adjust for known prognostic factors were performed using the Cox proportional hazards model (CPHM) stratified by primary site. Results: Survival and local FFP were the same for RS alone vs. RS + WBRT (median survival 11.3 vs. 11.1 months and 1-year local FFP by patient 71% vs. 79%, respectively). Brain FFP (scoring new metastases and/or local failure) was significantly worse for RS alone vs. RS + WBRT (28% vs. 69% at 1 year; CPHM adjusted p = 0.03 and hazard ratio = 0.476). However, brain control allowing for successful salvage of a first failure was not significantly different for RS alone vs. RS + WBRT (62% vs. 73% at 1 year; CPHM adjusted p = 0.56). Conclusions: The omission of WBRT in the initial management of patients treated with RS for up to 4 brain metastases does not appear to compromise survival or intracranial control allowing for salvage therapy as indicated. A randomized trial of RS vs. RS + WBRT is needed to assess survival, quality of life, and cost in good-prognosis patients with newly diagnosed brain metastases

  15. Distinct Neural-Functional Effects of Treatments With Selective Serotonin Reuptake Inhibitors, Electroconvulsive Therapy, and Transcranial Magnetic Stimulation and Their Relations to Regional Brain Function in Major Depression: A Meta-analysis.

    Science.gov (United States)

    Chau, David T; Fogelman, Phoebe; Nordanskog, Pia; Drevets, Wayne C; Hamilton, J Paul

    2017-05-01

    Functional neuroimaging studies have examined the neural substrates of treatments for major depressive disorder (MDD). Low sample size and methodological heterogeneity, however, undermine the generalizability of findings from individual studies. We conducted a meta-analysis to identify reliable neural changes resulting from different modes of treatment for MDD and compared them with each other and with reliable neural functional abnormalities observed in depressed versus control samples. We conducted a meta-analysis of studies reporting changes in brain activity (e.g., as indexed by positron emission tomography) following treatments with selective serotonin reuptake inhibitors (SSRIs), electroconvulsive therapy (ECT), or transcranial magnetic stimulation. Additionally, we examined the statistical reliability of overlap among thresholded meta-analytic SSRI, ECT, and transcranial magnetic stimulation maps as well as a map of abnormal neural function in MDD. Our meta-analysis revealed that 1) SSRIs decrease activity in the anterior insula, 2) ECT decreases activity in central nodes of the default mode network, 3) transcranial magnetic stimulation does not result in reliable neural changes, and 4) regional effects of these modes of treatment do not significantly overlap with each other or with regions showing reliable functional abnormality in MDD. SSRIs and ECT produce neurally distinct effects relative to each other and to the functional abnormalities implicated in depression. These treatments therefore may exert antidepressant effects by diminishing neural functions not implicated in depression but that nonetheless impact mood. We discuss how the distinct neural changes resulting from SSRIs and ECT can account for both treatment effects and side effects from these therapies as well as how to individualize these treatments. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Brain Fog

    Science.gov (United States)

    ... relationship with your doctor(s): • Always report changes in cognition/memory and mood (depression, anxiety). • Make sure your physician ... joint pain. • Exercise regularly. Adequate physical exercise enhances cognition/memory. • Train the Brain! “If you don’t use ...

  17. Robot brains

    NARCIS (Netherlands)

    Babuska, R.

    2011-01-01

    The brain hosts complex networks of neurons that are responsible for behavior in humans and animals that we generally call intelligent. I is not easy to give an exact definition of intelligence – for the purpose of this talk it will suffice to say that we refer to intelligence as a collection of

  18. Analysis of the gene coding for steroidogenic factor 1 (SF1, NR5A1) in a cohort of 50 Egyptian patients with 46,XY disorders of sex development.

    Science.gov (United States)

    Tantawy, Sally; Mazen, Inas; Soliman, Hala; Anwar, Ghada; Atef, Abeer; El-Gammal, Mona; El-Kotoury, Ahmed; Mekkawy, Mona; Torky, Ahmad; Rudolf, Agnes; Schrumpf, Pamela; Grüters, Annette; Krude, Heiko; Dumargne, Marie-Charlotte; Astudillo, Rebekka; Bashamboo, Anu; Biebermann, Heike; Köhler, Birgit

    2014-05-01

    Steroidogenic factor 1 (SF1, NR5A1) is a key transcriptional regulator of genes involved in the hypothalamic-pituitary-gonadal axis. Recently, SF1 mutations were found to be a frequent cause of 46,XY disorders of sex development (DSD) in humans. We investigate the frequency of NR5A1 mutations in an Egyptian cohort of XY DSD. Clinical assessment, endocrine evaluation and genetic analysis of 50 Egyptian XY DSD patients (without adrenal insufficiency) with a wide phenotypic spectrum. Molecular analysis of NR5A1 gene by direct sequencing followed by in vitro functional analysis of the two novel missense mutations detected. Three novel heterozygous mutations of the coding region in patients with hypospadias were detected. p.Glu121AlafsX25 results in severely truncated protein, p.Arg62Cys lies in DNA-binding zinc finger, whereas p.Ala154Thr lies in the hinge region of SF1 protein. Transactivation assays using reporter constructs carrying promoters of anti-Müllerian hormone (AMH), CYP11A1 and TESCO core enhancer of Sox9 showed that p.Ala154Thr and p.Arg62Cys mutations result in aberrant biological activity of NR5A1. A total of 17 patients (34%) harboured the p.Gly146Ala polymorphism. We identified two novel NR5A1 mutations showing impaired function in 23 Egyptian XY DSD patients with hypospadias (8.5%). This is the first study searching for NR5A1 mutations in oriental patients from the Middle East and Arab region with XY DSD and no adrenal insufficiency, revealing a frequency similar to that in European patients (6.5-15%). We recommend screening of NR5A1 in patients with hypospadias and gonadal dysgenesis. Yearly follow-ups of gonadal function and early cryoconservation of sperms should be performed in XY DSD patients with NR5A1 mutations given the risk of future fertility problems due to early gonadal failure.

  19. Understanding Brain Tumors

    Science.gov (United States)

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  20. Brain tumor - children

    Science.gov (United States)

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  1. Brain Tumors (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Brain Tumors KidsHealth / For Parents / Brain Tumors What's in ... radiation therapy or chemotherapy, or both. Types of Brain Tumors There are many different types of brain ...

  2. Brain and Nervous System

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Brain and Nervous System KidsHealth / For Parents / Brain and ... healthy, and remove waste products. All About the Brain The brain is made up of three main ...

  3. The Creative Brain.

    Science.gov (United States)

    Herrmann, Ned

    1982-01-01

    Outlines the differences between left-brain and right-brain functioning and between left-brain and right-brain dominant individuals, and concludes that creativity uses both halves of the brain. Discusses how both students and curriculum can become more "whole-brained." (Author/JM)

  4. Brain imaging

    International Nuclear Information System (INIS)

    Greenfield, L.D.; Bennett, L.R.

    1976-01-01

    Imaging with radionuclides should be used in a complementary fashion with other neuroradiologic techniques. It is useful in the early detection and evaluation of intracranial neoplasm, cerebrovascular accident and abscess, and in postsurgical follow-up. Cisternography yields useful information about the functional status of cerebrospinal fluid pathways. Computerized axial tomography is a new technique of great promise that produced a cross-sectional image of the brain

  5. Brain imaging

    International Nuclear Information System (INIS)

    Bradshaw, J.R.

    1989-01-01

    This book presents a survey of the various imaging tools with examples of the different diseases shown best with each modality. It includes 100 case presentations covering the gamut of brain diseases. These examples are grouped according to the clinical presentation of the patient: headache, acute headache, sudden unilateral weakness, unilateral weakness of gradual onset, speech disorders, seizures, pituitary and parasellar lesions, sensory disorders, posterior fossa and cranial nerve disorders, dementia, and congenital lesions

  6. Radiosurgery for brain metastases: is whole brain radiation therapy necessary?

    International Nuclear Information System (INIS)

    Forstner, Julie M.; Sneed, Penny K.; Lamborn, Kathleen R.; Shu, H.-K.G.; McDermott, Michael W.; Park, Elaine; Ho, Maria; Chang, Susan; Gutin, Philip H.; Phillips, Theodore L.; Wara, William M.; Larson, David A.

    1996-01-01

    , (12(33)) patients (36%) failed in the brain and (18(33)) (55%) died without evidence of brain failure. New metastases developed in (16(54)) patients treated with RS alone vs. (9(33)) patients treated with RS + WBRT (29% vs. 27%). Treated metastases progressed in (10(54)) patients who had RS alone vs. (9(33)) patients who had RS + WBRT (19% vs. 15%). Ten patients received salvage WBRT. For the 47 patients with solitary lesions, there was no significant difference in Brain FFP or survival for RS + WBRT vs. RS alone, although patients appeared to fail earlier in the RS alone group. For the 40 patients with multiple lesions, there was a definite trend toward improved Brain FFP for RS + WBRT vs. RS alone, but there was no suggestion of a survival difference. Cox multivariate analyses adjusting for known prognostic factors confirmed these findings. Conclusion: Whole brain radiation therapy may not be necessary in the initial management of patients treated with RS for brain metastases, because the omission of WBRT has limited impact on Brain FFP and does not seem to compromise survival. We attempted to adjust for important prognostic variables in this retrospective review, but there could have been a bias toward giving WBRT in patients with poorer prognosis. To eliminate bias, a randomized trial of RS vs. RS + WBRT is needed to assess survival, quality of life, and cost in selected patients with newly diagnosed brain metastases. Quality of life evaluation is needed to assess the balance between the impact of possible WBRT toxicity and possible earlier intracranial failure associated with RS alone

  7. Brain abscess: a review | Magoha | East African Medical Journal

    African Journals Online (AJOL)

    Objective: To carry out a current review of brain abscess data source: review of all the published literature on the brain abscess until august 2016 was carried out through internet, google, pubmed and medline searches. Data selection: Published data on brain abscess were included in the review. Data extraction: Abstracts ...

  8. Molecular cloning and expression analysis of fushi tarazu factor 1 in the brain of air-breathing catfish, Clarias gariepinus.

    Directory of Open Access Journals (Sweden)

    Parikipandla Sridevi

    Full Text Available BACKGROUND: Fushi tarazu factor 1 (FTZ-F1 encodes an orphan nuclear receptor belonging to the nuclear receptor family 5A (NR5A which includes adrenal 4-binding protein or steroidogenic factor-1 (Ad4BP/SF-1 and liver receptor homologue 1 (LRH-1 and plays a pivotal role in the regulation of aromatases. METHODOLOGY/PRINCIPAL FINDINGS: Present study was aimed to understand the importance of FTZ-F1 in relation to brain aromatase (cyp19a1b during development, recrudescence and after human chorionic gonadotropin (hCG induction. Initially, we cloned FTZ-F1 from the brain of air-breathing catfish, Clarias gariepinus through degenerate primer RT-PCR and RACE. Its sequence analysis revealed high homology with other NR5A1 group members Ad4BP/SF-1 and LRH-1, and also analogous to the spatial expression pattern of the latter. In order to draw functional correlation of cyp19a1b and FTZ-F1, we analyzed the expression pattern of the latter in brain during gonadal ontogeny, which revealed early expression during gonadal differentiation. The tissue distribution both at transcript and protein levels revealed its prominent expression in brain along with liver, kidney and testis. The expression pattern of brain FTZ-F1 during reproductive cycle and after hCG induction, in vivo was analogous to that of cyp19a1b shown in our earlier study indicating its involvement in recrudescence. CONCLUSIONS/SIGNIFICANCE: Based on our previous results on cyp19a1b and the present data, it is plausible to implicate potential roles for brain FTZ-F1 in ovarian differentiation and recrudescence process probably through regulation of cyp19a1b in teleosts. Nevertheless, these interactions would require primary coordinated response from ovarian aromatase and its related transcription factors.

  9. The 2013 Discovery Award from the Society for Free Radical Biology and Medicine: Selected Discoveries from the Butterfield Laboratory of Oxidative Stress and Its Sequelae in Brain in Cognitive Disorders Exemplified by Alzheimer Disease and Chemotherapy Induced Cognitive Impairment

    Science.gov (United States)

    Butterfield, D. Allan

    2014-01-01

    This retrospective review on discoveries of the roles of oxidative stress in brain of subjects with Alzheimer disease (AD) and animal models thereof as well as brain from animal models of chemotherapy induced cognitive impairment (CICI) results from the author receiving the 2013 Discovery Award from the Society for Free Radical Biology and Medicine. The paper reviews our laboratory's discovery of: protein oxidation and lipid peroxidation in AD brain regions rich in amyloid β-peptide (Aβ) but not in Aβ-poor cerebellum; redox proteomics as a means to identify oxidatively modified brain proteins in AD and its earlier forms that are consistent with the pathology, biochemistry, and clinical presentation of these disorders; how Aβ in in vivo, ex vivo, and in vitro studies can lead to oxidative modification of key proteins that also are oxidatively modified in AD brain; the role of the single methionine residue of Aβ(1-42) in these processes; and some of the potential mechanisms in the pathogenesis and progression of AD. CICI affects a significant fraction of the 14 million American cancer survivors, and due to diminished cognitive function, reduced quality of life of the persons with CICI (called “chemobrain” by patients) often results. A proposed mechanism for CICI employed the prototypical ROS-generating and non-blood brain barrier (BBB)-penetrating chemotherapeutic agent doxorubicin (Dox, also called adriamycin, ADR). Because of the quinone moiety within the structure of Dox, this agent undergoes redox cycling to produce superoxide free radical peripherally. This, in turn, leads to oxidative modification of the key plasma protein, Apolipoprotein A1 (ApoA1). Oxidized ApoA1 leads to elevated peripheral TNFα, a pro-inflammatory cytokine that crosses the BBB to induce oxidative stress in brain parenchyma that affects negatively brain mitochondria. This subsequently leads to apoptotic cell death resulting in CICI. This review outlines aspects of CICI consistent

  10. Targeting the Brain with Nanomedicine.

    Science.gov (United States)

    Rueda, Felix; Cruz, Luis J

    2017-01-01

    Herein, we review innovative nanomedicine-based approaches for treating, preventing and diagnosing neurodegenerative diseases. We focus on nanoscale systems such as polymeric nanoparticles (NPs), liposomes, micelles and other vehicles (e.g. dendrimers, nanogels, nanoemulsions and nanosuspensions) for targeted delivery of bioactive molecules to the brain. To ensure maximum selectivity for optimal therapeutic or diagnostic results, researchers must employ delivery systems that are non-toxic, biodegradable and biocompatible. This entails: (i) use of "safe" materials, such as polymers or lipids; (ii) targeting to the brain and, specifically, to the desired active site within the brain; (iii) controlled release of the loaded agent; and (iv) use of agents that, once released into the brain, will exhibit the desired pharmacologic activity. Here, we explore the design and preclinical use of representative delivery systems that have been proposed to date. We then analyze the principal challenges that have delayed clinical application of these and other approaches. Lastly, we look at future developments in this area, addressing the needs for increased penetration of the blood brain barrier (BBB), enhanced targeting of specific brain sites, improved therapeutic efficacy and lower neurotoxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Anti-amyloid beta protein antibody passage across the blood-brain barrier in the SAMP8 mouse model of Alzheimer's disease: an age-related selective uptake with reversal of learning impairment.

    Science.gov (United States)

    Banks, William A; Farr, Susan A; Morley, John E; Wolf, Kathy M; Geylis, Valeria; Steinitz, Michael

    2007-08-01

    Amyloid beta protein (Abeta) levels are elevated in the brain of Alzheimer's disease patients. Anti-Abeta antibodies can reverse the histologic and cognitive impairments in mice which overexpress Abeta. Passive immunization appears safer than vaccination and treatment of patients will likely require human rather than xenogenic antibodies. Effective treatment will likely require antibody to cross the blood-brain barrier (BBB). Unfortunately, antibodies typically cross the BBB very poorly and accumulate less well in brain than even albumin, a substance nearly totally excluded from the brain. We compared the ability of two anti-Abeta human monoclonal IgM antibodies, L11.3 and HyL5, to cross the BBB of young CD-1 mice to that of young and aged SAMP8 mice. The SAMP8 mouse has a spontaneous mutation that induces an age-related, Abeta-dependent cognitive deficit. There was preferential uptake of intravenously administered L11.3 in comparison to HyL5, albumin, and a control human monoclonal IgM (RF), especially by hippocampus and olfactory bulb in aged SAMP8 mice. Injection of L11.3 into the brains of aged SAMP8 mice reversed both learning and memory impairments in aged SAMP8 mice, whereas IgG and IgM controls were ineffective. Pharmacokinetic analysis predicted that an intravenous dose 1000 times higher than the brain injection dose would reverse cognitive impairments. This predicted intravenous dose reversed the impairment in learning, but not memory, in aged SAMP8 mice. In conclusion, an IgM antibody was produced that crosses the BBB to reverse cognitive impairment in a murine model of Alzheimer's disease.

