WorldWideScience

Sample records for brain signal representing

  1. Music Composition from the Brain Signal: Representing the Mental State by Music

    Directory of Open Access Journals (Sweden)

    Dan Wu

    2010-01-01

    Full Text Available This paper proposes a method to translate human EEG into music, so as to represent mental state by music. The arousal levels of the brain mental state and music emotion are implicitly used as the bridge between the mind world and the music. The arousal level of the brain is based on the EEG features extracted mainly by wavelet analysis, and the music arousal level is related to the musical parameters such as pitch, tempo, rhythm, and tonality. While composing, some music principles (harmonics and structure were taken into consideration. With EEGs during various sleep stages as an example, the music generated from them had different patterns of pitch, rhythm, and tonality. 35 volunteers listened to the music pieces, and significant difference in music arousal levels was found. It implied that different mental states may be identified by the corresponding music, and so the music from EEG may be a potential tool for EEG monitoring, biofeedback therapy, and so forth.

  2. Music composition from the brain signal: representing the mental state by music.

    Science.gov (United States)

    Wu, Dan; Li, Chaoyi; Yin, Yu; Zhou, Changzheng; Yao, Dezhong

    2010-01-01

    This paper proposes a method to translate human EEG into music, so as to represent mental state by music. The arousal levels of the brain mental state and music emotion are implicitly used as the bridge between the mind world and the music. The arousal level of the brain is based on the EEG features extracted mainly by wavelet analysis, and the music arousal level is related to the musical parameters such as pitch, tempo, rhythm, and tonality. While composing, some music principles (harmonics and structure) were taken into consideration. With EEGs during various sleep stages as an example, the music generated from them had different patterns of pitch, rhythm, and tonality. 35 volunteers listened to the music pieces, and significant difference in music arousal levels was found. It implied that different mental states may be identified by the corresponding music, and so the music from EEG may be a potential tool for EEG monitoring, biofeedback therapy, and so forth.

  3. Notch Signaling and Brain Tumors

    DEFF Research Database (Denmark)

    Stockhausen, Marie; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2011-01-01

    Human brain tumors are a heterogenous group of neoplasms occurring inside the cranium and the central spinal cord. In adults and children, astrocytic glioma and medulloblastoma are the most common subtypes of primary brain tumors. These tumor types are thought to arise from cells in which Notch...... and medulloblastoma. In this chapter we will cover the present findings of Notch signaling in human glioma and medulloblastoma and try to create an overall picture of its relevance in the pathogenesis of these tumors....

  4. Notch Signaling and Brain Tumors

    DEFF Research Database (Denmark)

    Stockhausen, Marie; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2011-01-01

    Human brain tumors are a heterogenous group of neoplasms occurring inside the cranium and the central spinal cord. In adults and children, astrocytic glioma and medulloblastoma are the most common subtypes of primary brain tumors. These tumor types are thought to arise from cells in which Notch...... signaling plays a fundamental role during development. Recent findings have shown that Notch signaling is dysregulated, and contributes to the malignant potential of these tumors. Growing evidence point towards an important role for cancer stem cells in the initiation and maintenance of glioma...... and medulloblastoma. In this chapter we will cover the present findings of Notch signaling in human glioma and medulloblastoma and try to create an overall picture of its relevance in the pathogenesis of these tumors....

  5. Zinc Signal in Brain Diseases

    Directory of Open Access Journals (Sweden)

    Stuart D. Portbury

    2017-11-01

    Full Text Available The divalent cation zinc is an integral requirement for optimal cellular processes, whereby it contributes to the function of over 300 enzymes, regulates intracellular signal transduction, and contributes to efficient synaptic transmission in the central nervous system. Given the critical role of zinc in a breadth of cellular processes, its cellular distribution and local tissue level concentrations remain tightly regulated via a series of proteins, primarily including zinc transporter and zinc import proteins. A loss of function of these regulatory pathways, or dietary alterations that result in a change in zinc homeostasis in the brain, can all lead to a myriad of pathological conditions with both acute and chronic effects on function. This review aims to highlight the role of zinc signaling in the central nervous system, where it may precipitate or potentiate diverse issues such as age-related cognitive decline, depression, Alzheimer’s disease or negative outcomes following brain injury.

  6. Sonic Hedgehog signaling in the mammalian brain.

    Science.gov (United States)

    Traiffort, Elisabeth; Angot, Elodie; Ruat, Martial

    2010-05-01

    The discovery of a Sonic Hedgehog (Shh) signaling pathway in the mature vertebrate CNS has paved the way to the characterization of the functional roles of Shh signals in normal and diseased brain. Shh is proposed to participate in the establishment and maintenance of adult neurogenic niches and to regulate the proliferation of neuronal or glial precursors in several brain areas. Consistent with its role during brain development, misregulation of Shh signaling is associated with tumorigenesis while its recruitement in damaged neural tissue might be part of the regenerating process. This review focuses on the most recent data of the Hedgehog pathway in the adult brain and its relevance as a novel therapeutic approach for brain diseases including brain tumors.

  7. Notch Signaling and Brain Tumors

    DEFF Research Database (Denmark)

    Stockhausen, Marie; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2011-01-01

    Human brain tumors are a heterogenous group of neoplasms occurring inside the cranium and the central spinal cord. In adults and children, astrocytic glioma and medulloblastoma are the most common subtypes of primary brain tumors. These tumor types are thought to arise from cells in which Notch s...

  8. Statistical Challenges in Modeling Big Brain Signals

    KAUST Repository

    Yu, Zhaoxia

    2017-11-01

    Brain signal data are inherently big: massive in amount, complex in structure, and high in dimensions. These characteristics impose great challenges for statistical inference and learning. Here we review several key challenges, discuss possible solutions, and highlight future research directions.

  9. Statistical Challenges in Modeling Big Brain Signals

    OpenAIRE

    Yu, Zhaoxia; Pluta, Dustin; Shen, Tong; Chen, Chuansheng; Xue, Gui; Ombao, Hernando

    2017-01-01

    Brain signal data are inherently big: massive in amount, complex in structure, and high in dimensions. These characteristics impose great challenges for statistical inference and learning. Here we review several key challenges, discuss possible solutions, and highlight future research directions.