  12. NIH Conference. Brain imaging: aging and dementia

    International Nuclear Information System (INIS)

    Cutler, N.R.; Duara, R.; Creasey, H.; Grady, C.L.; Haxby, J.V.; Schapiro, M.B.; Rapoport, S.I.

    1984-01-01

    The brain imaging techniques of positron emission tomography using [18F]-fluoro-2-deoxy-D-glucose, and computed tomography, together with neuropsychological tests, were used to examine overall brain function and anatomy in three study populations: healthy men at different ages, patients with presumptive Alzheimer's disease, and adults with Down's syndrome. Brain glucose use did not differ with age, whereas an age-related decrement in gray matter volume was found on computed tomographic assessment in healthy subjects. Memory deficits were found to precede significant reductions in brain glucose utilization in mild to moderate Alzheimer's dementia. Furthermore, differences between language and visuoconstructive impairments in patients with mild to moderate Alzheimer's disease were related to hemispheric asymmetry of brain metabolism. Brain glucose utilization was found to be significantly elevated in young adults with Down's syndrome, compared with controls. The importance of establishing strict criteria for selecting control subjects and patients is explained in relation to the findings

  13. The Blood-Brain Barrier: Connecting the Gut and the Brain

    OpenAIRE

    Banks, William A.

    2008-01-01

    The BBB prevents the unrestricted exchange of substances between the central nervous system (CNS) and the blood. The blood-brain barrier (BBB) also conveys information between the CNS and the gastrointestinal (GI) tract through several mechanisms. Here, we review three of those mechanisms. First, the BBB selectively transports some peptides and regulatory proteins in the blood-to-brain or the brain-to-blood direction. The ability of GI hormones to affect functions of the BBB, as illustrated b...

  14. Whole-brain dynamic CT angiography and perfusion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Orrison, W.W. [CHW Nevada Imaging Company, Nevada Imaging Centers, Spring Valley, Las Vegas, NV (United States); College of Osteopathic Medicine, Touro University Nevada, Henderson, NV (United States); Department of Health Physics and Diagnostic Sciences, University of Nevada Las Vegas, Las Vegas, NV (United States); Department of Medical Education, University of Nevada School of Medicine, Reno, NV (United States); Snyder, K.V.; Hopkins, L.N. [Department of Neurosurgery, Millard Fillmore Gates Circle Hospital, Buffalo, NY (United States); Roach, C.J. [School of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV (United States); Advanced Medical Imaging and Genetics (Amigenics), Las Vegas, NV (United States); Ringdahl, E.N. [Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV (United States); Nazir, R. [Shifa International Hospital, Islamabad (Pakistan); Hanson, E.H., E-mail: eric.hanson@amigenics.co [College of Osteopathic Medicine, Touro University Nevada, Henderson, NV (United States); Department of Health Physics and Diagnostic Sciences, University of Nevada Las Vegas, Las Vegas, NV (United States); Advanced Medical Imaging and Genetics (Amigenics), Las Vegas, NV (United States)

    2011-06-15

    The availability of whole brain computed tomography (CT) perfusion has expanded the opportunities for analysing the haemodynamic parameters associated with varied neurological conditions. Examples demonstrating the clinical utility of whole-brain CT perfusion imaging in selected acute and chronic ischaemic arterial neurovascular conditions are presented. Whole-brain CT perfusion enables the detection and focused haemodynamic analyses of acute and chronic arterial conditions in the central nervous system without the limitation of partial anatomical coverage of the brain.

  15. Baby Brain Map

    Science.gov (United States)

    ... a Member Home Resources & Services Professional Resource Baby Brain Map Mar 17, 2016 The Brain Map was adapted in 2006 by ZERO TO ... supports Adobe Flash Player. To view the Baby Brain Map, please visit this page on a browser ...

  16. Pediatric Brain Tumor Foundation

    Science.gov (United States)

    ... navigate their brain tumor diagnosis. WATCH AND SHARE Brain tumors and their treatment can be deadly so ... Pediatric Central Nervous System Cancers Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  17. That's Using Your Brain!

    Science.gov (United States)

    Visser, Dana R.

    1996-01-01

    Discusses new adult learning theories, including those of Roger Sperry (left brain/right brain), Paul McLean (triune brain), and Howard Gardner (multiple intelligences). Relates adult learning theory to training. (JOW)

  18. Brain SPECT in children

    International Nuclear Information System (INIS)

    Guyot, M.; Baulieu, J.L.

    1996-01-01

    Brain SPECT in child involves specific trends regarding the patient cooperation, irradiation, resolution and especially interpretation because of the rapid scintigraphic modifications related to the brain maturation. In a general nuclear medicine department, child brain SPECT represents about 2 % of the activity. The choice indications are the perfusion children: thallium and MIBI in brain tumours, pharmacological and neuropsychological interventions. In the future, brain dedicated detectors and new radiopharmaceuticals will promote the development of brain SPECT in children. (author)

  19. Revisiting Einstein's brain in Brain Awareness Week.

    Science.gov (United States)

    Chen, Hao; Chen, Su; Zeng, Lidan; Zhou, Lin; Hou, Shengtao

    2014-10-01

    Albert Einstein's brain has long been an object of fascination to both neuroscience specialists and the general public. However, without records of advanced neuro-imaging of his brain, conclusions regarding Einstein's extraordinary cognitive capabilities can only be drawn based on the unique external features of his brain and through comparison of the external features with those of other human brain samples. The recent discovery of 14 previously unpublished photographs of Einstein's brain taken at unconventional angles by Dr. Thomas Stoltz Harvey, the pathologist, ignited a renewed frenzy about clues to explain Einstein's genius. Dr. Dean Falk and her colleagues, in their landmark paper published in Brain (2013; 136:1304-1327), described in such details about the unusual features of Einstein's brain, which shed new light on Einstein's intelligence. In this article, we ask what are the unique structures of his brain? What can we learn from this new information? Can we really explain his extraordinary cognitive capabilities based on these unique brain structures? We conclude that studying the brain of a remarkable person like Albert Einstein indeed provides us a better example to comprehensively appreciate the relationship between brain structures and advanced cognitive functions. However, caution must be exercised so as not to over-interpret his intelligence solely based on the understanding of the surface structures of his brain.

  20. Peripheral benzodiazepines receptor (PBR stimulates steroidogenesis: A potential neuroprotective pathway following brain damage

    Directory of Open Access Journals (Sweden)

    George E. Barreto

    2015-04-01

    Full Text Available The effects of neuroactive steroids have been highly assessed for their significance on inflammation resolution induced by cytotoxic agents. Steroids are derived from cholesterol, and this regulatory pathway may be a target for possible protective strategies. For example, the increased expression of peripheral benzodiazepine receptor (PBR stimulates steroids production, and the action of specific ligands on PBR favors the reduction of glial activity and act as a protective mechanism. The augmented expression of PBR and steroidogenic acute regulatory protein (StAR after injury is associated with local production of steroids by glial cells. For instance, cholesterol is captured by StAR in the outer mitochondrial membrane that transfers it to PBR, which uses it as substrate for the enzyme P450scc in the inner mitochondrial membrane. Some ligands, such as 4'-Chlorodiazepam (Ro5-4864 and isoquinoline carboxamide (PK 11195, act as agonists of the PBR receptor. Previous studies indicate that Ro5-4864 reduces neuronal loss, thus implying the regulation of mitochondrial transition after a traumatic brain injury. In this work, we assess the effects of PBR ligands directly involved in neuronal cell survival and proliferation after injury, thereby activating potential downstream targets as novel therapeutic approaches.

  1. Left brain, right brain: facts and fantasies.

    Science.gov (United States)

    Corballis, Michael C

    2014-01-01

    Handedness and brain asymmetry are widely regarded as unique to humans, and associated with complementary functions such as a left-brain specialization for language and logic and a right-brain specialization for creativity and intuition. In fact, asymmetries are widespread among animals, and support the gradual evolution of asymmetrical functions such as language and tool use. Handedness and brain asymmetry are inborn and under partial genetic control, although the gene or genes responsible are not well established. Cognitive and emotional difficulties are sometimes associated with departures from the "norm" of right-handedness and left-brain language dominance, more often with the absence of these asymmetries than their reversal.

  2. Traumatic brain lesions in newborns

    Directory of Open Access Journals (Sweden)

    Nícollas Nunes Rabelo

    Full Text Available ABSTRACT The neonatal period is a highly vulnerable time for an infant. The high neonatal morbidity and mortality rates attest to the fragility of life during this period. The incidence of birth trauma is 0.8%, varying from 0.2-2 per 1,000 births. The aim of this study is to describe brain traumas, and their mechanism, anatomy considerations, and physiopathology of the newborn traumatic brain injury. Methods A literature review using the PubMed data base, MEDLINE, EMBASE, Science Direct, The Cochrane Database, Google Scholar, and clinical trials. Selected papers from 1922 to 2016 were studied. We selected 109 papers, through key-words, with inclusion and exclusion criteria. Discussion This paper discusses the risk factors for birth trauma, the anatomy of the occipito-anterior and vertex presentation, and traumatic brain lesions. Conclusion Birth-related traumatic brain injury may cause serious complications in newborn infants. Its successful management includes special training, teamwork, and an individual approach.

  3. 1-[3-(4-Butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1) as a Model for the Rational Design of a Novel Class of Brain Penetrant Ligands with High Affinity and Selectivity for Dopamine D4 Receptor.

    Science.gov (United States)

    Del Bello, Fabio; Bonifazi, Alessandro; Giorgioni, Gianfabio; Cifani, Carlo; Micioni Di Bonaventura, Maria Vittoria; Petrelli, Riccardo; Piergentili, Alessandro; Fontana, Stefano; Mammoli, Valerio; Yano, Hideaki; Matucci, Rosanna; Vistoli, Giulio; Quaglia, Wilma

    2018-04-26

    In the present article, the M 1 mAChR bitopic agonist 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1, 1) has been demonstrated to show unexpected D 4 R selectivity over D 2 R and D 3 R and to behave as a D 4 R antagonist. To better understand the structural features required for the selective interaction with the D 4 R and to obtain compounds unable to activate mAChRs, the aliphatic butyl chain and the piperidine nucleus of 1 were modified, affording compounds 2-14. The 4-benzylpiperidine 9 and the 4-phenylpiperazine 12 showed high D 4 R affinity and selectivity not only over the other D 2 -like subtypes, but also over M 1 -M 5 mAChRs. Derivative 12 was also highly selective over some selected off-targets. This compound showed biased behavior, potently and partially activating G i protein and inhibiting β-arrestin2 recruitment in functional studies. Pharmacokinetic studies demonstrated that it was characterized by a relevant brain penetration. Therefore, 12 might be a useful tool to better clarify the role played by D 4 R in disorders in which this subtype is involved.

  4. Quantitative Autoradiography on [(35)S]TBPS Binding Sites of Gamma- Aminobutyric Acid(A) Receptors in Discrete Brain Regions of High- Alcohol-Drinking and Low-Alcohol- Drinking Rats Selectively Bred forHigh- and Low-Alcohol Preference.

    Science.gov (United States)

    Hwang, B.H.; Kunkler, P.E.; Lumeng, L.

    1997-01-01

    It has been documented that ethanol can potentiate brain gamma-aminobutyric acid (GABA)ergic function, and there is a close link between the GABA(A) receptor complex and effects of ethanol, including reinforcement of alcohol which is a fundamental element of alcohol preference. However, it is unknown in what discrete brain regions GABA(A) receptors might be associated with alcohol preference. In the present study, [(35)S]t-butylbicyclophosphorothionate ([(35)S]TBPS) was used to localize GABA(A) receptors in high-alcohol-drinking (HAD) rats and low-alcohol-drinking (LAD) rats which were selectively bred for high and low alcohol preference, respectively. Initial qualitative observations indicated that [(35)S]TBPS binding sites were abundant in many brain areas including the cerebral cortex, hypothalamus and amygdala of HAD and LAD rats. Furthermore, the quantitative autoradiographic analysis revealed fewer [(35)S]TBPS binding sites of GABA(A) receptors in the amygdaloid complex, central medial thalamic nucleus, lateral hypothalamic nucleus and anterior hypothalamic nucleus of HAD rats than LAD rats. Collectively, this study has indicated that HAD rats selectively bred for high alcohol preference possess lower [(35)S]TBPS binding in the brain. Since lower TBPS binding has been proposed to reflect enhanced GABAergic function, as evidenced in rats with seizure or under alcohol withdrawal, the results from the present study suggest that HAD rats might have an enhanced GABAergic function. It is thus likely that enhanced GABAergic function in the brain might be related to high alcohol preference which is characteristic in HAD rats. In addition, the present result showing no difference of [(35)S]TBPS binding in the nucleus accumbens is also in agreement with a notion that [(35)S]TBPS binding may represent only a small spectrum of the GABA(A) receptor complex which is constituted of a sophisticated subunit combination whose functional compositions are still unknown. In

  5. Assessment of Mexican Arnica (Heterotheca inuloides Cass) and Rosemary (Rosmarinus officinalis) Extracts on Dopamine and Selected Biomarkers of Oxidative Stress in Stomach and Brain of Salmonella typhimurium Infected rats.

    Science.gov (United States)

    Guzmàn, David Calderón; Herrera, Maribel Ortiz; Brizuela, Norma Osnaya; Mejía, Gerardo Barragàn; García, Ernestina Hernàndez; Olguín, Hugo Juàrez; Peraza, Armando Valenzuela; Ruíz, Norma Labra; Del Angel, Daniel Santamaría

    2017-01-01

    The effects of some natural products on dopamine (DA) and 5-hydroxyindole acetic acid (5-HIAA) in brain of infected models are still unclear. The purpose of this study was to measure the effect of Mexican arnica/rosemary (MAR) water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. Female Wistar rats (weight 80 g) in the presence of MAR or absence (no-MAR) were treated as follows: group 1, buffer solution (controls); oseltamivir (100 mg/kg), group 2; culture of Salmonella typhimurium ( S.Typh ) (1 × 10 6 colony-forming units/rat) group 3; oseltamivir (100 mg/kg) + S.Typh (same dose) group 4. Drug and extracts were administered intraperitoneally every 24 h for 5 days, and S.Typh was given orally on days 1 and 3. On the fifth day, blood was collected to measure glucose and hemoglobin. The brains and stomachs were obtained to measure levels of DA, 5-HIAA, glutathione (GSH), TBARS, H 2 O 2 , and total ATPase activity using validated methods. DA levels increased in MAR group treated with oseltamivir alone but decreased in no-MAR group treated with oseltamivir plus S.Typh . 5-HIAA, GSH, and H 2 O 2 decreased in this last group, and ATPase activity increased in MAR group treated with oseltamivir plus S.Typh . TBARS (lipid peroxidation) increased in MAR group that received oseltamivir alone. Most of the biomarkers were not altered significantly in the stomach. MAR extract alters DA and metabolism of 5-HIAA in the brain of young animals infected. Antioxidant capacity may be involved in these effects. The purpose of this study was to measure the effect of Mexican arnica/rosemary water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. Results: Mexican arnica and rosemary extract alter dopamine and metabolism of 5-HIAA in the brain of young animals infected. Antioxidant capacity may be

  6. /sup 3/H)-(H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2) ((/sup 3/H)CTOP), a potent and highly selective peptide for mu opioid receptors in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Hawkins, K.N.; Knapp, R.J.; Lui, G.K.; Gulya, K.; Kazmierski, W.; Wan, Y.P.; Pelton, J.T.; Hruby, V.J.; Yamamura, H.I.

    1989-01-01

    The cyclic, conformationally restricted octapeptide (3H)-(H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2) ((3H)CTOP) was synthesized and its binding to mu opioid receptors was characterized in rat brain membrane preparations. Association rates (k+1) of 1.25 x 10(8) M-1 min-1 and 2.49 x 10(8) M-1 min-1 at 25 and 37 degrees C, respectively, were obtained, whereas dissociation rates (k-1) at the same temperatures were 1.93 x 10(-2) min-1 and 1.03 x 10(-1) min-1 at 25 and 37 degrees C, respectively. Saturation isotherms of (3H)CTOP binding to rat brain membranes gave apparent Kd values of 0.16 and 0.41 nM at 25 and 37 degrees C, respectively. Maximal number of binding sites in rat brain membranes were found to be 94 and 81 fmol/mg of protein at 25 and 37 degrees C, respectively. (3H)CTOP binding over a concentration range of 0.1 to 10 nM was best fit by a one site model consistent with binding to a single site. The general effect of different metal ions and guanyl-5'-yl-imidodiphosphate on (3H)CTOP binding was to reduce its affinity. High concentrations (100 mM) of sodium also produced a reduction of the apparent mu receptor density. Utilizing the delta opioid receptor specific peptide (3H)-(D-Pen2,D-Pen5)enkephalin, CTOP appeared to be about 2000-fold more specific for mu vs. delta opioid receptor than naloxone. Specific (3H)CTOP binding was inhibited by a large number of opioid or opiate ligands.