  10. Artifact suppression and analysis of brain activities with electroencephalography signals

    Science.gov (United States)

    Rashed-Al-Mahfuz, Md.; Islam, Md. Rabiul; Hirose, Keikichi; Molla, Md. Khademul Islam

    2013-01-01

    Brain-computer interface is a communication system that connects the brain with computer (or other devices) but is not dependent on the normal output of the brain (i.e., peripheral nerve and muscle). Electro-oculogram is a dominant artifact which has a significant negative influence on further analysis of real electroencephalography data. This paper presented a data adaptive technique for artifact suppression and brain wave extraction from electroencephalography signals to detect regional brain activities. Empirical mode decomposition based adaptive thresholding approach was employed here to suppress the electro-oculogram artifact. Fractional Gaussian noise was used to determine the threshold level derived from the analysis data without any training. The purified electroencephalography signal was composed of the brain waves also called rhythmic components which represent the brain activities. The rhythmic components were extracted from each electroencephalography channel using adaptive wiener filter with the original scale. The regional brain activities were mapped on the basis of the spatial distribution of rhythmic components, and the results showed that different regions of the brain are activated in response to different stimuli. This research analyzed the activities of a single rhythmic component, alpha with respect to different motor imaginations. The experimental results showed that the proposed method is very efficient in artifact suppression and identifying individual motor imagery based on the activities of alpha component. PMID:25206446

  11. Estimating Neural Signal Dynamics in the Human Brain

    Directory of Open Access Journals (Sweden)

    Christopher W Tyler

    2011-06-01

    Full Text Available Although brain imaging methods are highly effective for localizing the effects of neural activation throughout the human brain in terms of the blood oxygenation level dependent (BOLD response, there is currently no way to estimate the underlying neural signal dynamics in generating the BOLD response in each local activation region (except for processes slower than the BOLD time course. Knowledge of the neural signal is critical information if spatial mapping is to progress to the analysis of dynamic information flow through the cortical networks as the brain performs its tasks. We introduce an analytic approach that provides a new level of conceptualization and specificity in the study of brain processing by noninvasive methods. This technique allows us to use brain imaging methods to determine the dynamics of local neural population responses to their native temporal resolution throughout the human brain, with relatively narrow confidence intervals on many response properties. The ability to characterize local neural dynamics in the human brain represents a significant enhancement of brain imaging capabilities, with potential application from general cognitive studies to assessment of neuropathologies.

  12. Integrating Retinoic Acid Signaling with Brain Function

    Science.gov (United States)

    Luo, Tuanlian; Wagner, Elisabeth; Drager, Ursula C.

    2009-01-01

    The vitamin A derivative retinoic acid (RA) regulates the transcription of about a 6th of the human genome. Compelling evidence indicates a role of RA in cognitive activities, but its integration with the molecular mechanisms of higher brain functions is not known. Here we describe the properties of RA signaling in the mouse, which point to…

  13. Obesity-Induced Hypertension: Brain Signaling Pathways

    Science.gov (United States)

    da Silva, Alexandre A.; Wang, Zhen; Fang, Taolin; Aberdein, Nicola; de Lara Rodriguez, Cecilia E. P.; Hall, John E.

    2017-01-01

    Obesity greatly increases the risk for cardiovascular, metabolic, and renal diseases and is one of the most significant and preventable causes of increased blood pressure (BP) in patients with essential hypertension. This review high-lights recent advances in our understanding of central nervous system (CNS) signaling pathways that contribute to the etiology and pathogenesis of obesity-induced hypertension. We discuss the role of excess adiposity and activation of the brain leptin-melanocortin system in causing increased sympathetic activity in obesity. In addition, we highlight other potential brain mechanisms by which increased weight gain modulates metabolic and cardiovascular functions. Unraveling the CNS mechanisms responsible for increased sympathetic activation and hypertension and how circulating hormones activate brain signaling pathways to control BP offer potentially important therapeutic targets for obesity and hypertension. PMID:27262997

  14. Obesity-Induced Hypertension: Brain Signaling Pathways.

    Science.gov (United States)

    do Carmo, Jussara M; da Silva, Alexandre A; Wang, Zhen; Fang, Taolin; Aberdein, Nicola; de Lara Rodriguez, Cecilia E P; Hall, John E

    2016-07-01

    Obesity greatly increases the risk for cardiovascular, metabolic, and renal diseases and is one of the most significant and preventable causes of increased blood pressure (BP) in patients with essential hypertension. This review highlights recent advances in our understanding of central nervous system (CNS) signaling pathways that contribute to the etiology and pathogenesis of obesity-induced hypertension. We discuss the role of excess adiposity and activation of the brain leptin-melanocortin system in causing increased sympathetic activity in obesity. In addition, we highlight other potential brain mechanisms by which increased weight gain modulates metabolic and cardiovascular functions. Unraveling the CNS mechanisms responsible for increased sympathetic activation and hypertension and how circulating hormones activate brain signaling pathways to control BP offer potentially important therapeutic targets for obesity and hypertension.

  15. Modeling high dimensional multichannel brain signals

    KAUST Repository

    Hu, Lechuan

    2017-03-27

    In this paper, our goal is to model functional and effective (directional) connectivity in network of multichannel brain physiological signals (e.g., electroencephalograms, local field potentials). The primary challenges here are twofold: first, there are major statistical and computational difficulties for modeling and analyzing high dimensional multichannel brain signals; second, there is no set of universally-agreed measures for characterizing connectivity. To model multichannel brain signals, our approach is to fit a vector autoregressive (VAR) model with sufficiently high order so that complex lead-lag temporal dynamics between the channels can be accurately characterized. However, such a model contains a large number of parameters. Thus, we will estimate the high dimensional VAR parameter space by our proposed hybrid LASSLE method (LASSO+LSE) which is imposes regularization on the first step (to control for sparsity) and constrained least squares estimation on the second step (to improve bias and mean-squared error of the estimator). Then to characterize connectivity between channels in a brain network, we will use various measures but put an emphasis on partial directed coherence (PDC) in order to capture directional connectivity between channels. PDC is a directed frequency-specific measure that explains the extent to which the present oscillatory activity in a sender channel influences the future oscillatory activity in a specific receiver channel relative all possible receivers in the network. Using the proposed modeling approach, we have achieved some insights on learning in a rat engaged in a non-spatial memory task.

  16. Generate the scale-free brain music from BOLD signals.

    Science.gov (United States)

    Lu, Jing; Guo, Sijia; Chen, Mingming; Wang, Weixia; Yang, Hua; Guo, Daqing; Yao, Dezhong

    2018-01-01

    Many methods have been developed to translate a human electroencephalogram (EEG) into music. In addition to EEG, functional magnetic resonance imaging (fMRI) is another method used to study the brain and can reflect physiological processes. In 2012, we established a method to use simultaneously recorded fMRI and EEG signals to produce EEG-fMRI music, which represents a step toward scale-free brain music. In this study, we used a neural mass model, the Jansen-Rit model, to simulate activity in several cortical brain regions. The interactions between different brain regions were represented by the average normalized diffusion tensor imaging (DTI) structural connectivity with a coupling coefficient that modulated the coupling strength. Seventy-eight brain regions were adopted from the Automated Anatomical Labeling (AAL) template. Furthermore, we used the Balloon-Windkessel hemodynamic model to transform neural activity into a blood-oxygen-level dependent (BOLD) signal. Because the fMRI BOLD signal changes slowly, we used a sampling rate of 250 Hz to produce the temporal series for music generation. Then, the BOLD music was generated for each region using these simulated BOLD signals. Because the BOLD signal is scale free, these music pieces were also scale free, which is similar to classic music. Here, to simulate the case of an epileptic patient, we changed the parameter that determined the amplitude of the excitatory postsynaptic potential (EPSP) in the neural mass model. Finally, we obtained BOLD music for healthy and epileptic patients. The differences in levels of arousal between the 2 pieces of music may provide a potential tool for discriminating the different populations if the differences can be confirmed by more real data. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  17. Obesity-Induced Hypertension: Brain Signaling Pathways

    OpenAIRE

    do Carmo, Jussara M.; da Silva, Alexandre A.; Wang, Zhen; Fang, Taolin; Aberdein, Nicola; de Lara Rodriguez, Cecilia E. P.; Hall, John E.