  7. Detailed characterization of the in vitro pharmacological and pharmacokinetic properties of N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine (25CN-NBOH), a highly selective and brain-penetrant 5-HT2A receptor agonist

    DEFF Research Database (Denmark)

    Jensen, Anders A; McCorvy, John D; Petersen, Sebastian Leth

    2017-01-01

    ]ketanserin/[3H]mesulergine, [3H]LSD and [3H]Cimbi-36 binding assays (Ki 2C/Ki 2A ratio range 52-81, Ki 2B/Ki 2A ratio 37). Moreover, in inositol phosphate and intracellular Ca2+ mobilization assays 25CN-NBOH exhibited 30- to 180-fold 5-HT2A/5-HT2C selectivities and 54-fold 5-HT2A/5-HT2B selectivity as measured...

  8. Brain Cancer—Patient Version

    Science.gov (United States)

    Brain cancer refers to growths of malignant cells in tissues of the brain. Tumors that start in the brain are called primary brain tumors. Tumors that spread to the brain are called metastatic brain tumors. Start here to find information on brain cancer treatment, research, and statistics.

  9. Neuroscience, brains, and computers

    Directory of Open Access Journals (Sweden)

    Giorno Maria Innocenti

    2013-07-01

    Full Text Available This paper addresses the role of the neurosciences in establishing what the brain is and how states of the brain relate to states of the mind. The brain is viewed as a computational deviceperforming operations on symbols. However, the brain is a special purpose computational devicedesigned by evolution and development for survival and reproduction, in close interaction with theenvironment. The hardware of the brain (its structure is very different from that of man-made computers.The computational style of the brain is also very different from traditional computers: the computationalalgorithms, instead of being sets of external instructions, are embedded in brain structure. Concerningthe relationships between brain and mind a number of questions lie ahead. One of them is why andhow, only the human brain grasped the notion of God, probably only at the evolutionary stage attainedby Homo sapiens.

  10. FROM BRAIN DRAIN TO BRAIN NETWORKING

    Directory of Open Access Journals (Sweden)

    Irina BONCEA

    2015-06-01

    Full Text Available Scientific networking is the most accessible way a country can turn the brain drain into brain gain. Diaspora’s members offer valuable information, advice or financial support from the destination country, without being necessary to return. This article aims to investigate Romania’s potential of turning brain drain into brain networking, using evidence from the medical sector. The main factors influencing the collaboration with the country of origin are investigated. The conclusions suggest that Romania could benefit from the diaspora option, through an active implication at institutional level and the implementation of a strategy in this area.

  11. Mindboggle: Automated brain labeling with multiple atlases

    International Nuclear Information System (INIS)

    Klein, Arno; Mensh, Brett; Ghosh, Satrajit; Tourville, Jason; Hirsch, Joy

    2005-01-01

    To make inferences about brain structures or activity across multiple individuals, one first needs to determine the structural correspondences across their image data. We have recently developed Mindboggle as a fully automated, feature-matching approach to assign anatomical labels to cortical structures and activity in human brain MRI data. Label assignment is based on structural correspondences between labeled atlases and unlabeled image data, where an atlas consists of a set of labels manually assigned to a single brain image. In the present work, we study the influence of using variable numbers of individual atlases to nonlinearly label human brain image data. Each brain image voxel of each of 20 human subjects is assigned a label by each of the remaining 19 atlases using Mindboggle. The most common label is selected and is given a confidence rating based on the number of atlases that assigned that label. The automatically assigned labels for each subject brain are compared with the manual labels for that subject (its atlas). Unlike recent approaches that transform subject data to a labeled, probabilistic atlas space (constructed from a database of atlases), Mindboggle labels a subject by each atlas in a database independently. When Mindboggle labels a human subject's brain image with at least four atlases, the resulting label agreement with coregistered manual labels is significantly higher than when only a single atlas is used. Different numbers of atlases provide significantly higher label agreements for individual brain regions. Increasing the number of reference brains used to automatically label a human subject brain improves labeling accuracy with respect to manually assigned labels. Mindboggle software can provide confidence measures for labels based on probabilistic assignment of labels and could be applied to large databases of brain images

  12. Phosphatidylserine and the human brain.

    Science.gov (United States)

    Glade, Michael J; Smith, Kyl

    2015-06-01

    The aim of this study was to assess the roles and importance of phosphatidylserine (PS), an endogenous phospholipid and dietary nutrient, in human brain biochemistry, physiology, and function. A scientific literature search was conducted on MEDLINE for relevant articles regarding PS and the human brain published before June 2014. Additional publications were identified from references provided in original papers; 127 articles were selected for inclusion in this review. A large body of scientific evidence describes the interactions among PS, cognitive activity, cognitive aging, and retention of cognitive functioning ability. Phosphatidylserine is required for healthy nerve cell membranes and myelin. Aging of the human brain is associated with biochemical alterations and structural deterioration that impair neurotransmission. Exogenous PS (300-800 mg/d) is absorbed efficiently in humans, crosses the blood-brain barrier, and safely slows, halts, or reverses biochemical alterations and structural deterioration in nerve cells. It supports human cognitive functions, including the formation of short-term memory, the consolidation of long-term memory, the ability to create new memories, the ability to retrieve memories, the ability to learn and recall information, the ability to focus attention and concentrate, the ability to reason and solve problems, language skills, and the ability to communicate. It also supports locomotor functions, especially rapid reactions and reflexes. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Changes in Binding of [123I]CLINDE, a High-Affinity Translocator Protein 18 kDa (TSPO) Selective Radioligand in a Rat Model of Traumatic Brain Injury

    DEFF Research Database (Denmark)

    Donat, Cornelius K; Gaber, Khaled; Meixensberger, Jürgen

    2016-01-01

    , somatosensory and parietal cortex, as well as in the hippocampus and thalamus. Interestingly, binding was also significantly elevated in the contralateral M1 motor cortex following TBI. Craniotomy without TBI caused a less marked increase in [(123)I]CLINDE binding, restricted to the ipsilateral hemisphere...... studies using single-photon emission computed tomography to image the neuroinflammatory response after stroke. In this study, we used the same tracer in a rat model of TBI to determine changes in TSPO expression. Adult Sprague-Dawley rats were subjected to moderate controlled cortical impact injury...... and sacrificed at 6, 24, 72 h and 28 days post surgery. TSPO expression was assessed in brain sections employing [(123)I]CLINDE in vitro autoradiography. From 24 h to 28 days post surgery, injured animals exhibited a marked and time-dependent increase in [(123)I]CLINDE binding in the ipsilateral motor...

  14. Left brain, right brain: facts and fantasies.

    Directory of Open Access Journals (Sweden)

    Michael C Corballis

    2014-01-01

    Full Text Available Handedness and brain asymmetry are widely regarded as unique to humans, and associated with complementary functions such as a left-brain specialization for language and logic and a right-brain specialization for creativity and intuition. In fact, asymmetries are widespread among animals, and support the gradual evolution of asymmetrical functions such as language and tool use. Handedness and brain asymmetry are inborn and under partial genetic control, although the gene or genes responsible are not well established. Cognitive and emotional difficulties are sometimes associated with departures from the "norm" of right-handedness and left-brain language dominance, more often with the absence of these asymmetries than their reversal.

  15. Biomechanics of the brain

    CERN Document Server

    Miller, Karol

    2011-01-01

    With contributions from scientists at major institutions, this book presents an introduction to brain anatomy for engineers and scientists. It provides, for the first time, a comprehensive resource in the field of brain biomechanics.

  16. Brain Basics: Understanding Sleep

    Science.gov (United States)

    ... You are here Home » Disorders » Patient & Caregiver Education Brain Basics: Understanding Sleep Anatomy of Sleep Sleep Stages ... t form or maintain the pathways in your brain that let you learn and create new memories, ...

  17. Aneurysm in the brain

    Science.gov (United States)

    ... gov/ency/article/001414.htm Aneurysm in the brain To use the sharing features on this page, ... aneurysm occurs in a blood vessel of the brain, it is called a cerebral, or intracranial, aneurysm. ...

  18. Brain injury - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000163.htm Brain injury - discharge To use the sharing features on ... know was in the hospital for a serious brain injury. At home, it will take time for ...

  19. Genetic Brain Disorders

    Science.gov (United States)

    A genetic brain disorder is caused by a variation or a mutation in a gene. A variation is a different form ... mutation is a change in a gene. Genetic brain disorders affect the development and function of the ...

  20. Childhood Brain Tumors

    Science.gov (United States)

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  1. Brain aneurysm repair

    Science.gov (United States)

    ... aneurysm repair; Dissecting aneurysm repair; Endovascular aneurysm repair - brain; Subarachnoid hemorrhage - aneurysm ... Your scalp, skull, and the coverings of the brain are opened. A metal clip is placed at ...

  2. Children's Brain Tumor Foundation

    Science.gov (United States)

    ... 2 Family Donate Volunteer Justin's Hope Fund Children’s Brain Tumor Foundation, A non-profit organization, was founded ... and the long term outlook for children with brain and spinal cord tumors through research, support, education, ...

  3. Brain aneurysm repair - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000123.htm Brain aneurysm repair - discharge To use the sharing features ... this page, please enable JavaScript. You had a brain aneurysm . An aneurysm is a weak area in ...

  4. Numbers and brains.

    Science.gov (United States)

    Gallistel, C R

    2017-12-01

    The representation of discrete and continuous quantities appears to be ancient and pervasive in animal brains. Because numbers are the natural carriers of these representations, we may discover that in brains, it's numbers all the way down.

  5. Protect Your Brain

    Centers for Disease Control (CDC) Podcasts

    At least three and a half million people in the U.S. sustained a traumatic brain injury (TBI), either with or without other injuries. This podcast discusses the importance of early diagnosis and treatment of brain injuries.

  6. Traumatic Brain Injury

    Science.gov (United States)

    ... brain injury Some traumatic brain injuries have lasting effects, and some do not. You may be left with disabilities. These can be physical, behavioral, communicative, and/or mental. Customized treatment helps you to have as full ...

  7. Right Brain Drawing.

    Science.gov (United States)

    Whalen, Adryce C.

    1985-01-01

    The author describes activities of a weekly enrichment class providing right-brain tasks to gifted elementary students. Activities, which centered on artistic creativity, were taken from "Drawing On the Right Side of the Brain" by B. Edwards. (CL)

  8. Insulin and the Brain

    Directory of Open Access Journals (Sweden)

    Grosu Cristina

    2017-12-01

    Full Text Available The brain represents an important site for the action of insulin. Besides the traditionally known importance in glucoregulation, insulin has significant neurotrophic properties and influences the brain activity: insulin influences eating behavior, regulates the storage of energy and several aspects concerning memory and knowledge. Insulin resistance and hyperinsulinism could be associated with brain aging, vascular and metabolic pathologies. Elucidating the pathways and metabolism of brain insulin could have a major impact on future targeted therapies.

  9. Brain cancer spreads

    DEFF Research Database (Denmark)

    Perryman, Lara; Erler, Janine Terra

    2014-01-01

    The discovery that ~20% of patients with brain cancer have circulating tumor cells breaks the dogma that these cells are confined to the brain and has important clinical implications (Müller et al., this issue).......The discovery that ~20% of patients with brain cancer have circulating tumor cells breaks the dogma that these cells are confined to the brain and has important clinical implications (Müller et al., this issue)....

  10. Neuromythology of Einstein's brain.

    Science.gov (United States)

    Hines, Terence

    2014-07-01

    The idea that the brain of the great physicist Albert Einstein is different from "average" brains in both cellular structure and external shape is widespread. This belief is based on several studies examining Einstein's brain both histologically and morphologically. This paper reviews these studies and finds them wanting. Their results do not, in fact, provide support for the claim that the structure of Einstein's brain reflects his intellectual abilities. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Brain imaging and schizophrenia

    International Nuclear Information System (INIS)

    Martinot, J.L.; Dao-Castellana, M.H.

    1991-01-01

    Brain structures and brain function have been investigated by the new brain imaging techniques for more than ten years. In Psychiatry, these techniques could afford a new understanding of mental diseases. In schizophrenic patients, CAT scanner and RMI pointed out statistically significant ventricular enlargments which are presently considered as evidence for abnormalities in brain maturation. Functional imaging techniques reported metabolic dysfunctions in the cortical associative areas which are probably linked to the cognitive features of schizophrenics [fr

  12. Third International Congress on Epilepsy, Brain and Mind: Part 1

    Science.gov (United States)

    Korczyn, Amos D.; Schachter, Steven C.; Amlerova, Jana; Bialer, Meir; van Emde Boas, Walter; Brázdil, Milan; Brodtkorb, Eylert; Engel, Jerome; Gotman, Jean; Komárek, Vladmir; Leppik, Ilo E.; Marusic, Petr; Meletti, Stefano; Metternich, Birgitta; Moulin, Chris J.A.; Muhlert, Nils; Mula, Marco; Nakken, Karl O.; Picard, Fabienne; Schulze-Bonhage, Andreas; Theodore, William; Wolf, Peter; Zeman, Adam; Rektor, Ivan

    2017-01-01

    Epilepsyis both a disease of the brain and the mind. Here, we present the first of two papers with extended summaries of selected presentations of the Third International Congress on Epilepsy, Brain and Mind (April 3–5, 2014; Brno, Czech Republic). Epilepsy in history and the arts and its relationships with religion were discussed, as were overviews of epilepsy and relevant aspects of social cognition, handedness, accelerated forgetting and autobiographical amnesia, and large-scale brain networks. PMID:26276417

  13. Brain atrophy during aging

    International Nuclear Information System (INIS)

    Matsuzawa, Taiju; Takeda, Shumpei; Hatazawa, Jun

    1985-01-01

    Age-related brain atrophy was investigated in thousands of persons with no neurologic disturbances using X-CT and NMR-CT and following results were obtained. Brain atrophy was minimal in 34 -- 35 years old in both sexes, increased exponentially to the increasing age after 34 -- 35 years, and probably resulted in dementia, such as vascular or multiinfarct dementia. Brain atrophy was significantly greater in men than in women at all ages. Brain volumes were maximal in 34 -- 35 years old in both sexes with minimal individual differences which increased proportionally to the increasing age. Remarkable individual differences in the extents of brain atrophy (20 -- 30 %) existed among aged subjects. Some aged subjects had little or no atrophy of their brains, as seen in young subjects, and others had markedly shrunken brains associated with senility. From these results there must be pathological factors promoting brain atrophy with a great individual difference. We have studied the relation of intelligence to brain volume, and have ascertained that progression of brain atrophy was closely related to loss of mental activities independently of their ages. Our longitudinal study has revealed that the most important factors promoting brain atrophy during aging was decrease in the cerebral blood flow. MNR-CT can easily detected small infarction (lacunae) and edematous lesions resulting from ischemia and hypertensive encephalopathy, while X-CT can not. Therefore NMR-CT is very useful for detection of subtle changes in the brain. (J.P.N.)

  14. Brain Migration Revisited

    Science.gov (United States)

    Vinokur, Annie

    2006-01-01

    The "brain drain/brain gain" debate has been going on for the past 40 years, with irresolvable theoretical disputes and unenforceable policy recommendations that economists commonly ascribe to the lack of reliable empirical data. The recent report of the World Bank, "International migration, remittances and the brain drain", documents the…

  15. Radiopharmaceuticals for brain - SPECT

    International Nuclear Information System (INIS)

    Moretti, J.L.

    1992-01-01

    Perfusion tracers for brain SPECT imaging suitable for regional cerebral blood flow measurement and regional cerebral blood volume determination, with respect to their ability to pass the blood-brain-barrier, are described. Problems related t the use of specific radiotracers to map receptors distribution in the brain are also discussed in this lecture. 9 figs, 6 tabs

  16. Brain Research and Learning.

    Science.gov (United States)

    Claycomb, Mary

    Current research on brain activity has many implications for educators. The triune brain concept and the left and right hemisphere concepts are among the many complex theories evolving from experimentation and observation. The triune brain concept suggests that the human forebrain has expanded while retaining three structurally unique formations…

  17. Primary lymphoma of the brain

    Science.gov (United States)

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

  18. Hormones and the blood-brain barrier.

    Science.gov (United States)

    Hampl, Richard; Bičíková, Marie; Sosvorová, Lucie

    2015-03-01

    Hormones exert many actions in the brain, and brain cells are also hormonally active. To reach their targets in brain structures, hormones must overcome the blood-brain barrier (BBB). The BBB is a unique device selecting desired/undesired molecules to reach or leave the brain, and it is composed of endothelial cells forming the brain vasculature. These cells differ from other endothelial cells in their almost impermeable tight junctions and in possessing several membrane structures such as receptors, transporters, and metabolically active molecules, ensuring their selection function. The main ways how compounds pass through the BBB are briefly outlined in this review. The main part concerns the transport of major classes of hormones: steroids, including neurosteroids, thyroid hormones, insulin, and other peptide hormones regulating energy homeostasis, growth hormone, and also various cytokines. Peptide transporters mediating the saturable transport of individual classes of hormones are reviewed. The last paragraph provides examples of how hormones affect the permeability and function of the BBB either at the level of tight junctions or by various transporters.

  19. Brain water mapping with MR imaging

    International Nuclear Information System (INIS)

    Laine, F.J.; Fatouros, P.P.; Kraft, K.A.

    1990-01-01

    This paper reports on a recently developed MR imaging technique to determine the spatial distribution of brain water to healthy volunteers. A noninvasive MR imaging technique to obtain absolute measurements of brain water has been developed and validated with phantom and animal studies. Patient confirmation was obtained from independent gravimetric measurements of brain tissue samples harvested by biopsy. This approach entails the production of accurate T1 maps from multiple inversion recovery images of a selected anatomic section and their subsequent conversion into an absolute water image by means of a previously determined calibration curve. Twenty healthy volunteers were studied and their water distribution was determined in a standard section. The following brain water values means and SD grams of water per gram of tissue) were obtained for selected brain regions; white matter, 68.9% ± 1.0; corpus callosum, 67.4% ± 1.1; thalamus, 75.3% ± 1.4; and caudate nucleus, 80.3% ± 1.4. MR imaging water mapping is a valid means of determining water content in a variety of brain tissues

  20. Brain tumor and CT, 1

    International Nuclear Information System (INIS)

    Suzuki, Nobuyuki; Katada, Kazuhiro; Shinomiya, Youichi; Sano, Hirotoshi; Kanno, Tetsuo

    1981-01-01

    It is very important for a neurosurgeon to know the consistency of a brain tumor preoperatively, since the information which is of much use in indicating the likely difficulty of the operation, which operative tools should be selected, the amount of bleeding to be expected from the tumor, and so on. The authors, therefore, tried to evaluate the consistency of brain tumors preoperatively 27 cases in which the margin of the tumor was made clear with a homogeneous stain were studied concerning the relationship between the tumor consistency and the CT findings. The results are as follows: 1) A higher CT number on a plain CT indicated a harder consistency of the tumor. 2) A lesser contrast index (CT number on enhancement CT/CT number on plain CT) showed a harder consistency of the tumor. (author)

  1. Measurement of P-31 MR relaxation times and concentrations in human brain and brain tumors

    International Nuclear Information System (INIS)

    Roth, K.; Naruse, S.; Hubesch, B.; Gober, I.; Lawry, T.; Boska, M.; Matson, G.B.; Weiner, M.W.

    1987-01-01

    Measurements of high-energy phosphates and pH were made in human brain and brain tumors using P-31 MR imaging. Using a Philips Gyroscan 1.5-T MRMRS, MR images were used to select a cuboidal volume of interest and P-31 MR spectra were obtained from that volume using the ISIS technique. An external quantitation standard was used. T 1 s were measured by inversion recovery. Quantitative values for metabolites were calculated using B 1 field plot of the head coil. The results for normal brain phosphates are as follows; adenosine triphosphate, 2.2 mM; phosphocreatin, 5.3 mM; inorganic phosphate, 1.6 mM. Preliminary studies with human brain tumors show a decrease of all phosphate compounds. These experiments are the first to quantitate metabolites in human brain

  2. [Selective mutism].

    Science.gov (United States)

    Ytzhak, A; Doron, Y; Lahat, E; Livne, A

    2012-10-01

    Selective mutism is an uncommon disorder in young children, in which they selectively don't speak in certain social situations, while being capable of speaking easily in other social situations. Many etiologies were proposed for selective mutism including psychodynamic, behavioral and familial etc. A developmental etiology that includes insights from all the above is gaining support. Accordingly, mild language impairment in a child with an anxiety trait may be at the root of developing selective mutism. The behavior will be reinforced by an avoidant pattern in the family. Early treatment and followup for children with selective mutism is important. The treatment includes non-pharmacological therapy (psychodynamic, behavioral and familial) and pharmacologic therapy--mainly selective serotonin reuptake inhibitors (SSRI).

  3. Brain atrophy during aging

    International Nuclear Information System (INIS)

    Matsuzawa, Taiju; Yamada, Kenji; Yamada, Susumu; Ono, Shuichi; Takeda, Shunpei; Hatazawa, Jun; Ito, Masatoshi; Kubota, Kazuo

    1985-01-01

    Age-related brain atrophy was investigated in thousands of persons with no neurologic disturbances using X-CT and NMR-CT. Brain atrophy was minimal in 34-35 years old in both sexes, increased exponentially to the increasing age after 34-35 years, and probably resulted in dementia, such as vascular or multi-infarct dementia. Brain atrophy was significantly greater in men than in women at all ages. Brain volumes were maximal in 34-35 years old in both sexes with minimal individual differences which increased proportionally to the increasing age. Remarkable individual differences in the extent of brain atrophy (20 - 30 %) existed among aged subjects. Progression of brain atrophy was closely related to loss of mental activities independently of their ages. Our longitudinal study has revealed that the most important factors promoting brain atrophy during aging was the decrease in the cerebral blood flow. We have classified brain atrophy into sulcal and cisternal enlargement type (type I), ventricular enlargement type (type II) and mixed type (type III) according to the clinical study using NMR-CT. Brain atrophy of type I progresses significantly in almost all of the geriatric disorders. This type of brain atrophy progresses significantly in heavy smokers and drinkers. Therefore this type of brain atrophy might be caused by the decline in the blood flow in anterior and middle cerebral arteries. Brain atrophy of type II was caused by the disturbance of cerebrospinal fluid circulation after cerebral bleeding and subarachnoid bleeding. Brain atrophy of type III was seen in vascular dementia or multi-infarct dementia which was caused by loss of brain matter after multiple infarction, and was seen also in dementia of Alzheimer type in which degeneration of nerve cells results in brain atrophy. NMR-CT can easily detect small infarction (lacunae) and edematous lesions resulting from ischemia and hypertensive encephalopathy. (J.P.N.)

  4. Instant BrainShark

    CERN Document Server

    Li, Daniel

    2013-01-01

    Filled with practical, step-by-step instructions and clear explanations for the most important and useful tasks. ""Instant BrainShark"" is a step-by-step guide to creating online presentations using BrainShark. The book covers digital marketing best practices alongside tips for sales conversions. The book is written in an easy-to-read style for anybody to easily pick up and get started with BrainShark.Instant BrainShark is for anyone who wants to use BrainShark to create presentations online and share them around the community. The book is also useful for developers who are looking to explore

  5. David Ferrier: brain drawings and brain maps.

    Science.gov (United States)

    Lazar, J Wayne

    2013-01-01

    This chapter has two emphases, one is about the men who influenced the visual representations that David Ferrier (1843-1928) used to illustrate his work on localization of brain functions during the years 1873-1875, namely, Alexander Ecker, John C. Galton, and Ernest Waterlow, and the other is about the nature of medical representations and of Ferrier's illustrations in particular. Medical illustrations are characterized either as pictures, line drawings, or brain maps. Ferrier's illustrations will be shown to be increasingly sophisticated brain maps that contrast with early nineteenth-century standards of medical illustrations, as exemplified by John Bell (1763-1829). © 2013 Elsevier B.V. All rights reserved.

  6. Brain bank of the Brazilian aging brain study group - a milestone reached and more than 1,600 collected brains.

    Science.gov (United States)

    Grinberg, Lea Tenenholz; Ferretti, Renata Eloah de Lucena; Farfel, José Marcelo; Leite, Renata; Pasqualucci, Carlos Augusto; Rosemberg, Sérgio; Nitrini, Ricardo; Saldiva, Paulo Hilário Nascimento; Filho, Wilson Jacob

    2007-01-01

    Brain banking remains a necessity for the study of aging brain processes and related neurodegenerative diseases. In the present paper, we report the methods applied at and the first results of the Brain Bank of the Brazilian Aging Brain Study Group (BBBABSG) which has two main aims: (1) To collect a large number of brains of elderly comprising non-demented subjects and a large spectrum of pathologies related to aging brain processes, (2) To provide quality material to a multidisciplinar research network unraveling multiple aspects of aging brain processes and related neurodegenerative diseases. The subjects are selected from the Sao Paulo Autopsy Service. Brain parts are frozen and fixated. CSF, carotids, kidney, heart and blood are also collected and DNA is extracted. The neuropathological examinations are carried out based on accepted criteria, using immunohistochemistry. Functional status are assessed through a collateral source based on a clinical protocol. Protocols are approved by the local ethics committee and a written informed consent form is obtained. During the first 21 months, 1,602 samples were collected and were classified by Clinical Dementia Rating as CDR0: 65.7%; CDR0.5:12.6%, CDR1:8.2%, CDR2:5.4%, and CDR3:8.1%. On average, the cost for the processing each case stood at 400 US dollars. To date, 14 laboratories have been benefited by the BBBABSG. The high percentage of non- demented subjects and the ethnic diversity of this series may be significantly contributive toward aging brain processes and related neurodegenerative diseases understanding since BBBABSG outcomes may provide investigators the answers to some additional questions.

  7. Site selection

    CERN Multimedia

    CERN PhotoLab

    1968-01-01

    To help resolve the problem of site selection for the proposed 300 GeV machine, the Council selected "three wise men" (left to right, J H Bannier of the Netherlands, A Chavanne of Switzerland and L K Boggild of Denmark).

  8. Benchmark selection

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Tvede, Mich

    2002-01-01

    Within a production theoretic framework, this paper considers an axiomatic approach to benchmark selection. It is shown that two simple and weak axioms; efficiency and comprehensive monotonicity characterize a natural family of benchmarks which typically becomes unique. Further axioms are added...... in order to obtain a unique selection...

  9. Endothelial cell marker PAL-E reactivity in brain tumor, developing brain, and brain disease

    NARCIS (Netherlands)

    Leenstra, S.; Troost, D.; Das, P. K.; Claessen, N.; Becker, A. E.; Bosch, D. A.

    1993-01-01

    The endothelial cell marker PAL-E is not reactive to vessels in the normal brain. The present study concerns the PAL-E reactivity in brain tumors in contrast to normal brain and nonneoplastic brain disease. A total of 122 specimens were examined: brain tumors (n = 94), nonneoplastic brain disease (n

  10. 采用CT技术研究颅脑损伤患者的早期神经功能恢复:脑水肿和脑肿胀的比较%CT study of patients neurological function recovery in the acute stage of brain injury:compared brain swelling and brain edema

    Institute of Scientific and Technical Information of China (English)

    李龙; 池晓宇; 黄新才; 刘卫国; 蒋德清

    2002-01-01

    @@ ckground: Secondary clinical manifestations following brain injury may be due to either intracranial hemorrhage or brain edema and brain swelling.But brain swelling hasn't been understand adequately in clinical practice.Objective: 71 patients with brain edema or brain swelling following brain injury admitted to our hospital during Jan 1998 to Dec 1999 were selected for this study.Their CT findings were compared,and CT characters of traumatic brain swelling and neurological function recovery were analyzed emphatically.Unit: Department of Radiology,Guangdong Provincial Corps Hospital,Chinese People's Armed Police Forces.

  11. Mapping brain function to brain anatomy

    International Nuclear Information System (INIS)

    Valentino, D.J.; Huang, H.K.; Mazziotta, J.C.

    1988-01-01

    In Imaging the human brain, MRI is commonly used to reveal anatomical structure, while PET is used to reveal tissue function. This paper presents a protocol for correlating data between these two imaging modalities; this correlation can provide in vivo regional measurements of brain function which are essential to our understanding of the human brain. The authors propose a general protocol to standardize the acquisition and analysis of functional image data. First, MR and PET images are collected to form three-dimensional volumes of structural and functional image data. Second, these volumes of image data are corrected for distortions inherent in each imaging modality. Third, the image volumes are correlated to provide correctly aligned structural and functional images. The functional images are then mapped onto the structural images in both two-dimensional and three-dimensional representations. Finally, morphometric techniques can be used to provide statistical measures of the structure and function of the human brain

  12. Brain imaging during seizure: ictal brain SPECT

    International Nuclear Information System (INIS)

    Kottamasu, Sambasiva Rao

    1997-01-01

    The role of single photon computed tomography (SPECT) in presurgical localization of medically intractable complex partial epilepsy (CPE) in children is reviewed. 99m Technetium neurolite, a newer lipophylic agent with a high first pass brain extraction and little or no redistribution is injected during a seizure, while the child is monitored with a video recording and continuous EEG and SPECT imaging is performed in the next 1-3 hours with the images representing regional cerebral profusion at the time of injection. On SPECT studies performed with radiopharmaceutical injected during a seizure, ictal focus is generally hypervascular. Other findings on ictal brain SPECT include hypoperfusion of adjacent cerebral cortex and white matter, hyperperfusion of contralateral motor cortex, hyperperfusion of ipsilateral basal ganglia and thalamus, brain stem and contralateral cerebellum. Ictal brain SPECT is non-invasive, cost effective and highly sensitive for localization of epileptic focus in patients with intractable CPE. (author)

  13. Decompressive craniectomy following brain injury: factors important ...

    African Journals Online (AJOL)

    2010-01-07

    Jan 7, 2010 ... Background: Decompressive craniectomy (DC) is often performed as an empirical lifesaving measure to protect the injured brain from the damaging effects of propagating oedema and intracranial hypertension. However, there are no clearly defined indications or specified guidelines for patient selection for ...

  14. The selective alpha7 nicotinic acetylcholine receptor agonist PNU-282987 [N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride] enhances GABAergic synaptic activity in brain slices and restores auditory gating deficits in anesthetized rats.

    Science.gov (United States)

    Hajós, M; Hurst, R S; Hoffmann, W E; Krause, M; Wall, T M; Higdon, N R; Groppi, V E

    2005-03-01

    Schizophrenic patients are thought to have an impaired ability to process sensory information. This deficit leads to disrupted auditory gating measured electrophysiologically as a reduced suppression of the second of paired auditoryevoked responses (P50) and is proposed to be associated with decreased function and/or expression of the homomeric alpha7 nicotinic acetylcholine receptor (nAChR). Here, we provide evidence that N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-282987), a novel selective agonist of the alpha7 nAChR, evoked whole-cell currents from cultured rat hippocampal neurons that were sensitive to the selective alpha7 nAChR antagonist methyllycaconitine (MLA) and enhanced GABAergic synaptic activity when applied to hippocampal slices. Amphetamine-induced sensory gating deficit, determined by auditory-evoked potentials in hippocampal CA3 region, was restored by systemic administration of PNU-282987 in chloral hydrate-anesthetized rats. Auditory gating of rat reticular thalamic neurons was also disrupted by amphetamine; however, PNU-282987 normalized gating deficit only in a subset of tested neurons (6 of 11). Furthermore, PNU-282987 improved the inherent hippocampal gating deficit occurring in a subpopulation of anesthetized rats, and enhanced amphetamine-induced hippocampal oscillation. We propose that the alpha7 nAChR agonist PNU-282987, via modulating/enhancing hippocampal GABAergic neurotransmission, improves auditory gating and enhances hippocampal oscillatory activity. These results provide further support for the concept that drugs that selectively activate alpha7 nAChRs may offer a novel, potential pharmacotherapy in treatment of schizophrenia.

  15. Brain mechanisms of emotions.

    Science.gov (United States)

    Simonov, P V

    1997-01-01

    At the 23rd International Congress of Physiology Sciences (Tokyo, 1965) the results of experiment led us to the conclusion that emotions were determined by the actual need and estimation of probability (possibility) of its satisfaction. Low probability of need satisfaction leads to negative emotions actively minimized by the subject. Increased probability of satisfaction, as compared to the earlier forecast, generates positive emotions which the subject tries to maximize, that is, to enhance, to prolong, to repeat. We named our concept the Need-Informational Theory of Emotions. According to this theory, motivation, emotion, and estimation of probability have different neuromorphological substrates. Activation through the hypothalamic motivatiogenic structures of the frontal parts of the neocortex orients the behavior to signals with a high probability of their reinforcement. At the same time the hippocampus is necessary for reactions to signals of low probability events, which are typical for the emotionally excited brain. By comparison of motivational excitation with available stimuli or their engrams, the amygdala selects a dominant motivation, destined to be satisfied in the first instance. In the cases of classical conditioning and escape reaction the reinforcement was related to involvement of the negative emotion's hypothalamic neurons, while in the course of avoidance reaction the positive emotion's neurons were involved. The role of the left and right frontal neocortex in the appearance or positive or negative emotions depends on these informational (cognitive) functions.