    2016-01-01

    Obesity greatly increases the risk for cardiovascular, metabolic, and renal diseases and is one of the most significant and preventable causes of increased blood pressure (BP) in patients with essential hypertension. This review high-lights recent advances in our understanding of central nervous system (CNS) signaling pathways that contribute to the etiology and pathogenesis of obesity-induced hypertension. We discuss the role of excess adiposity and activation of the brain leptin-melanocorti...

  18. Modeling High-Dimensional Multichannel Brain Signals

    KAUST Repository

    Hu, Lechuan

    2017-12-12

    Our goal is to model and measure functional and effective (directional) connectivity in multichannel brain physiological signals (e.g., electroencephalograms, local field potentials). The difficulties from analyzing these data mainly come from two aspects: first, there are major statistical and computational challenges for modeling and analyzing high-dimensional multichannel brain signals; second, there is no set of universally agreed measures for characterizing connectivity. To model multichannel brain signals, our approach is to fit a vector autoregressive (VAR) model with potentially high lag order so that complex lead-lag temporal dynamics between the channels can be captured. Estimates of the VAR model will be obtained by our proposed hybrid LASSLE (LASSO + LSE) method which combines regularization (to control for sparsity) and least squares estimation (to improve bias and mean-squared error). Then we employ some measures of connectivity but put an emphasis on partial directed coherence (PDC) which can capture the directional connectivity between channels. PDC is a frequency-specific measure that explains the extent to which the present oscillatory activity in a sender channel influences the future oscillatory activity in a specific receiver channel relative to all possible receivers in the network. The proposed modeling approach provided key insights into potential functional relationships among simultaneously recorded sites during performance of a complex memory task. Specifically, this novel method was successful in quantifying patterns of effective connectivity across electrode locations, and in capturing how these patterns varied across trial epochs and trial types.

  19. What is a representative brain? Neuroscience meets population science.

    Science.gov (United States)

    Falk, Emily B; Hyde, Luke W; Mitchell, Colter; Faul, Jessica; Gonzalez, Richard; Heitzeg, Mary M; Keating, Daniel P; Langa, Kenneth M; Martz, Meghan E; Maslowsky, Julie; Morrison, Frederick J; Noll, Douglas C; Patrick, Megan E; Pfeffer, Fabian T; Reuter-Lorenz, Patricia A; Thomason, Moriah E; Davis-Kean, Pamela; Monk, Christopher S; Schulenberg, John

    2013-10-29

    The last decades of neuroscience research have produced immense progress in the methods available to understand brain structure and function. Social, cognitive, clinical, affective, economic, communication, and developmental neurosciences have begun to map the relationships between neuro-psychological processes and behavioral outcomes, yielding a new understanding of human behavior and promising interventions. However, a limitation of this fast moving research is that most findings are based on small samples of convenience. Furthermore, our understanding of individual differences may be distorted by unrepresentative samples, undermining findings regarding brain-behavior mechanisms. These limitations are issues that social demographers, epidemiologists, and other population scientists have tackled, with solutions that can be applied to neuroscience. By contrast, nearly all social science disciplines, including social demography, sociology, political science, economics, communication science, and psychology, make assumptions about processes that involve the brain, but have incorporated neural measures to differing, and often limited, degrees; many still treat the brain as a black box. In this article, we describe and promote a perspective--population neuroscience--that leverages interdisciplinary expertise to (i) emphasize the importance of sampling to more clearly define the relevant populations and sampling strategies needed when using neuroscience methods to address such questions; and (ii) deepen understanding of mechanisms within population science by providing insight regarding underlying neural mechanisms. Doing so will increase our confidence in the generalizability of the findings. We provide examples to illustrate the population neuroscience approach for specific types of research questions and discuss the potential for theoretical and applied advances from this approach across areas.

  20. What is a representative brain? Neuroscience meets population science

    Science.gov (United States)

    Falk, Emily B.; Hyde, Luke W.; Mitchell, Colter; Faul, Jessica; Gonzalez, Richard; Heitzeg, Mary M.; Keating, Daniel P.; Langa, Kenneth M.; Martz, Meghan E.; Maslowsky, Julie; Morrison, Frederick J.; Noll, Douglas C.; Patrick, Megan E.; Pfeffer, Fabian T.; Reuter-Lorenz, Patricia A.; Thomason, Moriah E.; Davis-Kean, Pamela; Monk, Christopher S.; Schulenberg, John

    2013-01-01

    The last decades of neuroscience research have produced immense progress in the methods available to understand brain structure and function. Social, cognitive, clinical, affective, economic, communication, and developmental neurosciences have begun to map the relationships between neuro-psychological processes and behavioral outcomes, yielding a new understanding of human behavior and promising interventions. However, a limitation of this fast moving research is that most findings are based on small samples of convenience. Furthermore, our understanding of individual differences may be distorted by unrepresentative samples, undermining findings regarding brain–behavior mechanisms. These limitations are issues that social demographers, epidemiologists, and other population scientists have tackled, with solutions that can be applied to neuroscience. By contrast, nearly all social science disciplines, including social demography, sociology, political science, economics, communication science, and psychology, make assumptions about processes that involve the brain, but have incorporated neural measures to differing, and often limited, degrees; many still treat the brain as a black box. In this article, we describe and promote a perspective—population neuroscience—that leverages interdisciplinary expertise to (i) emphasize the importance of sampling to more clearly define the relevant populations and sampling strategies needed when using neuroscience methods to address such questions; and (ii) deepen understanding of mechanisms within population science by providing insight regarding underlying neural mechanisms. Doing so will increase our confidence in the generalizability of the findings. We provide examples to illustrate the population neuroscience approach for specific types of research questions and discuss the potential for theoretical and applied advances from this approach across areas. PMID:24151336

  1. Emotion Walking for Humanoid Avatars Using Brain Signals

    Directory of Open Access Journals (Sweden)

    Ahmad Hoirul Basori

    2013-01-01

    Full Text Available Interaction between humans and humanoid avatar representations is very important in virtual reality and robotics, since the humanoid avatar can represent either a human or a robot in a virtual environment. Many researchers have focused on providing natural interactions for humanoid avatars or even for robots with the use of camera tracking, gloves, giving them the ability to speak, brain interfaces and other devices. This paper provides a new multimodal interaction control for avatars by combining brain signals, facial muscle tension recognition and glove tracking to change the facial expression of humanoid avatars according to the user's emotional condition. The signals from brain activity and muscle movements are used as the emotional stimulator, while the glove acts as emotion intensity control for the avatar. This multimodal interface can determine when the humanoid avatar needs to change their facial expression or their walking power. The results show that humanoid avatar have different timelines of walking and facial expressions when the user stimulates them with different emotions. This finding is believed to provide new knowledge on controlling robots' and humanoid avatars' facial expressions and walking.