  16. Selective mutism.

    Science.gov (United States)

    Hua, Alexandra; Major, Nili

    2016-02-01

    Selective mutism is a disorder in which an individual fails to speak in certain social situations though speaks normally in other settings. Most commonly, this disorder initially manifests when children fail to speak in school. Selective mutism results in significant social and academic impairment in those affected by it. This review will summarize the current understanding of selective mutism with regard to diagnosis, epidemiology, cause, prognosis, and treatment. Studies over the past 20 years have consistently demonstrated a strong relationship between selective mutism and anxiety, most notably social phobia. These findings have led to the recent reclassification of selective mutism as an anxiety disorder in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. In addition to anxiety, several other factors have been implicated in the development of selective mutism, including communication delays and immigration/bilingualism, adding to the complexity of the disorder. In the past few years, several randomized studies have supported the efficacy of psychosocial interventions based on a graduated exposure to situations requiring verbal communication. Less data are available regarding the use of pharmacologic treatment, though there are some studies that suggest a potential benefit. Selective mutism is a disorder that typically emerges in early childhood and is currently conceptualized as an anxiety disorder. The development of selective mutism appears to result from the interplay of a variety of genetic, temperamental, environmental, and developmental factors. Although little has been published about selective mutism in the general pediatric literature, pediatric clinicians are in a position to play an important role in the early diagnosis and treatment of this debilitating condition.

  17. A Microfabricated Transduction Coil for Inductive Deep Brain Stimulation

    Directory of Open Access Journals (Sweden)

    Jie (Jayne WU

    2006-07-01

    Full Text Available "Inductively Coupled Deep Brain Stimulator" describes a chip/system design to inductively couple arbitrary waveforms to electrodes embedded in the brain for deep brain stimulation or other neurostimulation. This approach moves the conventionally implanted signal generator outside the body and provides flexibility in adjusting waveforms to investigate optimum stimulation waveforms. An "inlaid electroplating" process with through-wafer plating is used to reduce microcoil resistance and integrate microstructures and electronics. Utilizing inductive link resonance specific to microcoils, waveforms are selectively transmitted to microcoils, which further produces biphasic waveforms that are suitable for deep brain stimulation.

  18. Lateralization of Egocentric and Allocentric Spatial Processing after Parietal Brain Lesions

    Science.gov (United States)

    Iachini, Tina; Ruggiero, Gennaro; Conson, Massimiliano; Trojano, Luigi

    2009-01-01

    The purpose of this paper was to verify whether left and right parietal brain lesions may selectively impair egocentric and allocentric processing of spatial information in near/far spaces. Two Right-Brain-Damaged (RBD), 2 Left-Brain-Damaged (LBD) patients (not affected by neglect or language disturbances) and eight normal controls were submitted…

  19. Presence of corticotrophin-releasing factor and/or tyrosine hydroxylase in cells of a neural brain-testicular pathway that are labelled by a transganglionic tracer.

    Science.gov (United States)

    James, P; Rivier, C; Lee, S

    2008-02-01

    Our laboratory has shown that male testosterone levels are not solely controlled by the release of hypothalamic gonadotrophin-releasing hormone and pituitary luteinising hormone, but are also regulated by a multisynaptic pathway connecting the brain and the testis that interferes with the testosterone response to gonadotrophins. This pathway, which is independent of the pituitary gland, is activated by an i.c.v. injection of either the stress-related peptide corticotrophin-releasing factor (CRF) or of beta-adrenoceptor agonists, both of which alter androgen release and decrease levels of the peripheral-type benzodiazepine receptor and the steroidogenic acute regulatory protein within Leydig cells. Our original studies used the retrograde transganglionic tracer pseudorabies virus (PRV) to map progression of the virus from the testes to upper brain levels. The present study aimed to extend this work by identifying the regions where CRF and catecholamine neurones represented components of the stress-activated, brain-testicular pathway that prevents testosterone increases. To this end, anaesthetised adult male rats received an intra-testicular injection of PRV. Using immunofluorescence, we identified co-labelling of PRV and either CRF or tyrosine hydroxylase (TH), the enzyme responsible for biogenic amine synthesis. Co-labelling of PRV and CRF was found in the bed nucleus of the stria terminalis, the paraventricular nucleus of the hypothalamus (PVN) and the central amygdala. Co-labelling of PRV and TH was found in the PVN, substantia nigra, A7/Kölliker-Fuse area, area of A5, locus coeruleus, nucleus of solitary tract, area of C3, area of C2 and the area of C1/A1. These results indicate that most cell groups of the ventral noradrenergic pathway have neurones that are a part of the brain-testicular pathway. This suggests that the stress hormones CRF and catecholamines may act as neurotransmitters that signal the pathway to inhibit increases in plasma testosterone levels.

  20. Handbook of Brain Connectivity

    CERN Document Server

    Jirsa, Viktor K

    2007-01-01

    Our contemporary understanding of brain function is deeply rooted in the ideas of the nonlinear dynamics of distributed networks. Cognition and motor coordination seem to arise from the interactions of local neuronal networks, which themselves are connected in large scales across the entire brain. The spatial architectures between various scales inevitably influence the dynamics of the brain and thereby its function. But how can we integrate brain connectivity amongst these structural and functional domains? Our Handbook provides an account of the current knowledge on the measurement, analysis and theory of the anatomical and functional connectivity of the brain. All contributors are leading experts in various fields concerning structural and functional brain connectivity. In the first part of the Handbook, the chapters focus on an introduction and discussion of the principles underlying connected neural systems. The second part introduces the currently available non-invasive technologies for measuring struct...

  1. Predator-driven brain size evolution in natural populations of Trinidadian killifish (Rivulus hartii)

    Science.gov (United States)

    Walsh, Matthew R.; Broyles, Whitnee; Beston, Shannon M.; Munch, Stephan B.

    2016-01-01

    Vertebrates exhibit extensive variation in relative brain size. It has long been assumed that this variation is the product of ecologically driven natural selection. Yet, despite more than 100 years of research, the ecological conditions that select for changes in brain size are unclear. Recent laboratory selection experiments showed that selection for larger brains is associated with increased survival in risky environments. Such results lead to the prediction that increased predation should favour increased brain size. Work on natural populations, however, foreshadows the opposite trajectory of evolution; increased predation favours increased boldness, slower learning, and may thereby select for a smaller brain. We tested the influence of predator-induced mortality on brain size evolution by quantifying brain size variation in a Trinidadian killifish, Rivulus hartii, from communities that differ in predation intensity. We observed strong genetic differences in male (but not female) brain size between fish communities; second generation laboratory-reared males from sites with predators exhibited smaller brains than Rivulus from sites in which they are the only fish present. Such trends oppose the results of recent laboratory selection experiments and are not explained by trade-offs with other components of fitness. Our results suggest that increased male brain size is favoured in less risky environments because of the fitness benefits associated with faster rates of learning and problem-solving behaviour. PMID:27412278

  2. Mapping the brain

    International Nuclear Information System (INIS)

    Begley, S.; Wright, L.; Church, V.; Hager, M.

    1992-01-01

    With powerful new technologies such as positron tomography and superconducting quantum interference device that peer through the skull and see the brain at work, neuroscientists seek the wellsprings of thoughts and emotions, the genesis of intelligence and language. A functional map of the brain is thus obtained and its challenge is to move beyond brain structure to create a detailed diagram of which part do what. For that the brain's cartographers rely on a variety of technologies such as positron tomography and superconducting quantum interference devices. Their performances and uses are briefly reviewed. ills

  3. Mild Traumatic Brain Injury

    Science.gov (United States)

    ... mild Traumatic Brain Injury Resilience Families with Kids Depression Families & Friendships Tobacco Life Stress Spirituality Anger Physical Injury Stigma Health & Wellness Work Adjustment Community Peer-2-Peer Forum ...

  4. Brain spect imaging

    International Nuclear Information System (INIS)

    Lee, R.G.L.; Hill, T.C.; Holman, B.L.

    1989-01-01

    This paper discusses how the rapid development of single-photon radiopharmaceuticals has given new life to tomographic brain imaging in nuclear medicine. Further developments in radiopharmaceuticals and refinements in neuro-SPECT (single-photon emission computed tomography) instrumentation should help to reinstate brain scintigraphy as an important part of neurologic diagnosis. SPECT of the brain evolved from experimentation using prototype instrumentation during the early 1960s. Although tomographic studies provided superior diagnostic accuracy when compared to planar techniques, the arrival of X-ray CT of the head resulted in the rapid demise of technetium brain imaging

  5. Species differences in [11C]clorgyline binding in brain

    International Nuclear Information System (INIS)

    Fowler, Joanna S.; Ding, Yu-Shin; Logan, Jean; MacGregor, Robert R.; Shea, Colleen; Garza, Victor; Gimi, Raomond; Volkow, Nora D.; Wang, Gene-Jack; Schlyer, David; Ferrieri, Richard; Gatley, S. John; Alexoff, David; Carter, Pauline; King, Payton; Pappas, Naomi; Arnett, Carroll D.

    2001-01-01

    [ 11 C]Clorgyline selectively binds to MAO A in the human brain. This contrasts with a recent report that [ 11 C]clorgyline (in contrast to other labeled MAO A inhibitors) is not retained in the rhesus monkey brain . To explore this difference, we compared [ 11 C]clorgyline in the baboon brain before and after clorgyline pretreatment and we also synthesized deuterium substituted [ 11 C]clorgyline (and its nor-precursor) for comparison. [ 11 C]Clorgyline was not retained in the baboon brain nor was it influenced by clorgyline pretreatment or by deuterium substitution, contrasting to results in humans. This suggests a species difference in the susceptibility of MAO A to inhibition by clorgyline and represents an unusual example of where the behavior of a radiotracer in the baboon brain does not predict its behavior in the human brain

  6. Changes of brain response induced by simulated weightlessness

    Science.gov (United States)

    Wei, Jinhe; Yan, Gongdong; Guan, Zhiqiang

    The characteristics change of brain response was studied during 15° head-down tilt (HDT) comparing with 45° head-up tilt (HUT). The brain responses evaluated included the EEG power spectra change at rest and during mental arithmetic, and the event-related potentials (ERPs) of somatosensory, selective attention and mental arithmetic activities. The prominent feature of brain response change during HDT revealed that the brain function was inhibited to some extent. Such inhibition included that the significant increment of "40Hz" activity during HUT arithmetic almost disappeared during HDT arithmetic, and that the positive-potential effect induced by HDT presented in all kinds of ERPs measured, but the slow negative wave reflecting mental arithmetic and memory process was elongated. These data suggest that the brain function be affected profoundly by the simulated weightlessness, therefore, the brain function change during space flight should be studied systematically.

  7. Music-reading deficiencies and the brain

    Directory of Open Access Journals (Sweden)

    Lola L. Cuddy

    2006-01-01

    Full Text Available This paper reviews the literature on brain damage and music-reading for the past 25 years. Acquired patterns of selective loss and sparing are described, including both the association and dissociation of music and text reading, and association and dissociation among components of music reading. As well, we suggest that developmental music - reading deficiencies may be isolated in a form analogous to developmental dyslexia for text or congenital amusia for auditory music processing. Finally, we propose that the results of brain damage studies can contribute to the development of a model of normal music reading.

  8. MRI of 'brain death'

    International Nuclear Information System (INIS)

    Nishino, Shigeki; Itoh, Takahiko; Tuchida, Shohei; Kinugasa, Kazushi; Asari, Shoji; Nishimoto, Akira; Sanou, Kazuo.

    1990-01-01

    Magnetic resonance imaging (MRI) was undertaken for two patients who suffered from severe cerebrovascular diseases and were clinically brain dead. The MRI system we used was Resona (Yokogawa Medical Systems, superconductive system 0.5 T) and the CT apparatus was Toshiba TCT-300. Initial CT and MRI were undertaken as soon as possible after admission, and repeated sequentially. After diagnosis of brain death, we performed angiography to determine cerebral circulatory arrest, and MRI obtained at the same time was compared with the angiogram and CT. Case 1 was a 77-year-old man who was admitted in an unconscious state. CT and MRI on the second day after hospitalization revealed cerebellar infarction. He was diagnosed as brain dead on day 4. Case 2 was a 35-year-old man. When he was transferred to our hospital, he was in cardiorespiratory arrested. Cardiac resuscitation was successful but no spontaneous respiration appeared. CT and MRI on admission revealed right intracerebral hemorrhage. Angiography revealed cessation of contrast medium in intracranial vessels in both of the patients. We found no 'flow signal void sign' in the bilateral internal carotid and basilar arteries on MRI images in both cases after brain death. MRI, showing us the anatomical changes of the brain, clearly revealed brain herniations, even though only nuclear findings of 'brain tamponade' were seen on CT. But in Case 1, we could not see the infarct lesions in the cerebellum on MR images obtained after brain death. This phenomenon was caused by the whole brain ischemia masking the initial ischemic lesions. We concluded that MRI was useful not only the anatomical display of lesions and brain herniation with high contrast resolution but for obtaining information on cerebral circulation of brain death. (author)

  9. Prolonged survival after resection and radiotherapy for solitary brain metastases from non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Chee, R. J.; Bydder, S.; Cameron, F.

    2007-01-01

    Selected patients with brain metastases from non-small-cell lung cancer benefit from aggressive treatment. This report describes three patients who developed solitary brain metastases after previous resection of primary adenocarcinoma of the lung. Each underwent surgical resection of their brain metastasis followed by cranial irradiation and remain disease free 10 or more years later. Two patients developed cognitive impairment approximately 8 years after treatment of their brain metastasis, which was felt to be due to their previous brain irradiation. Here we discuss the treatment of solitary brain metastasis, particularly the value of combined method approaches in selected patients and dose-volume considerations

  10. Expression and relevant research of MGMT and XRCC1 gene in differentgrades of brain glioma and normal brain tissues

    Institute of Scientific and Technical Information of China (English)

    Ya-Fei Zhang

    2015-01-01

    Objective: To explore and analyze expression and relevant research of MGMT and XRCC1 gene in different grades of brain glioma and normal brain tissues. Methods: 52 cases of patients with brain glioma treated in our hospital from December 2013 to December 2014, and 50 cases of normal brain-tissue patients with intracranial hypertension were selected, and proceeding test to the surgical resection of brain tissue of the above patients to determine its MGMT and XRCC1 protein content, sequentially to record the expression of MGMT and XRCC1 of both groups. Grading of tumors to brain glioma after operation was carried out, and the expression of MGMT and XRCC1 gene in brain tissues of different patients was analyzed and compared;finally the contingency tables of X2 test was used to analyze the correlation of XRCC1and MGMT. Results:Positive rate of MGMT expression in normal brain tissue was 2%,while positive rate of MGMT expression in brain glioma was 46.2%,which was obviously higher than that in normal brain tissues (χ2=26.85, P0.05), which had no statistical significance. There were 12 cases of patients whose MGMT protein expression was positive and XRCC1 protein expression was positive; there were 18 cases of patients whose MGMT protein expression was negative and XRCC1 protein expression was negative. Contingency tables of X2 test was used to analyze the correlation of XRCC1 and MGMT, which indicated that the expression of XRCCI and MGMT in brain glioma had no correlation (r=0.9%, P=0.353), relevancy of both was r=0.9%. Conclusions: Positive rate of the expression of MGMT and XRCC1 in brain glioma was obviously higher than that in normal brain tissues, but the distribution of different grades of brain glioma had no obvious difference, and MGMT and XRCC1 expression had no obvious correlation, which needed further research.

  11. Lipidomics of human brain aging and Alzheimer's disease pathology.

    Science.gov (United States)

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

  12. Do brain image databanks support understanding of normal ageing brain structure? A systematic review

    International Nuclear Information System (INIS)

    Dickie, David Alexander; Job, Dominic E.; Wardlaw, Joanna M.; Poole, Ian; Ahearn, Trevor S.; Staff, Roger T.; Murray, Alison D.

    2012-01-01

    To document accessible magnetic resonance (MR) brain images, metadata and statistical results from normal older subjects that may be used to improve diagnoses of dementia. We systematically reviewed published brain image databanks (print literature and Internet) concerned with normal ageing brain structure. From nine eligible databanks, there appeared to be 944 normal subjects aged ≥60 years. However, many subjects were in more than one databank and not all were fully representative of normal ageing clinical characteristics. Therefore, there were approximately 343 subjects aged ≥60 years with metadata representative of normal ageing, but only 98 subjects were openly accessible. No databank had the range of MR image sequences, e.g. T2*, fluid-attenuated inversion recovery (FLAIR), required to effectively characterise the features of brain ageing. No databank supported random subject retrieval; therefore, manual selection bias and errors may occur in studies that use these subjects as controls. Finally, no databank stored results from statistical analyses of its brain image and metadata that may be validated with analyses of further data. Brain image databanks require open access, more subjects, metadata, MR image sequences, searchability and statistical results to improve understanding of normal ageing brain structure and diagnoses of dementia. (orig.)