  2. Harnessing Prefrontal Cognitive Signals for Brain-Machine Interfaces.

    Science.gov (United States)

    Min, Byoung-Kyong; Chavarriaga, Ricardo; Millán, José Del R

    2017-07-01

    Brain-machine interfaces (BMIs) enable humans to interact with devices by modulating their brain signals. Despite impressive technological advancements, several obstacles remain. The most commonly used BMI control signals are derived from the brain areas involved in primary sensory- or motor-related processing. However, these signals only reflect a limited range of human intentions. Therefore, additional sources of brain activity for controlling BMIs need to be explored. In particular, higher-order cognitive brain signals, specifically those encoding goal-directed intentions, are natural candidates for enlarging the repertoire of BMI control signals and making them more efficient and intuitive. Thus, here, we identify the prefrontal brain area as a key target region for future BMIs, given its involvement in higher-order, goal-oriented cognitive processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Lactate transport and signaling in the brain

    DEFF Research Database (Denmark)

    Bergersen, Linda Hildegard

    2015-01-01

    , such as in physical exercise, there is net influx of lactate from blood to brain, where the lactate is used for energy production and myelin formation. Lactate binds to the lactate receptor GPR81 aka hydroxycarboxylic acid receptor (HCAR1) on brain cells and cerebral blood vessels, and regulates the levels of c...... of the favorable effects on the brain resulting from physical exercise....... to some, lactate is a preferred fuel for brain metabolism. Immediately after brain activation, the rate of glycolysis exceeds oxidation, leading to net production of lactate. At physical rest, there is a net efflux of lactate from the brain into the blood stream. But when blood lactate levels rise...

  4. Cerebral insulin, insulin signaling pathway, and brain angiogenesis.

    Science.gov (United States)

    Zeng, Yi; Zhang, Le; Hu, Zhiping

    2016-01-01

    Insulin performs unique non-metabolic functions within the brain. Broadly speaking, two major areas of these functions are those related to brain endothelial cells and the blood-brain barrier (BBB) function, and those related to behavioral effects, like cognition in disease states (Alzheimer's disease, AD) and in health. Recent studies showed that both these functions are associated with brain angiogenesis. These findings raise interesting questions such as how they are linked to each other and whether modifying brain angiogenesis by targeting certain insulin signaling pathways could be an effective strategy to treat dementia as in AD, or even to help secure healthy longevity. The two canonical downstream pathways involved in mediating the insulin signaling pathway, the phosphoinositide-3 kinase (PI3K), and mitogen-activated protein kinase (MAPK) cascades, in the brain are supposed to be similar to those in the periphery. PI3K and MAPK pathways play important roles in angiogenesis. Both are involved in stimulating hypoxia inducible factor (HIF) in angiogenesis and could be activated by the insulin signaling pathway. This suggests that PI3K and MAPK pathways might act as cross-talk between the insulin signaling pathway and the angiogenesis pathway in brain. But the cerebral insulin, insulin signaling pathway, and the detailed mechanism in the connection of insulin signaling pathway, brain angiogenesis pathway, and healthy aging or dementias are still mostly not clear and need further studies.

  5. Brain signal complexity rises with repetition suppression in visual learning.

    Science.gov (United States)

    Lafontaine, Marc Philippe; Lacourse, Karine; Lina, Jean-Marc; McIntosh, Anthony R; Gosselin, Frédéric; Théoret, Hugo; Lippé, Sarah

    2016-06-21

    Neuronal activity associated with visual processing of an unfamiliar face gradually diminishes when it is viewed repeatedly. This process, known as repetition suppression (RS), is involved in the acquisition of familiarity. Current models suggest that RS results from interactions between visual information processing areas located in the occipito-temporal cortex and higher order areas, such as the dorsolateral prefrontal cortex (DLPFC). Brain signal complexity, which reflects information dynamics of cortical networks, has been shown to increase as unfamiliar faces become familiar. However, the complementarity of RS and increases in brain signal complexity have yet to be demonstrated within the same measurements. We hypothesized that RS and brain signal complexity increase occur simultaneously during learning of unfamiliar faces. Further, we expected alteration of DLPFC function by transcranial direct current stimulation (tDCS) to modulate RS and brain signal complexity over the occipito-temporal cortex. Participants underwent three tDCS conditions in random order: right anodal/left cathodal, right cathodal/left anodal and sham. Following tDCS, participants learned unfamiliar faces, while an electroencephalogram (EEG) was recorded. Results revealed RS over occipito-temporal electrode sites during learning, reflected by a decrease in signal energy, a measure of amplitude. Simultaneously, as signal energy decreased, brain signal complexity, as estimated with multiscale entropy (MSE), increased. In addition, prefrontal tDCS modulated brain signal complexity over the right occipito-temporal cortex during the first presentation of faces. These results suggest that although RS may reflect a brain mechanism essential to learning, complementary processes reflected by increases in brain signal complexity, may be instrumental in the acquisition of novel visual information. Such processes likely involve long-range coordinated activity between prefrontal and lower order visual

  6. Long-Distance Retinoid Signaling in the Zebra Finch Brain

    Science.gov (United States)

    Roeske, Tina C.; Scharff, Constance; Olson, Christopher R.; Nshdejan, Arpik; Mello, Claudio V.

    2014-01-01

    All-trans retinoic acid (ATRA), the main active metabolite of vitamin A, is a powerful signaling molecule that regulates large-scale morphogenetic processes during vertebrate embryonic development, but is also involved post-natally in regulating neural plasticity and cognition. In songbirds, it plays an important role in the maturation of learned song. The distribution of the ATRA-synthesizing enzyme, zRalDH, and of ATRA receptors (RARs) have been described, but information on the distribution of other components of the retinoid signaling pathway is still lacking. To address this gap, we have determined the expression patterns of two obligatory RAR co-receptors, the retinoid X receptors (RXR) α and γ, and of the three ATRA-degrading cytochromes CYP26A1, CYP26B1, and CYP26C1. We have also studied the distribution of zRalDH protein using immunohistochemistry, and generated a refined map of ATRA localization, using a modified reporter cell assay to examine entire brain sections. Our results show that (1) ATRA is more broadly distributed in the brain than previously predicted by the spatially restricted distribution of zRalDH transcripts. This could be due to long-range transport of zRalDH enzyme between different nuclei of the song system: Experimental lesions of putative zRalDH peptide source regions diminish ATRA-induced transcription in target regions. (2) Four telencephalic song nuclei express different and specific subsets of retinoid-related receptors and could be targets of retinoid regulation; in the case of the lateral magnocellular nucleus of the anterior nidopallium (lMAN), receptor expression is dynamically regulated in a circadian and age-dependent manner. (3) High-order auditory areas exhibit a complex distribution of transcripts representing ATRA synthesizing and degrading enzymes and could also be a target of retinoid signaling. Together, our survey across multiple connected song nuclei and auditory brain regions underscores the prominent role of

  7. Long-distance retinoid signaling in the zebra finch brain.

    Directory of Open Access Journals (Sweden)

    Tina C Roeske

    Full Text Available All-trans retinoic acid (ATRA, the main active metabolite of vitamin A, is a powerful signaling molecule that regulates large-scale morphogenetic processes during vertebrate embryonic development, but is also involved post-natally in regulating neural plasticity and cognition. In songbirds, it plays an important role in the maturation of learned song. The distribution of the ATRA-synthesizing enzyme, zRalDH, and of ATRA receptors (RARs have been described, but information on the distribution of other components of the retinoid signaling pathway is still lacking. To address this gap, we have determined the expression patterns of two obligatory RAR co-receptors, the retinoid X receptors (RXR α and γ, and of the three ATRA-degrading cytochromes CYP26A1, CYP26B1, and CYP26C1. We have also studied the distribution of zRalDH protein using immunohistochemistry, and generated a refined map of ATRA localization, using a modified reporter cell assay to examine entire brain sections. Our results show that (1 ATRA is more broadly distributed in the brain than previously predicted by the spatially restricted distribution of zRalDH transcripts. This could be due to long-range transport of zRalDH enzyme between different nuclei of the song system: Experimental lesions of putative zRalDH peptide source regions diminish ATRA-induced transcription in target regions. (2 Four telencephalic song nuclei express different and specific subsets of retinoid-related receptors and could be targets of retinoid regulation; in the case of the lateral magnocellular nucleus of the anterior nidopallium (lMAN, receptor expression is dynamically regulated in a circadian and age-dependent manner. (3 High-order auditory areas exhibit a complex distribution of transcripts representing ATRA synthesizing and degrading enzymes and could also be a target of retinoid signaling. Together, our survey across multiple connected song nuclei and auditory brain regions underscores the

  8. Role of retinoid signalling in the adult brain.

    Science.gov (United States)

    Lane, Michelle A; Bailey, Sarah J

    2005-03-01

    Vitamin A (all-trans-retinol) is the parent compound of a family of natural and synthetic compounds, the retinoids. Retinoids regulate gene transcription in numerous cells and tissues by binding to nuclear retinoid receptor proteins, which act as transcription factors. Much of the research conducted on retinoid signalling in the nervous system has focussed on developmental effects in the embryonic or early postnatal brain. Here, we review the increasing body of evidence indicating that retinoid signalling plays an important role in the function of the mature brain. Components of the metabolic pathway for retinoids have been identified in adult brain tissues, suggesting that all-trans-retinoic acid (ATRA) can be synthesized in discrete regions of the brain. The distribution of retinoid receptor proteins in the adult nervous system is different from that seen during development; and suggests that retinoid signalling is likely to have a physiological role in adult cortex, amygdala, hypothalamus, hippocampus, striatum and associated brain regions. A number of neuronal specific genes contain recognition sequences for the retinoid receptor proteins and can be directly regulated by retinoids. Disruption of retinoid signalling pathways in rodent models indicates their involvement in regulating synaptic plasticity and associated learning and memory behaviours. Retinoid signalling pathways have also been implicated in the pathophysiology of Alzheimer's disease, schizophrenia and depression. Overall, the data underscore the likely importance of adequate nutritional Vitamin A status for adult brain function and highlight retinoid signalling pathways as potential novel therapeutic targets for neurological diseases.

  9. Beyond distance and direction: the brain represents target locations non-metrically.

    Science.gov (United States)

    Thaler, Lore; Goodale, Melvyn A

    2010-03-23

    In their day-to-day activities human beings are constantly generating behavior, such as pointing, grasping or verbal reports, on the basis of visible target locations. The question arises how the brain represents target locations. One possibility is that the brain represents them metrically, i.e. in terms of distance and direction. Another equally plausible possibility is that the brain represents locations non-metrically, using for example ordered geometry or topology. Here we report two experiments that were designed to test if the brain represents locations metrically or non-metrically. We measured accuracy and variability of visually guided reach-to-point movements (Experiment 1) and probe-stimulus adjustments (Experiment 2). The specific procedure of informing subjects about the relevant response on each trial enabled us to dissociate the use of non-metric target location from the use of metric distance and direction in head/eye-centered, hand-centered and externally defined (allocentric) coordinates. The behavioral data show that subjects' responses are least variable when they can direct their response at a visible target location, the only condition that permitted the use of non-metric information about target location in our experiments. Data from Experiments 1 and 2 correspond well quantitatively. Response variability in non-metric conditions cannot be predicted based on response variability in metric conditions. We conclude that the brain uses non-metric geometrical structure to represent locations.

  10. Abnormalities of Dopamine D Receptor Signaling in the Diseased Brain

    Directory of Open Access Journals (Sweden)

    G Aleph Prieto

    2017-08-01

    Full Text Available Dopamine D 3 receptors (D 3 R modulate neuronal activity in several brain regions including cortex, striatum, cerebellum, and hippocampus. A growing body of evidence suggests that aberrant D 3 R signaling contributes to multiple brain diseases, such as Parkinson’s disease, essential tremor, schizophrenia, and addiction. In line with these findings, D 3 R has emerged as a potential target in the treatment of neurological disorders. However, the mechanisms underlying neuronal D 3 R signaling are poorly understood, either in healthy or diseased brain. Here, I review the molecular mechanisms involved in D 3 R signaling via monomeric D 3 R and heteromeric receptor complexes (e.g., D 3 R-D 1 R, D 3 R-D 2 R, D 3 R-A 2a R, and D 3 R-D 3 nf. I focus on D 3 R signaling pathways that, according to recent reports, contribute to pathological brain states. In particular, I describe evidence on both quantitative (e.g., increased number or affinity and qualitative (e.g., switched signaling changes in D 3 R that has been associated with brain dysfunction. I conclude with a description of basic mechanisms that modulate D 3 R signaling such as desensitization, as disruption of these mechanisms may underlie pathological changes in D 3 R signaling. Because several lines of evidence support the idea that imbalances in D 3 R signaling alter neural function, a better understanding of downstream D 3 R pathways is likely to reveal novel therapeutic strategies toward dopamine-related brain disorders.