  13. Natural brain-information interfaces: Recommending information by relevance inferred from human brain signals

    Science.gov (United States)

    Eugster, Manuel J. A.; Ruotsalo, Tuukka; Spapé, Michiel M.; Barral, Oswald; Ravaja, Niklas; Jacucci, Giulio; Kaski, Samuel

    2016-01-01

    Finding relevant information from large document collections such as the World Wide Web is a common task in our daily lives. Estimation of a user’s interest or search intention is necessary to recommend and retrieve relevant information from these collections. We introduce a brain-information interface used for recommending information by relevance inferred directly from brain signals. In experiments, participants were asked to read Wikipedia documents about a selection of topics while their EEG was recorded. Based on the prediction of word relevance, the individual’s search intent was modeled and successfully used for retrieving new relevant documents from the whole English Wikipedia corpus. The results show that the users’ interests toward digital content can be modeled from the brain signals evoked by reading. The introduced brain-relevance paradigm enables the recommendation of information without any explicit user interaction and may be applied across diverse information-intensive applications. PMID:27929077

  14. Overexpression of the steroidogenic enzyme cytochrome P450 side chain cleavage in the ventral tegmental area increases 3α,5α-THP and reduces long-term operant ethanol self-administration.

    Science.gov (United States)

    Cook, Jason B; Werner, David F; Maldonado-Devincci, Antoniette M; Leonard, Maggie N; Fisher, Kristen R; O'Buckley, Todd K; Porcu, Patrizia; McCown, Thomas J; Besheer, Joyce; Hodge, Clyde W; Morrow, A Leslie

    2014-04-23

    Neuroactive steroids are endogenous neuromodulators capable of altering neuronal activity and behavior. In rodents, systemic administration of endogenous or synthetic neuroactive steroids reduces ethanol self-administration. We hypothesized this effect arises from actions within mesolimbic brain regions that we targeted by viral gene delivery. Cytochrome P450 side chain cleavage (P450scc) converts cholesterol to pregnenolone, the rate-limiting enzymatic reaction in neurosteroidogenesis. Therefore, we constructed a recombinant adeno-associated serotype 2 viral vector (rAAV2), which drives P450scc expression and neuroactive steroid synthesis. The P450scc-expressing vector (rAAV2-P450scc) or control GFP-expressing vector (rAAV2-GFP) were injected bilaterally into the ventral tegmental area (VTA) or nucleus accumbens (NAc) of alcohol preferring (P) rats trained to self-administer ethanol. P450scc overexpression in the VTA significantly reduced ethanol self-administration by 20% over the 3 week test period. P450scc overexpression in the NAc, however, did not alter ethanol self-administration. Locomotor activity was unaltered by vector administration to either region. P450scc overexpression produced a 36% increase in (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone)-positive cells in the VTA, but did not increase 3α,5α-THP immunoreactivity in NAc. These results suggest that P450scc overexpression and the resultant increase of 3α,5α-THP-positive cells in the VTA reduces ethanol reinforcement. 3α,5α-THP is localized to neurons in the VTA, including tyrosine hydroxylase neurons, but not astrocytes. Overall, the results demonstrate that using gene delivery to modulate neuroactive steroids shows promise for examining the neuronal mechanisms of moderate ethanol drinking, which could be extended to other behavioral paradigms and neuropsychiatric pathology.

  15. The multilingual brain

    OpenAIRE

    Engel de Abreu, Pascale

    2013-01-01

    The multilingual brain. Is a multilingual education beneficial for children? What are the optimal conditions under which a child can become perfectly multilingual? The given lecture will focus on the "cognitive advantages" of multilingualism and illustrate the impact that being multilingual has on the cognitive organisation of the brain. Practical questions regarding multilingual education will also be discussed.

  16. The Resilient Brain

    Science.gov (United States)

    Brendtro, Larry K.; Longhurst, James E.

    2005-01-01

    Brain research opens new frontiers in working with children and youth experiencing conflict in school and community. Blending this knowledge with resilience science offers a roadmap for reclaiming those identified as "at risk." This article applies findings from resilience research and recent brain research to identify strategies for reaching…

  17. Brain PET scan

    Science.gov (United States)

    ... results on a PET scan. Blood sugar or insulin levels may affect the test results in people with diabetes . PET scans may be done along with a CT scan. This combination scan is called a PET/CT. Alternative Names Brain positron emission tomography; PET scan - brain References Chernecky ...

  18. What a Brain!

    Science.gov (United States)

    Love, Kim

    1997-01-01

    Outlines basic concepts about how the brain develops and considers how Head Start teachers and parents can take full advantage of the brain's multisensory learning approach to develop more effective ways to interact with children. Focuses on the critical developmental period for stimulating neurons and developing neural connections. Suggests…

  19. Baby brain atlases.

    Science.gov (United States)

    Oishi, Kenichi; Chang, Linda; Huang, Hao

    2018-04-03

    The baby brain is constantly changing due to its active neurodevelopment, and research into the baby brain is one of the frontiers in neuroscience. To help guide neuroscientists and clinicians in their investigation of this frontier, maps of the baby brain, which contain a priori knowledge about neurodevelopment and anatomy, are essential. "Brain atlas" in this review refers to a 3D-brain image with a set of reference labels, such as a parcellation map, as the anatomical reference that guides the mapping of the brain. Recent advancements in scanners, sequences, and motion control methodologies enable the creation of various types of high-resolution baby brain atlases. What is becoming clear is that one atlas is not sufficient to characterize the existing knowledge about the anatomical variations, disease-related anatomical alterations, and the variations in time-dependent changes. In this review, the types and roles of the human baby brain MRI atlases that are currently available are described and discussed, and future directions in the field of developmental neuroscience and its clinical applications are proposed. The potential use of disease-based atlases to characterize clinically relevant information, such as clinical labels, in addition to conventional anatomical labels, is also discussed. Copyright © 2018. Published by Elsevier Inc.

  20. Migraine and brain changes

    NARCIS (Netherlands)

    Meinders, I.H.

    2018-01-01

    This thesis describes the longitudinal population-based CAMERA-study on the association between migraine and brain changes (e.g. white matter hyperintensities, infarct-like and other lesions) and possible causes and consequences of those brain changes. Women with migraine showed higher incidence of

  1. Brain imaging in psychiatry

    International Nuclear Information System (INIS)

    Morihisa, J.M.

    1984-01-01

    This book contains the following five chapters: Positron Emission Tomography (PET) in Psychiatry; Regional Cerebral Blood Flow (CBF) in Psychiatry: Methodological Issues; Regional Cerebral Blood Flow in Psychiatry: Application to Clinical Research; Regional Cerebral Blood Flow in Psychiatry: The Resting and Activated Brains of Schizophrenic Patients; and Brain Electrical Activity Mapping (BEAM) in Psychiatry

  2. Inside the Adolescent Brain

    Science.gov (United States)

    Drury, Stacy S.

    2009-01-01

    Dr. Jay Giedd says that the main alterations in the adolescent brain are the inverted U-shaped developmental trajectories with late childhood/early teen peaks for gray matter volume among others. Giedd adds that the adolescent brain is vulnerable to substances that artificially modulate dopamine levels since its reward system is in a state of flux.

  3. One brain, two selves

    NARCIS (Netherlands)

    Reinders, AATS; Nijenhuis, ERS; Paans, AMJ; Korf, J; Willemsen, ATM; den Boer, JA

    2003-01-01

    Having a sense of self is an explicit and high-level functional specialization of the human brain. The anatomical localization of self-awareness and the brain mechanisms involved in consciousness were investigated by functional neuroimaging different emotional mental states of core consciousness in

  4. Coping changes the brain

    Directory of Open Access Journals (Sweden)

    Jordan M. Nechvatal

    2013-02-01

    Full Text Available One of the earliest and most consistent findings in behavioral neuroscience research is that learning changes the brain. Here we consider how learning as an aspect of coping in the context of stress exposure induces neuroadaptations that enhance emotion regulation and resilience. A systematic review of the literature identified 15 brain imaging studies in which humans with specific phobias or posttraumatic stress disorder were randomized to stress exposure therapies that diminished subsequent indications of anxiety. Most of these studies focused on functional changes in the amygdala and anterior corticolimbic brain circuits that control cognitive, motivational, and emotional aspects of physiology and behavior. Corresponding structural brain changes and the timing, frequency, and duration of stress exposure required to modify brain functions remain to be elucidated in future research. These studies will advance our understanding of coping as a learning process and provide mechanistic insights for the development of new interventions that promote stress coping skills.

  5. Epilepsy and Brain Tumors

    Institute of Scientific and Technical Information of China (English)

    Zhi-yi Sha

    2009-01-01

    @@ Epidemiology It is estimated 61,414 new cases of primary brain tumors are expected to be diagnosed in 2009 in the U.S. The incidence statistic of 61,414 persons diagnosed per year includes both malignant (22,738) and non-malignant (38,677) brain tumors. (Data from American Brain Tumor Association). During the years 2004-2005, approximately 359,000 people in the United States were living with the diagnosis of a primary brain or central nervous system tumor. Specifically, more than 81,000 persons were living with a malignant tumor, more than 267,000 persons with a benign tumor. For every 100,000 people in the United States, approximately 131 are living following the diagnosis of a brain tumor. This represents a prevalence rate of 130.8 per 100,000 person years[1].

  6. Brain-computer interfaces

    DEFF Research Database (Denmark)

    Treder, Matthias S.; Miklody, Daniel; Blankertz, Benjamin

    quality measure'. We were able to show that for stimuli close to the perceptual threshold, there was sometimes a discrepancy between overt responses and brain responses, shedding light on subjects using different response criteria (e.g., more liberal or more conservative). To conclude, brain-computer...... of perceptual and cognitive biases. Furthermore, subjects can only report on stimuli if they have a clear percept of them. On the other hand, the electroencephalogram (EEG), the electrical brain activity measured with electrodes on the scalp, is a more direct measure. It allows us to tap into the ongoing neural...... auditory processing stream. In particular, it can tap brain processes that are pre-conscious or even unconscious, such as the earliest brain responses to sounds stimuli in primary auditory cortex. In a series of studies, we used a machine learning approach to show that the EEG can accurately reflect...

  7. Inside the Diabetic Brain

    Directory of Open Access Journals (Sweden)

    Chomova M.

    2014-12-01

    Full Text Available CNS complications resulting from diabetes mellitus (DM are a problem gaining more acceptance and attention in the recent years. Both types 1 and 2 DM represent an significant risk factor for decreased cognitive functions, memory and learning deficits as well as development of Alzheimer’s disease. Chronic hyperglycemia through protein glycation and increased oxidative stress contributes to brain dysfunction, however increasing evidences suggest that the pathology of DM in the brain involves a progressive and coordinated disruption of insulin signaling, with profound consequences for brain function and plasticity. Since many of the CNS changes observed in diabetic patients and animal models of DM are reminiscent of the changes seen in aging, the theory of advanced brain aging in DM has been proposed. This review summarizes the findings of the literature regarding the effects of DM on the brain in the terms of diabetes-related metabolic derangements and intracellular signaling.

  8. Modeling Structural Brain Connectivity

    DEFF Research Database (Denmark)

    Ambrosen, Karen Marie Sandø

    The human brain consists of a gigantic complex network of interconnected neurons. Together all these connections determine who we are, how we react and how we interpret the world. Knowledge about how the brain is connected can further our understanding of the brain’s structural organization, help...... improve diagnosis, and potentially allow better treatment of a wide range of neurological disorders. Tractography based on diffusion magnetic resonance imaging is a unique tool to estimate this “structural connectivity” of the brain non-invasively and in vivo. During the last decade, brain connectivity...... has increasingly been analyzed using graph theoretic measures adopted from network science and this characterization of the brain’s structural connectivity has been shown to be useful for the classification of populations, such as healthy and diseased subjects. The structural connectivity of the brain...

  9. Exploring the brain

    International Nuclear Information System (INIS)

    Bloch, G.; Vernier, P.; Le Bihan, D.; Comtat, C.; Van Wassenhove, V.; Texier, I.; Planat-Chretien, A.; Poher, V.; Dinten, J.M.; Pannetier-lecoeur, M.; Trebossen, R.; Lethimonnier, F.; Eger, E.; Thirion, B.; Dehaene-Lambertz, G.; Piazza, M.; Mangin, J.F.; Dehaene, S.; Pallier, C.; Marti, S.; Klein, E.; Martinot, J.L.; Paillere, M.L.; Artiges, E.; Lemaitre, H.; Karila, L.; Houenou, J.; Sarrazin, S.; Hantraye, P.; Aron Badin, R.; Mergui, S.; Palfi, S.; Bemelmans, A.; Berger, F.; Frouin, V.; Pinel, J.F.; Crivello, F.; Mazoyer, B.; Flury-Herard, A.

    2014-01-01

    CEA (French Alternative Energies and Atomic Energy Commission) has been involved in brain research for over 50 years and this 62. issue of 'Clefs CEA' is the best occasion to come back on the latest advances in this wide field. The purpose is to show how neuroimaging combined with neuro sciences and computational sciences has shed light on various aspects of the brain life and experience such as for instance learning (with highlights on dyslexia and dyscalculia), vision, the feeling of time, consciousness, addictions, ageing, and neuro-degenerative diseases. This document is divided into 6 parts: 1) non-invasive exploration of the brain, 2) development, learning and plasticity of the brain, 3) cognitive architecture and the brain, 4) mental health and vulnerability, 5) neuro-degenerative diseases, and 6) identifying bio-markers for cerebral disorders. (A.C.)

  10. Selective oxidation

    International Nuclear Information System (INIS)

    Cortes Henao, Luis F.; Castro F, Carlos A.

    2000-01-01

    It is presented a revision and discussion about the characteristics and factors that relate activity and selectivity in the catalytic and not catalytic partial oxidation of methane and the effect of variables as the temperature, pressure and others in the methane conversion to methanol. It thinks about the zeolites use modified for the catalytic oxidation of natural gas

  11. Selective gossip

    NARCIS (Netherlands)

    Üstebay, D.; Castro, R.M.; Rabbat, M.

    2009-01-01

    Motivated by applications in compression and distributed transform coding, we propose a new gossip algorithm called Selective Gossip to efficiently compute sparse approximations of network data. We consider running parallel gossip algorithms on the elements of a vector of transform coefficients.

  12. Brain Aneurysm Statistics and Facts

    Science.gov (United States)

    ... Statistics and Facts A- A A+ Brain Aneurysm Statistics and Facts An estimated 6 million people in ... Understanding the Brain Warning Signs/ Symptoms Brain Aneurysm Statistics and Facts Seeking Medical Attention Risk Factors Aneurysm ...

  13. Plumbing the brain drain.

    Science.gov (United States)

    Saravia, Nancy Gore; Miranda, Juan Francisco

    2004-08-01

    Opportunity is the driving force of migration. Unsatisfied demands for higher education and skills, which have been created by the knowledge-based global economy, have generated unprecedented opportunities in knowledge-intensive service industries. These multi-trillion dollar industries include information, communication, finance, business, education and health. The leading industrialized nations are also the focal points of knowledge-intensive service industries and as such constitute centres of research and development activity that proactively draw in talented individuals worldwide through selective immigration policies, employment opportunities and targeted recruitment. Higher education is another major conduit of talent from less-developed countries to the centres of the knowledge-based global economy. Together career and educational opportunities drive "brain drain and recirculation". The departure of a large proportion of the most competent and innovative individuals from developing nations slows the achievement of the critical mass needed to generate the enabling context in which knowledge creation occurs. To favourably modify the asymmetric movement and distribution of global talent, developing countries must implement bold and creative strategies that are backed by national policies to: provide world-class educational opportunities, construct knowledge-based research and development industries, and sustainably finance the required investment for these strategies. Brazil, China and India have moved in this direction, offering world-class education in areas crucial to national development, such as biotechnology and information technology, paralleled by investments in research and development. As a result, only a small proportion of the most highly educated individuals migrate from these countries, and research and development opportunities employ national talent and even attract immigrants.

  14. The negative brain scintiscan in brain tumours

    International Nuclear Information System (INIS)

    Dalke, K.G.

    1978-01-01

    On the basis of 53 histologically verified and two histologically unidentified brain tumours, the author examined the reasons for these wrongly negative scintiscans. EEGs and angiographies carried out at about the same time were taken into account and compared with the scintigraphic findings. (orig.) [de

  15. Me, myself my brain implant : deep brain stimulation raises quistions of personal authenticity and alienation

    NARCIS (Netherlands)

    Kraemer, U.A.F.

    2013-01-01

    In this article, I explore select case studies of Parkinson patients treated with deep brain stimulation (DBS) in light of the notions of alienation and authenticity. While the literature on DBS has so far neglected the issues of authenticity and alienation, I argue that interpreting these cases in

  16. Brain Transcriptional and Epigenetic Associations with Autism

    Science.gov (United States)

    Ginsberg, Matthew R.; Rubin, Robert A.; Falcone, Tatiana; Ting, Angela H.; Natowicz, Marvin R.

    2012-01-01

    Background Autism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic. Methodology/Principal Findings To uncover important gene dysregulation in autism we analyzed carefully selected idiopathic autistic and control cerebellar and BA19 (occipital) brain tissues using high resolution whole genome gene expression and whole genome DNA methylation microarrays. No changes in DNA methylation were identified in autistic brain but gene expression abnormalities in two areas of metabolism were apparent: down-regulation of genes of mitochondrial oxidative phosphorylation and of protein translation. We also found associations between specific behavioral domains of autism and specific brain gene expression modules related to myelin/myelination, inflammation/immune response and purinergic signaling. Conclusions/Significance This work highlights two largely unrecognized molecular pathophysiological themes in autism and suggests differing molecular bases for autism behavioral endophenotypes. PMID:22984548

  17. Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats.