  11. FGF signaling is required for brain left-right asymmetry and brain midline formation.

    Science.gov (United States)

    Neugebauer, Judith M; Yost, H Joseph

    2014-02-01

    Early disruption of FGF signaling alters left-right (LR) asymmetry throughout the embryo. Here we uncover a role for FGF signaling that specifically disrupts brain asymmetry, independent of normal lateral plate mesoderm (LPM) asymmetry. When FGF signaling is inhibited during mid-somitogenesis, asymmetrically expressed LPM markers southpaw and lefty2 are not affected. However, asymmetrically expressed brain markers lefty1 and cyclops become bilateral. We show that FGF signaling controls expression of six3b and six7, two transcription factors required for repression of asymmetric lefty1 in the brain. We found that Z0-1, atypical PKC (aPKC) and β-catenin protein distribution revealed a midline structure in the forebrain that is dependent on a balance of FGF signaling. Ectopic activation of FGF signaling leads to overexpression of six3b, loss of organized midline adherins junctions and bilateral loss of lefty1 expression. Reducing FGF signaling leads to a reduction in six3b and six7 expression, an increase in cell boundary formation in the brain midline, and bilateral expression of lefty1. Together, these results suggest a novel role for FGF signaling in the brain to control LR asymmetry, six transcription factor expressions, and a midline barrier structure. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Predictive brain signals of linguistic development

    Directory of Open Access Journals (Sweden)

    Valesca eKooijman

    2013-02-01

    Full Text Available The ability to extract word forms from continuous speech is a prerequisite for constructing a vocabulary and emerges in the first year of life. Electrophysiological (ERP studies of speech segmentation by nine- to 12-month-old listeners in several languages have found a left-localized negativity linked to word onset as a marker of word detection. We report an ERP study showing significant evidence of speech segmentation in Dutch-learning seven-month-olds. In contrast to the left-localized negative effect reported with older infants, the observed overall mean effect had a positive polarity. Inspection of individual results revealed two participant sub-groups: a majority showing a positive-going response, and a minority showing the left negativity observed in older age groups. We retested participants at age three, on vocabulary comprehension and word and sentence production. On every test, children who at seven months had shown the negativity associated with segmentation of words from speech outperformed those who had produced positive-going brain responses to the same input. The earlier that infants show the left-localized brain responses typically indicating detection of words in speech, the better their early childhood language skills.

  13. Exploring EEG signals in a Brain-Computer Interface

    Science.gov (United States)

    Zubrycki, Paweł; Mulawka, Jan

    2014-11-01

    This article shows the basic methods of electroencephalography EEG signal exploration. It contains information about data acquisition and different methods in which brain-computer interfaces can be made. The main focus of the paper is to find a way to determine the best set of parameters to detect movement of a hand in EEG signal. In the introduction there is also short introduction to EEG as well as fundamentals of support vector machine.

  14. Physiological properties of brain-machine interface input signals.

    Science.gov (United States)

    Slutzky, Marc W; Flint, Robert D

    2017-08-01

    Brain-machine interfaces (BMIs), also called brain-computer interfaces (BCIs), decode neural signals and use them to control some type of external device. Despite many experimental successes and terrific demonstrations in animals and humans, a high-performance, clinically viable device has not yet been developed for widespread usage. There are many factors that impact clinical viability and BMI performance. Arguably, the first of these is the selection of brain signals used to control BMIs. In this review, we summarize the physiological characteristics and performance-including movement-related information, longevity, and stability-of multiple types of input signals that have been used in invasive BMIs to date. These include intracortical spikes as well as field potentials obtained inside the cortex, at the surface of the cortex (electrocorticography), and at the surface of the dura mater (epidural signals). We also discuss the potential for future enhancements in input signal performance, both by improving hardware and by leveraging the knowledge of the physiological characteristics of these signals to improve decoding and stability. Copyright © 2017 the American Physiological Society.

  15. GABAergic interneuron to astrocyte signalling: a neglected form of cell communication in the brain

    Science.gov (United States)

    Losi, Gabriele; Mariotti, Letizia; Carmignoto, Giorgio

    2014-01-01

    GABAergic interneurons represent a minority of all cortical neurons and yet they efficiently control neural network activities in all brain areas. In parallel, glial cell astrocytes exert a broad control of brain tissue homeostasis and metabolism, modulate synaptic transmission and contribute to brain information processing in a dynamic interaction with neurons that is finely regulated in time and space. As most studies have focused on glutamatergic neurons and excitatory transmission, our knowledge of functional interactions between GABAergic interneurons and astrocytes is largely defective. Here, we critically discuss the currently available literature that hints at a potential relevance of this specific signalling in brain function. Astrocytes can respond to GABA through different mechanisms that include GABA receptors and transporters. GABA-activated astrocytes can, in turn, modulate local neuronal activity by releasing gliotransmitters including glutamate and ATP. In addition, astrocyte activation by different signals can modulate GABAergic neurotransmission. Full clarification of the reciprocal signalling between different GABAergic interneurons and astrocytes will improve our understanding of brain network complexity and has the potential to unveil novel therapeutic strategies for brain disorders. PMID:25225102

  16. Tutorial: Signal Processing in Brain-Computer Interfaces

    NARCIS (Netherlands)

    Garcia Molina, G.

    2010-01-01

    Research in Electroencephalogram (EEG) based Brain-Computer Interfaces (BCIs) has been considerably expanding during the last few years. Such an expansion owes to a large extent to the multidisciplinary and challenging nature of BCI research. Signal processing undoubtedly constitutes an essential

  17. Molecular Mechanisms of Cannabis Signaling in the Brain.

    Science.gov (United States)

    Ronan, Patrick J; Wongngamnit, Narin; Beresford, Thomas P

    2016-01-01

    Cannabis has been cultivated and used by humans for thousands of years. Research for decades was focused on understanding the mechanisms of an illegal/addictive drug. This led to the discovery of the vast endocannabinoid system. Research has now shifted to understanding fundamental biological questions related to one of the most widespread signaling systems in both the brain and the body. Our understanding of cannabinoid signaling has advanced significantly in the last two decades. In this review, we discuss the state of knowledge on mechanisms of Cannabis signaling in the brain and the modulation of key brain neurotransmitter systems involved in both brain reward/addiction and psychiatric disorders. It is highly probable that various cannabinoids will be found to be efficacious in the treatment of a number of psychiatric disorders. However, while there is clearly much potential, marijuana has not been properly vetted by the medical-scientific evaluation process and there are clearly a range of potentially adverse side-effects-including addiction. We are at crossroads for research on endocannabinoid function and therapeutics (including the use of exogenous treatments such as Cannabis). With over 100 cannabinoid constituents, the majority of which have not been studied, there is much Cannabis research yet to be done. With more states legalizing both the medicinal and recreational use of marijuana the rigorous scientific investigation into cannabinoid signaling is imperative. Copyright © 2016. Published by Elsevier Inc.

  18. Selection of independent components representing event-related brain potentials: a data-driven approach for greater objectivity.

    Science.gov (United States)

    Wessel, Jan R; Ullsperger, Markus

    2011-02-01

    Following the development of increasingly precise measurement instruments and fine-grain analysis tools for electroencephalographic (EEG) data, analysis of single-trial event-related EEG has considerably widened the utility of this non-invasive method to investigate brain activity. Recently, independent component analysis (ICA) has become one of the most prominent techniques for increasing the feasibility of single-trial EEG. This blind source separation technique extracts statistically independent components (ICs) from the EEG raw signal. By restricting the signal analysis to those ICs representing the processes of interest, single-trial analysis becomes more flexible. Still, the selection-criteria for in- or exclusion of certain ICs are largely subjective and unstandardized, as is the actual selection process itself. We present a rationale for a bottom-up, data-driven IC selection approach, using clear-cut inferential statistics on both temporal and spatial information to identify components that significantly contribute to a certain event-related brain potential (ERP). With time-range being the only necessary input, this approach considerably reduces the pre-assumptions for IC selection and promotes greater objectivity of the selection process itself. To test the validity of the approach presented here, we present results from a simulation and re-analyze data from a previously published ERP experiment on error processing. We compare the ERP-based IC selections made by our approach to the selection made based on mere signal power. The comparison of ERP integrity, signal-to-noise ratio, and single-trial properties of the back-projected ICs outlines the validity of the approach presented here. In addition, functional validity of the extracted error-related EEG signal is tested by investigating whether it is predictive for subsequent behavioural adjustments. Copyright © 2010 Elsevier Inc. All rights reserved.

  19. Studying brain organization via spontaneous fMRI signal.

    Science.gov (United States)

    Power, Jonathan D; Schlaggar, Bradley L; Petersen, Steven E

    2014-11-19

    In recent years, some substantial advances in understanding human (and nonhuman) brain organization have emerged from a relatively unusual approach: the observation of spontaneous activity, and correlated patterns in spontaneous activity, in the "resting" brain. Most commonly, spontaneous neural activity is measured indirectly via fMRI signal in subjects who are lying quietly in the scanner, the so-called "resting state." This Primer introduces the fMRI-based study of spontaneous brain activity, some of the methodological issues active in the field, and some ways in which resting-state fMRI has been used to delineate aspects of area-level and supra-areal brain organization. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Signalling properties of inorganic polyphosphate in the mammalian brain.

    Science.gov (United States)

    Holmström, Kira M; Marina, Nephtali; Baev, Artyom Y; Wood, Nicholas W; Gourine, Alexander V; Abramov, Andrey Y

    2013-01-01

    Inorganic polyphosphate is known to be present in the mammalian brain at micromolar concentrations. Here we show that polyphosphate may act as a gliotransmitter, mediating communication between astrocytes. It is released by astrocytes in a calcium-dependent manner and signals to neighbouring astrocytes through P2Y(1) purinergic receptors, activation of phospholipase C and release of calcium from the intracellular stores. In primary neuroglial cultures, application of polyP triggers release of endogenous polyphosphate from astrocytes while neurons take it up. In vivo, central actions of polyphosphate at the level of the brainstem include profound increases in key homeostatic physiological activities, such as breathing, central sympathetic outflow and the arterial blood pressure. Together, these results suggest a role for polyphosphate as a mediator of astroglial signal transmission in the mammalian brain.

  1. ASPM regulates Wnt signaling pathway activity in the developing brain.

    Science.gov (United States)

    Buchman, Joshua J; Durak, Omer; Tsai, Li-Huei

    2011-09-15

    Autosomal recessive primary microcephaly (MCPH) is a neural developmental disorder in which patients display significantly reduced brain size. Mutations in Abnormal Spindle Microcephaly (ASPM) are the most common cause of MCPH. Here, we investigate the underlying functions of Aspm in brain development and find that Aspm expression is critical for proper neurogenesis and neuronal migration. The Wnt signaling pathway is known for its roles in embryogenesis, and genome-wide siRNA screens indicate that ASPM is a positive regulator of Wnt signaling. We demonstrate that knockdown of Aspm results in decreased Wnt-mediated transcription, and that expression of stabilized β-catenin can rescue this deficit. Finally, coexpression of stabilized β-catenin can rescue defects observed upon in vivo knockdown of Aspm. Our findings provide an impetus to further explore Aspm's role in facilitating Wnt-mediated neurogenesis programs, which may contribute to psychiatric illness etiology when perturbed.

  2. Electroencephalogram signals processing for topographic brain mapping and epilepsies classification.

    Science.gov (United States)

    Arab, Mohammad Reza; Suratgar, Amir Abolfazl; Ashtiani, Alireza Rezaei

    2010-09-01

    In this study, topographic brain mapping and wavelet transform-neural network method are used for the classification of grand mal (clonic stage) and petit mal (absence) epilepsies into healthy, ictal and interictal (EEGs). Preprocessing is included to remove artifacts occurred by blinking, wandering baseline (electrodes movement) and eyeball movement using the Discrete Wavelet Transformation (DWT). De-noising EEG signals from the AC power supply frequency with a suitable notch filter is another job of preprocessing. In experimental data, the preprocessing enhanced speed and accuracy of the processing stage (wavelet transform and neural network). The EEGs signals are categorized to normal and petit mal and clonic epilepsy by an expert neurologist. The categorization is confirmed by Fast Fourier Transform (FFT) analysis and brain mapping. The dataset includes waves such as sharp, spike and spike-slow wave. Through the Counties Wavelet Transform (CWT) of EEG records, transient features are accurately captured and separated and used as classifier input. We introduce a two-stage classifier based on the Learning Vector Quantization (LVQ) neural network location in both time and frequency contexts. The brain mapping used for finding the epilepsy locates in the brain. The simulation results are very promising and the accuracy of the proposed classifier in experimental clinical data is ∼80%. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Signals from the brain induce variation in avian facial shape.