    Science.gov (United States)

    McBride, Devin W; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H

    2015-09-01

    Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected to either sham surgery or surgical brain injury via partial frontal lobectomy. All animals were tested for neurological deficits 24 post-SBI and fourteen were also tested 72 h after surgery using seven common behavior tests: modified Garcia neuroscore (Neuroscore), beam walking, corner turn test, forelimb placement test, adhesive removal test, beam balance test, and foot fault test. After assessing the functional outcome, animals were euthanized for brain water content measurement. Surgical brain injury resulted in significantly elevated frontal lobe brain water content 24 and 72 h after surgery compared to that of sham animals. In all behavior tests, significance was observed between sham and SBI animals. However, a correlation between brain water content and functional outcome was observed for all tests except Neuroscore. The selection of behavior tests is critical to determine the effectiveness of therapeutics. Based on this study's results, we recommend using beam walking, the corner turn test, the beam balance test, and the foot fault test since correlations with brain water content were observed at both 24 and 72 h post-SBI. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats

    Science.gov (United States)

    McBride, Devin W.; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H.

    2015-01-01

    Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected to either sham surgery or surgical brain injury via partial frontal lobectomy. All animals were tested for neurological deficits 24 post-SBI and fourteen were also tested 72 hours after surgery using seven common behavior tests: modified Garcia neuroscore (Neuroscore), beam walking, corner turn test, forelimb placement test, adhesive removal test, beam balance test, and foot fault test. After assessing the functional outcome, animals were euthanized for brain water content measurement. Surgical brain injury resulted in a significantly elevated frontal lobe brain water content 24 and 72 hours after surgery compared to that of sham animals. In all behavior tests, significance was observed between sham and SBI animals. However, a correlation between brain water content and functional outcome was observed for all tests except Neuroscore. The selection of behavior tests is critical to determine the effectiveness of therapeutics. Based on this study’s results, we recommend using beam walking, the corner turn test, the beam balance test, and the foot fault test since correlations with brain water content were observed at both 24 and 72 hours post-SBI. PMID:25975171

  19. Ricardian selection

    OpenAIRE

    Finicelli, Andrea; Pagano, Patrizio; Sbracia, Massimo

    2009-01-01

    We analyze the foundations of the relationship between trade and total factor productivity (TFP) in the Ricardian model. Under general assumptions about the autarky distributions of industry productivities, trade openness raises TFP. This is due to the selection effect of international competition � driven by comparative advantages � which makes "some" high- and "many" low-productivity industries exit the market. We derive a model-based measure of this effect that requires only production...

  20. Lutein and Brain Function

    Directory of Open Access Journals (Sweden)

    John W. Erdman

    2015-10-01

    Full Text Available Lutein is one of the most prevalent carotenoids in nature and in the human diet. Together with zeaxanthin, it is highly concentrated as macular pigment in the foveal retina of primates, attenuating blue light exposure, providing protection from photo-oxidation and enhancing visual performance. Recently, interest in lutein has expanded beyond the retina to its possible contributions to brain development and function. Only primates accumulate lutein within the brain, but little is known about its distribution or physiological role. Our team has begun to utilize the rhesus macaque (Macaca mulatta model to study the uptake and bio-localization of lutein in the brain. Our overall goal has been to assess the association of lutein localization with brain function. In this review, we will first cover the evolution of the non-human primate model for lutein and brain studies, discuss prior association studies of lutein with retina and brain function, and review approaches that can be used to localize brain lutein. We also describe our approach to the biosynthesis of 13C-lutein, which will allow investigation of lutein flux, localization, metabolism and pharmacokinetics. Lastly, we describe potential future research opportunities.

  1. Cannabinoids on the Brain

    Directory of Open Access Journals (Sweden)

    Andrew J. Irving

    2002-01-01

    Full Text Available Cannabis has a long history of consumption both for recreational and medicinal uses. Recently there have been significant advances in our understanding of how cannabis and related compounds (cannabinoids affect the brain and this review addresses the current state of knowledge of these effects. Cannabinoids act primarily via two types of receptor, CB1 and CB2, with CB1 receptors mediating most of the central actions of cannabinoids. The presence of a new type of brain cannabinoid receptor is also indicated. Important advances have been made in our understanding of cannabinoid receptor signaling pathways, their modulation of synaptic transmission and plasticity, the cellular targets of cannabinoids in different central nervous system (CNS regions and, in particular, the role of the endogenous brain cannabinoid (endocannabinoid system. Cannabinoids have widespread actions in the brain: in the hippocampus they influence learning and memory; in the basal ganglia they modulate locomotor activity and reward pathways; in the hypothalamus they have a role in the control of appetite. Cannabinoids may also be protective against neurodegeneration and brain damage and exhibit anticonvulsant activity. Some of the analgesic effects of cannabinoids also appear to involve sites within the brain. These advances in our understanding of the actions of cannabinoids and the brain endocannabinoid system have led to important new insights into neuronal function which are likely to result in the development of new therapeutic strategies for the treatment of a number of key CNS disorders.

  2. Human brain imaging

    International Nuclear Information System (INIS)

    Kuhar, M.J.

    1987-01-01

    Just as there have been dramatic advances in the molecular biology of the human brain in recent years, there also have been remarkable advances in brain imaging. This paper reports on the development and broad application of microscopic imaging techniques which include the autoradiographic localization of receptors and the measurement of glucose utilization by autoradiography. These approaches provide great sensitivity and excellent anatomical resolution in exploring brain organization and function. The first noninvasive external imaging of receptor distributions in the living human brain was achieved by positron emission tomography (PET) scanning. Developments, techniques and applications continue to progress. Magnetic resonance imaging (MRI) is also becoming important. Its initial clinical applications were in examining the structure and anatomy of the brain. However, more recent uses, such as MRI spectroscopy, indicate the feasibility of exploring biochemical pathways in the brain, the metabolism of drugs in the brain, and also of examining some of these procedures at an anatomical resolution which is substantially greater than that obtainable by PET scanning. The issues will be discussed in greater detail

  3. Abnormal rich club organization and functional brain dynamics in schizophrenia.

    Science.gov (United States)

    van den Heuvel, Martijn P; Sporns, Olaf; Collin, Guusje; Scheewe, Thomas; Mandl, René C W; Cahn, Wiepke; Goñi, Joaquín; Hulshoff Pol, Hilleke E; Kahn, René S

    2013-08-01

    The human brain forms a large-scale structural network of regions and interregional pathways. Recent studies have reported the existence of a selective set of highly central and interconnected hub regions that may play a crucial role in the brain's integrative processes, together forming a central backbone for global brain communication. Abnormal brain connectivity may have a key role in the pathophysiology of schizophrenia. To examine the structure of the rich club in schizophrenia and its role in global functional brain dynamics. Structural diffusion tensor imaging and resting-state functional magnetic resonance imaging were performed in patients with schizophrenia and matched healthy controls. Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands. Forty-eight patients and 45 healthy controls participated in the study. An independent replication data set of 41 patients and 51 healthy controls was included to replicate and validate significant findings. MAIN OUTCOME(S) AND MEASURES: Measures of rich club organization, connectivity density of rich club connections and connections linking peripheral regions to brain hubs, measures of global brain network efficiency, and measures of coupling between brain structure and functional dynamics. Rich club organization between high-degree hub nodes was significantly affected in patients, together with a reduced density of rich club connections predominantly comprising the white matter pathways that link the midline frontal, parietal, and insular hub regions. This reduction in rich club density was found to be associated with lower levels of global communication capacity, a relationship that was absent for other white matter pathways. In addition, patients had an increase in the strength of structural connectivity-functional connectivity coupling. Our findings provide novel biological evidence that schizophrenia is characterized by a selective

  4. Usefulness of brain SPECT

    International Nuclear Information System (INIS)

    Raynaud, C.; Rancurel, G.; Kieffer, E.; Ricard, S.; Askienazy, S.; Moretti, J.L.; Bourdoiseau, M.; Rapin, J.; Soussaline, F.

    1983-01-01

    Brain SPECT was not effectively exploited until I-123 isopropyl amphetamine (IAMP), indicator able to penetrate the blood brain barrier, became available. Although the experience of research teams working with IAMP is quite restricted due to the high cost of the indicator, some applications now appear to be worth the cost and in some cases provide data which cannot be obtained with routine techniques, especially in cerebrovascular patients, in epilepsy and some cases of tumor. Brain SPECT appears as an atraumatic test which is useful to establish a functional evaluation of the cerebral parenchyma, and which is a complement to arteriography, X-ray scan and regional cerebral blood flow measurement

  5. Brain Drain: A Child's Brain on Poverty. Poverty Fact Sheet

    Science.gov (United States)

    Damron, Neil

    2015-01-01

    "Brain Drain: A Child's Brain on Poverty," released in March 2015 and prepared by intern Neil Damron, explores the brain's basic anatomy and recent research findings suggesting that poverty affects the brain development of infants and young children and the potential lifelong effects of the changes. The sheet draws from a variety of…

  6. A Right Brain/Left Brain Model of Acting.

    Science.gov (United States)

    Bowlen, Clark

    Using current right brain/left brain research, this paper develops a model that explains acting's underlying quality--the actor is both himself and the character. Part 1 presents (1) the background of the right brain/left brain theory, (2) studies showing that propositional communication is a left hemisphere function while affective communication…

  7. Silent communication: toward using brain signals.

    Science.gov (United States)

    Pei, Xiaomei; Hill, Jeremy; Schalk, Gerwin

    2012-01-01

    From the 1980s movie Firefox to the more recent Avatar, popular science fiction has speculated about the possibility of a persons thoughts being read directly from his or her brain. Such braincomputer interfaces (BCIs) might allow people who are paralyzed to communicate with and control their environment, and there might also be applications in military situations wherever silent user-to-user communication is desirable. Previous studies have shown that BCI systems can use brain signals related to movements and movement imagery or attention-based character selection. Although these systems have successfully demonstrated the possibility to control devices using brain function, directly inferring which word a person intends to communicate has been elusive. A BCI using imagined speech might provide such a practical, intuitive device. Toward this goal, our studies to date addressed two scientific questions: (1) Can brain signals accurately characterize different aspects of speech? (2) Is it possible to predict spoken or imagined words or their components using brain signals?

  8. Cost of disorders of the brain in Denmark

    DEFF Research Database (Denmark)

    Olesen, J.; Sobocki, P.; Truelsen, T.

    2008-01-01

    The cost of brain disorders in Denmark is unknown and such information is important to decision makers. The aims of the study were to estimate the total number of subjects with brain diseases, and the associated direct and indirect expenses in Denmark. This was part of a larger pan-European study...... drug consumption was used for treatment of brain diseases. Expenses to brain diseases constituted 3% of the gross domestic product. Brain disorders are very prevalent in Denmark and they cause high societal and personal cost Udgivelsesdato: 2008......The cost of brain disorders in Denmark is unknown and such information is important to decision makers. The aims of the study were to estimate the total number of subjects with brain diseases, and the associated direct and indirect expenses in Denmark. This was part of a larger pan-European study......,000 and 340,000 patients, respectively. The total expenses for all selected brain diseases were 37.3 billion DKR. Affective disorders, dependency, dementia and stroke were the most costly diseases. An estimated 12% of all direct costs in the Danish health system were spent on brain diseases; 9% of the total...

  9. Selective Europeanization

    DEFF Research Database (Denmark)

    Hoch Jovanovic, Tamara; Lynggaard, Kennet

    2014-01-01

    and rules. The article examines the reasons for both resistance and selectiveness to Europeanization of the Danish minority policy through a “path dependency” perspective accentuating decision makers’ reluctance to deviate from existing institutional commitments, even in subsequently significantly altered...... political contexts at the European level. We further show how the “translation” of international norms to a domestic context has worked to reinforce the original institutional setup, dating back to the mid-1950s. The translation of European-level minority policy developed in the 1990s and 2000s works most...

  10. Selective Reproduction

    DEFF Research Database (Denmark)

    Svendsen, Mette N.

    2015-01-01

    This article employs a multi-species perspective in investigating how life's worth is negotiated in the field of neonatology in Denmark. It does so by comparing decision-making processes about human infants in the Danish neonatal intensive care unit with those associated with piglets who serve as...... as expectations within linear or predictive time frames are key markers in both sites. Exploring selective reproductive processes across human infants and research piglets can help us uncover aspects of the cultural production of viability that we would not otherwise see or acknowledge....

  11. Management of Brain Metastases.

    Science.gov (United States)

    Jeyapalan, Suriya A.; Batchelor, Tracy

    2004-07-01

    Advances in neurosurgery and the development of stereotactic radiosurgery have expanded treatment options available for patients with brain metastases. However, despite several randomized clinical trials and multiple uncontrolled studies, there is not a uniform consensus on the best treatment strategy for all patients with brain metastases. The heterogeneity of this patient population in terms of functional status, types of underlying cancers, status of systemic disease control, and number and location of brain metastases make such consensus difficult. Nevertheless, in certain situations, there is Class I evidence that supports one approach or another. The primary objectives in the management of this patient population include improved duration and quality of survival. Very few patients achieve long-term survival after the diagnosis of a brain metastasis.

  12. of brain tumours

    African Journals Online (AJOL)

    outline of the important clinical issues related to brain tumours and psychiatry. ... Left-sided, frontal tumours also seem to be associated with higher rates of depression, while those in the frontal lobe of the right .... Oxford: Blackwell Science,.

  13. Brain versus Machine Control.

    Directory of Open Access Journals (Sweden)

    Jose M Carmena

    2004-12-01

    Full Text Available Dr. Octopus, the villain of the movie "Spiderman 2", is a fusion of man and machine. Neuroscientist Jose Carmena examines the facts behind this fictional account of a brain- machine interface

  14. Brain Basics: Preventing Stroke

    Science.gov (United States)

    ... NINDS) are committed to reducing that burden through biomedical research. What is a Stroke? A stroke, or "brain ... Testimony Legislative Updates Impact NINDS Contributions to Approved Therapies ... Director, Division of Intramural Research

  15. Brain and Addiction

    Science.gov (United States)

    ... reward” circuit, which is part of the limbic system. Normally, the reward circuit responds to feelings of pleasure by releasing ... infographic, discover how drug use affects the brain's reward system. This publication is available for your use and ...

  16. Severe Traumatic Brain Injury

    Science.gov (United States)

    ... TBI Online Concussion Training Press Room Guide to Writing about TBI in News and Social Media Living with TBI HEADS UP to Brain Injury Awareness Get Email Updates To receive email updates about this topic, ...

  17. The neonatal brain

    International Nuclear Information System (INIS)

    Flodmark, O.

    1987-01-01

    The clinical examination of the CNS in the neonate is often difficult in cases of complex pathology. Diagnostic imaging of the neonatal brain has become extremely useful and in the last decade has developed in two main directions: CT and US. MR imaging has been used recently with varying success in the diagnosis of pathology in the neonatal brain. Despite technical difficulties, this imaging method is likely to become increasingly important in the neonate. The paper examines the normal neonatal brain anatomy as seen with the different modalities, followed by pathologic conditions. Attention is directed to the common pathology, in asphyxiated newborns, the patholphysiology of intraventicular hemorrhage and periventricular leukomalacia in the preterm neonate, and hypoxic-ischemic brain injury in the term neonate. Pitfalls, artifacts, and problems in image interpretation are illustrated. Finally, the subsequent appearance of neonatal pathology later in infancy and childhood is discussed

  18. Postnatal brain development

    DEFF Research Database (Denmark)

    Jernigan, Terry L; Baaré, William F C; Stiles, Joan

    2011-01-01

    After birth, there is striking biological and functional development of the brain's fiber tracts as well as remodeling of cortical and subcortical structures. Behavioral development in children involves a complex and dynamic set of genetically guided processes by which neural structures interact...... in children and adolescents, as well as studies that link these changes to behavioral differences. Finally, we discuss evidence for effects on the brain of several factors that may play a role in mediating these brain-behavior associations in children, including genetic variation, behavioral interventions...... constantly with the environment. This is a protracted process, beginning in the third week of gestation and continuing into early adulthood. Reviewed here are studies using structural imaging techniques, with a special focus on diffusion weighted imaging, describing age-related brain maturational changes...

  19. Postnatal brain development

    DEFF Research Database (Denmark)

    Jernigan, Terry L; Baaré, William F C; Stiles, Joan

    2011-01-01

    After birth, there is striking biological and functional development of the brain's fiber tracts as well as remodeling of cortical and subcortical structures. Behavioral development in children involves a complex and dynamic set of genetically guided processes by which neural structures interact...... constantly with the environment. This is a protracted process, beginning in the third week of gestation and continuing into early adulthood. Reviewed here are studies using structural imaging techniques, with a special focus on diffusion weighted imaging, describing age-related brain maturational changes...... in children and adolescents, as well as studies that link these changes to behavioral differences. Finally, we discuss evidence for effects on the brain of several factors that may play a role in mediating these brain-behavior associations in children, including genetic variation, behavioral interventions...

  20. Osmotherapy in brain edema

    DEFF Research Database (Denmark)

    Grände, Per-Olof; Romner, Bertil

    2012-01-01

    Despite the fact that it has been used since the 1960s in diseases associated with brain edema and has been investigated in >150 publications on head injury, very little has been published on the outcome of osmotherapy. We can only speculate whether osmotherapy improves outcome, has no effect......, osmotherapy can be negative for outcome, which may explain why we lack scientific support for its use. These drawbacks, and the fact that the most recent Cochrane meta-analyses of osmotherapy in brain edema and stroke could not find any beneficial effects on outcome, make routine use of osmotherapy in brain...... edema doubtful. Nevertheless, the use of osmotherapy as a temporary measure may be justified to acutely prevent brain stem compression until other measures, such as evacuation of space-occupying lesions or decompressive craniotomy, can be performed. This article is the Con part in a Pro-Con debate...

  1. Brains on video games.

    Science.gov (United States)

    Bavelier, Daphne; Green, C Shawn; Han, Doug Hyun; Renshaw, Perry F; Merzenich, Michael M; Gentile, Douglas A

    2011-11-18

    The popular press is replete with stories about the effects of video and computer games on the brain. Sensationalist headlines claiming that video games 'damage the brain' or 'boost brain power' do not do justice to the complexities and limitations of the studies involved, and create a confusing overall picture about the effects of gaming on the brain. Here, six experts in the field shed light on our current understanding of the positive and negative ways in which playing video games can affect cognition and behaviour, and explain how this knowledge can be harnessed for educational and rehabilitation purposes. As research in this area is still in its early days, the contributors of this Viewpoint also discuss several issues and challenges that should be addressed to move the field forward.

  2. Epigenetics and brain evolution.

    Science.gov (United States)

    Keverne, Eric B

    2011-04-01

    Fundamental aspects of mammalian brain evolution occurred in the context of viviparity and placentation brought about by the epigenetic regulation of imprinted genes. Since the fetal placenta hormonally primes the maternal brain, two genomes in one individual are transgenerationally co-adapted to ensure maternal care and nurturing. Advanced aspects of neocortical brain evolution has shown very few genetic changes between monkeys and humans. Although these lineages diverged at approximately the same time as the rat and mouse (20 million years ago), synonymous sequence divergence between the rat and mouse is double that when comparing monkey with human sequences. Paradoxically, encephalization of rat and mouse are remarkably similar, while comparison of the human and monkey shows the human cortex to be three times the size of the monkey. This suggests an element of genetic stability between the brains of monkey and man with a greater emphasis on epigenetics providing adaptable variability.

  3. Genetics and the Brain

    Science.gov (United States)

    ... Epigenetic regulation of gene expression in physiological and pathological brain processes. Physiol Rev , 2011 Apr; 91(2): ... term potentiation and spine size enlargement. J. Neuroscience , March 18, 2009. 29(11):3395–3403 [xviii] Tapper, ...

  4. Brain Training for Seniors

    Science.gov (United States)

    ... it or lose it” commonly refers to the importance of exercising your body and staying fit. Exercising ... physical exercise can make a difference. Just like physical activity, the earlier you start brain-training activity, the ...

  5. Analysis of Brain Recurrence

    Science.gov (United States)

    Frilot, Clifton; Kim, Paul Y.; Carrubba, Simona; McCarty, David E.; Chesson, Andrew L.; Marino, Andrew A.

    Analysis of Brain Recurrence (ABR) is a method for extracting physiologically significant information from the electroencephalogram (EEG), a non-stationary electrical output of the brain, the ultimate complex dynamical system. ABR permits quantification of temporal patterns in the EEG produced by the non-autonomous differential laws that govern brain metabolism. In the context of appropriate experimental and statistical designs, ABR is ideally suited to the task of interpreting the EEG. Present applications of ABR include discovery of a human magnetic sense, increased mechanistic understanding of neuronal membrane processes, diagnosis of degenerative neurological disease, detection of changes in brain metabolism caused by weak environmental electromagnetic fields, objective characterization of the quality of human sleep, and evaluation of sleep disorders. ABR has important beneficial implications for the development of clinical and experimental neuroscience.

  6. Functional brain imaging; Funktionelle Hirnbildgebung

    Energy Technology Data Exchange (ETDEWEB)

    Gizewski, E.R. [Medizinische Universitaet Innsbruck, Universitaetsklinik fuer Neuroradiologie, Innsbruck (Austria)

    2016-02-15

    Functional magnetic resonance imaging (fMRI) is a non-invasive method that has become one of the major tools for understanding human brain function and in recent years has also been developed for clinical applications. Changes in hemodynamic signals correspond to changes in neuronal activity with good spatial and temporal resolution in fMRI. Using high-field MR systems and increasingly dedicated statistics and postprocessing, activated brain areas can be detected and superimposed on anatomical images. Currently, fMRI data are often combined in multimodal imaging, e. g. with diffusion tensor imaging (DTI) sequences. This method is helping to further understand the physiology of cognitive brain processes and is also being used in a number of clinical applications. In addition to the blood oxygenation level-dependent (BOLD) signals, this article deals with the construction of fMRI investigations, selection of paradigms and evaluation in the clinical routine. Clinically, this method is mainly used in the planning of brain surgery, analyzing the location of brain tumors in relation to eloquent brain areas and the lateralization of language processing. As the BOLD signal is dependent on the strength of the magnetic field as well as other limitations, an overview of recent developments is given. Increases of magnetic field strength (7 T), available head coils and advances in MRI analytical methods have led to constant improvement in fMRI signals and experimental design. Especially the depiction of eloquent brain regions can be done easily and quickly and has become an essential part of presurgical planning. (orig.) [German] Mittlerweile ist die funktionelle MRT (fMRT) eine Methode, die nicht mehr nur in der neurowissenschaftlichen Routine verwendet wird. Die fMRT ermoeglicht die nichtinvasive Darstellung der Hirnaktivitaet in guter raeumlicher und zeitlicher Aufloesung unter Ausnutzung der Durchblutungsaenderung aufgrund der erhoehten Nervenzellaktivitaet. Unter

  7. Negative brain scintigrams in brain tumors

    International Nuclear Information System (INIS)

    Dalke, K.G.

    1978-01-01

    With 53 histologically verified and 2 histologically not identified brain tumors, that showed a negative scintigram, it was tried to find reasons for the wrong and negative dropout of these scintigrams. The electroencephalograms and angiograms, that were made simultaneously were taken into consideration with respect to their propositional capability and were compared with the scintigram findings. For the formation of the negative brain scintigrams there could be found no unique cause or causal constellation. The scintigraphic tumor representation is likely based on a complex process. Therefore the reasons for the negativity of the brain scintigrams can be a manifold of causes. An important role plays the vascularisation of the tumor, but not in a sole way. As well the tumor localisation gains some importance; especially in the temporal lobe or in the deeper structures situated tumors can be negative in the scintigram. To hold down the rate of wrong-negative quote in the case of intracranial tumor search, one is advised to continue with an further exposure after 2 to 4 hours besides the usual exposures, unless a sequential scintigraphy was made from the beginning. (orig./MG) [de

  8. The multilingual brain

    OpenAIRE

    Engel de Abreu, Pascale

    2014-01-01

    The multilingual brain. Is a multilingual education beneficial for children? What are the optimal conditions under which a child can become perfectly multilingual? The given lecture will focus on the "cognitive advantages" of multilingualism and illustrate the impact that being multilingual has on the cognitive organisation of the brain. Practical questions regarding multilingual education will also be discussed. Ass et gutt e Kand méisproocheg ze erzéien? Wat sinn déi optimal Konditio...

  9. Insulin and brain aging

    OpenAIRE

    Baranowska-Bik, Agnieszka; Bik, Wojciech

    2017-01-01

    The world’s population is living much longer than in the past. It is crucial to find as many pathological factors that deteriorate the health condition and well-being of elderly people as possible. Loss of activity and functions over time is typical for elderly people. Aging affects brain function, metabolism and structure in different ways, and these effects have multiple etiologies. Cognitive impairment, impaired neurotransmitter activity and reduction of brain volume are observed in th...

  10. Pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Poussaint, Tina Y. [Department of Radiology, Boston, MA (United States); Panigrahy, Ashok [Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Department of Radiology, Pittsburgh, PA (United States); Huisman, Thierry A.G.M. [Charlotte R. Bloomberg Children' s Center, Johns Hopkins Hospital, Division of Pediatric Radiology and Pediatric Neuroradiology, Baltimore, MD (United States)

    2015-09-15

    Among all causes of death in children from solid tumors, pediatric brain tumors are the most common. This article includes an overview of a subset of infratentorial and supratentorial tumors with a focus on tumor imaging features and molecular advances and treatments of these tumors. Key to understanding the imaging features of brain tumors is a firm grasp of other disease processes that can mimic tumor on imaging. We also review imaging features of a common subset of tumor mimics. (orig.)

  11. Brain derived neurotrophic factor

    DEFF Research Database (Denmark)

    Mitchelmore, Cathy; Gede, Lene

    2014-01-01

    Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies are curre......Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies...

  12. Neuroethics and Brain Privacy

    DEFF Research Database (Denmark)

    Ryberg, Jesper

    2017-01-01

    An introduction is presented in which editor discusses various articles within the issue on topics including ethical challenges with importance of privacy for well-being, impact of brain-reading on mind privacy and neurotechnology.......An introduction is presented in which editor discusses various articles within the issue on topics including ethical challenges with importance of privacy for well-being, impact of brain-reading on mind privacy and neurotechnology....

  13. Protect Your Brain

    Centers for Disease Control (CDC) Podcasts

    Recent high-profile cases among professional athletes have called attention to the serious problem of traumatic brain injuries, or TBI, but the problem isn’t limited to playing fields. In 2009, at least three and a half million people in the U.S. sustained a TBI, either with or without other injuries. In this podcast, Dr. Lisa McGuire discusses the importance of early diagnosis and treatment of brain injuries.

  14. Dyslexia singular brain

    International Nuclear Information System (INIS)

    Habis, M.; Robichon, F.; Demonet, J.F.

    1996-01-01

    Of late ten years, neurologists are studying the brain of the dyslectics. The cerebral imagery (NMR imaging, positron computed tomography) has allowed to confirm the anatomical particularities discovered by some of them: asymmetry default of cerebral hemispheres, size abnormally large of the white substance mass which connect the two hemispheres. The functional imagery, when visualizing this singular brain at work, allows to understand why it labors to reading. (O.M.)

  15. Your Brain and Nervous System

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Your Brain & Nervous System KidsHealth / For Kids / Your Brain & Nervous ... The coolest wetsuit? Nope — he needs his cerebellum! Brain Stem Keeps You Breathing — and More Another brain ...

  16. EDITORIAL: Nanotechnological selection Nanotechnological selection

    Science.gov (United States)

    Demming, Anna

    2013-01-01

    At the nanoscale measures can move from a mass-scale analogue calibration to counters of discrete units. The shift redefines the possible levels of control that can be achieved in a system if adequate selectivity can be imposed. As an example as ionic substances pass through nanoscale pores, the quantity of ions is low enough that the pore can contain either negative or positive ions. Yet precise control over this selectivity still raises difficulties. In this issue researchers address the challenge of how to regulate the ionic selectivity of negative and positive charges with the use of an external charge. The approach may be useful for controlling the behaviour, properties and chemical composition of liquids and has possible technical applications for nanofluidic field effect transistors [1]. Selectivity is a critical advantage in the administration of drugs. Nanoparticles functionalized with targeting moieties can allow delivery of anti-cancer drugs to tumour cells, whilst avoiding healthy cells and hence reducing some of the debilitating side effects of cancer treatments [2]. Researchers in Belarus and the US developed a new theranostic approach—combining therapy and diagnosis—to support the evident benefits of cellular selectivity that can be achieved when nanoparticles are applied in medicine [3]. Their process uses nanobubbles of photothermal vapour, referred to as plasmonic nanobubbles, generated by plasmonic excitations in gold nanoparticles conjugated to diagnosis-specific antibodies. The intracellular plasmonic nanobubbles are controlled by laser fluence so that the response can be tuned in individual living cells. Lower fluence allows non-invasive high-sensitive imaging for diagnosis and higher fluence can disrupt the cellular membrane for treatments. The selective response of carbon nanotubes to different gases has leant them to be used within various different types of sensors, as summarized in a review by researchers at the University of

  17. Regional brain morphometry predicts memory rehabilitation outcome after traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Gary E Strangman

    2010-10-01

    Full Text Available Cognitive deficits following traumatic brain injury (TBI commonly include difficulties with memory, attention, and executive dysfunction. These deficits are amenable to cognitive rehabilitation, but optimally selecting rehabilitation programs for individual patients remains a challenge. Recent methods for quantifying regional brain morphometry allow for automated quantification of tissue volumes in numerous distinct brain structures. We hypothesized that such quantitative structural information could help identify individuals more or less likely to benefit from memory rehabilitation. Fifty individuals with TBI of all severities who reported having memory difficulties first underwent structural MRI scanning. They then participated in a 12 session memory rehabilitation program emphasizing internal memory strategies (I-MEMS. Primary outcome measures (HVLT, RBMT were collected at the time of the MRI scan, immediately following therapy, and again at one month post-therapy. Regional brain volumes were used to predict outcome, adjusting for standard predictors (e.g., injury severity, age, education, pretest scores. We identified several brain regions that provided significant predictions of rehabilitation outcome, including the volume of the hippocampus, the lateral prefrontal cortex, the thalamus, and several subregions of the cingulate cortex. The prediction range of regional brain volumes were in some cases nearly equal in magnitude to prediction ranges provided by pretest scores on the outcome variable. We conclude that specific cerebral networks including these regions may contribute to learning during I-MEMS rehabilitation, and suggest that morphometric measures may provide substantial predictive value for rehabilitation outcome in other cognitive interventions as well.

  18. 99Tcm-Neurolite brain SPECT imaging as an outcome predictor after brain trauma: initial experience

    International Nuclear Information System (INIS)

    Howarth, D.M.; Lan, L.; Booth, G.; Christie, J.; Bookalil, A.; Pollack, M.; Pacey, D.

    1999-01-01

    Full text: The aim of this study was to use semi-quantitative 99 Tc m -ethylene cysteine dimer (Neurolite) cerebral blood flow (CBF) SPET brain imaging to assess its role in predicting outcome after brain trauma. Twelve adult patients (9 males, 3 females) who sustained moderate to severe brain trauma were studied by CBF/SPET within 4 weeks of the injury (scan A) and again after 1 year (scan B). Clinical assessment was also performed at these times and included extensive neuropsychometric testing. Patients received 800-850 MBq 99 Tc m -Neurolite intravenously, and were imaged using a triple-headed gamma camera with LEUHR fan beam collimators. Processing, filtering, reconstruction and data set selection were identical for scans A and B. Semi-quantitative analysis was performed using 25 regions of interest in the cerebral cortex and deep structures in 2 coronal, 2 sagittal and 3 oblique planes. Normalized mean counts per pixel for the whole brain, and regional brain ratios were calculated. Scans A and B were compared and correlated to the clinical outcome data. Two patients with minimal CBF abnormalities made full recoveries. The remaining 10 had moderate to severe focal CBF defects, which showed no significant improvement at 12 months. Of these patients, 2 had moderate disability, 3 had severe to moderate disability and 2 had severe disability at 12 months. Patients with persisting focal abnormal CBF showed persisting neurological deficits. Neurolite brain CBF imaging is a useful method of predicting outcome after moderate to severe head injury

  19. Brain fat embolism

    International Nuclear Information System (INIS)

    Sugiura, Yoshihiro; Kawamura, Yasutaka; Suzuki, Hisato; Yanagimoto, Masahiro; Goto, Yukio

    1994-01-01

    Recently CT and MR imaging have demonstrated that cerebral edema is present in cases of fat embolism syndrome. To simulate this we have made a model of brain-fat embolism in rats under MR imaging. In 20 rats, we did intravenous injection of heparinized blood, 1.5 ml·kg -1 taken from femoral bone marrow cavity. Twenty four hours after the injection, we examined the MR images (1.5 tesla, spin-echo method) of brains and histologic findings of brains and lungs were obtained. In 5 of 20 rats, high signal intensity on T2-weighted images and low signal intensity on T1-weighted images were observed in the area of the unilateral cerebral cortex or hippocampus. These findings showed edema of the brains. They disappeared, however, one week later. Histologic examinations showed massive micro-fat emboli in capillaries of the deep cerebral cortex and substantia nigra, but no edematous findings of the brain were revealed in HE staining. In pulmonary arteries, we also found large fat emboli. We conclude that our model is a useful one for the study of brain fat embolism. (author)