    Science.gov (United States)

    Hu, Diane; Young, Nathan M; Xu, Qiuping; Jamniczky, Heather; Green, Rebecca M; Mio, Washington; Marcucio, Ralph S; Hallgrimsson, Benedikt

    2015-04-22

    How developmental mechanisms generate the phenotypic variation that is the raw material for evolution is largely unknown. Here, we explore whether variation in a conserved signaling axis between the brain and face contributes to differences in morphogenesis of the avian upper jaw. In amniotes, including both mice and avians, signals from the brain establish a signaling center in the ectoderm (the Frontonasal ectodermal zone or "FEZ") that directs outgrowth of the facial primordia. Here we show that the spatial organization of this signaling center differs among avians, and these correspond to Sonic hedgehog (Shh) expression in the basal forebrain and embryonic facial shape. In ducks this basal forebrain domain is present almost the entire width, while in chickens it is restricted to the midline. When the duck forebrain is unilaterally transplanted into stage matched chicken embryos the face on the treated side resembles that of the donor. Combined with previous findings, these results demonstrate that variation in a highly conserved developmental pathway has the potential to contribute to evolutionary differences in avian upper jaw morphology. Developmental Dynamics, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  4. Nuclear calcium signalling in the regulation of brain function.

    Science.gov (United States)

    Bading, Hilmar

    2013-09-01

    Synaptic activity initiates biochemical processes that have various outcomes, including the formation of memories, increases in neuronal survival and the development of chronic pain and addiction. Virtually all activity-induced, long-lasting adaptations of brain functions require a dialogue between synapses and the nucleus that results in changes in gene expression. Calcium signals that are induced by synaptic activity and propagate into the nucleus are a major route for synapse-to-nucleus communication. Recent findings indicate that diverse forms of neuroadaptation require calcium transients in the nucleus to switch on the necessary genomic programme. Deficits in nuclear calcium signalling as a result of a reduction in synaptic activity or increased extrasynaptic NMDA receptor signalling may underlie the aetiologies of various diseases, including neurodegeneration and cognitive dysfunction.

  5. Brain-computer interfaces increase whole-brain signal to noise.

    Science.gov (United States)

    Papageorgiou, T Dorina; Lisinski, Jonathan M; McHenry, Monica A; White, Jason P; LaConte, Stephen M

    2013-08-13

    Brain-computer interfaces (BCIs) can convert mental states into signals to drive real-world devices, but it is not known if a given covert task is the same when performed with and without BCI-based control. Using a BCI likely involves additional cognitive processes, such as multitasking, attention, and conflict monitoring. In addition, it is challenging to measure the quality of covert task performance. We used whole-brain classifier-based real-time functional MRI to address these issues, because the method provides both classifier-based maps to examine the neural requirements of BCI and classification accuracy to quantify the quality of task performance. Subjects performed a covert counting task at fast and slow rates to control a visual interface. Compared with the same task when viewing but not controlling the interface, we observed that being in control of a BCI improved task classification of fast and slow counting states. Additional BCI control increased subjects' whole-brain signal-to-noise ratio compared with the absence of control. The neural pattern for control consisted of a positive network comprised of dorsal parietal and frontal regions and the anterior insula of the right hemisphere as well as an expansive negative network of regions. These findings suggest that real-time functional MRI can serve as a platform for exploring information processing and frontoparietal and insula network-based regulation of whole-brain task signal-to-noise ratio.

  6. Signal vs. Noise: Obtaining a representative δ18O record in a low-accumulation region

    Science.gov (United States)

    Münch, Thomas; Kipfstuhl, Sepp; Freitag, Johannes; Meyer, Hanno; Laepple, Thomas

    2015-04-01

    Single ice cores have been proven to be a key archive to reconstruct climate changes on glacial to interglacial time scales in temperature as well as in greenhouse gases and many other climate parameters. In contrast, for the Holocene climate evolution single ice cores are likely less reliable recorders. The small amplitude of Holocene climate changes, together with the goal to reconstruct high-temporal resolution records down to subannual timescales, poses a significant challenge to the interpretation of ice core signals, especially in low-accumulation regions as the Antarctic plateau. In order to learn about the representativity of single firn cores and to optimize future ice-core based climate reconstructions, we undertook an extensive study of replicate firn coring and surface snow sampling at Kohnen station on Dronning Maud Land, Antarctica. For the first time - to our knowledge - two-dimensional images of the water isotope and density structure of the upper firn have been obtained from two 45 m long and 1.2 m deep firn trenches separated at a distance of 500 m, yielding a climate proxy archive spanning roughly the last five years. In this contribution, we present the results of the stable water isotope compositions obtained from the two firn trenches. Seasonal layering of the isotopes is following an absolute depth scale likely caused by an annual reorganization of the snow surface directly related to the local dune scale. Local surface winds cause highly variable isotopic signals of the surface snow, featuring a similar range as the seasonal cycle. However, even in deeper layers, strong perturbations of the isotopic stratigraphy are found, resulting in a low representativity of single firn cores. On the contrary, the mean trench profiles are highly correlated, giving a representative climate signal over a spatial scale of at least 500 m. The decorrelation length of the stratigraphic noise is ~10 m, yielding an estimate of an optimal sampling strategy for

  7. Analyzing brain signals using decision trees: an approach based on neuroscience

    OpenAIRE

    Diana Francisca Adamatti; Josimara Silveira; Fernanda de Carvalho

    2016-01-01

    This paper presents a case study of treatment of brain signals using decision trees to classify of these signals, and they are analyzed based on neuroscience. We have collected brain signals for 3 subjects during an imagination task and we classify these signals using decision trees, a supervised machine learning method. To analyze the processing data and basing in neuroscience, we have defined a matching between the electrodes position and the corresponding functions into brain. The results ...

  8. The arterial circle of the brain, its branches and connections in selected representatives of the Antilopinae.

    Science.gov (United States)

    Frąckowiak, Hieronim; Dębiński, Dariusz; Komosa, Marcin; Zdun, Maciej

    2015-07-01

    The arterial circle of the brain, that is, the circle of Willis, and its branches in ruminants have been chiefly described in farm animals and only in selected wild species. In view of the deficit of information about this vascular region in numerous other species of the Ruminantia, the arteries of the encephalic base were analyzed in five antelope species representing different genera of the Bovidae, Antilopinae. Specimens of the following species were examined: springbuck (Antidorcas marsupialis), blackbuck (Antilope cervicapra), dik-dik (Madoqua kirkii), saiga (Saiga tatarica), and oribi (Ourebia ourebi). Post-autopsy material received from domestic zoological gardens was used to inject the bilateral common carotid arteries with a stained acetone solution of vinyl superchloride. When the material was polymerized, the specimens were macerated enzymatically. The process resulted in casts of arteries of the head and encephalic base on a skeletal scaffold. The investigations revealed that the bilateral components of the arterial circle of the brain, that is, the rostral cerebral artery and caudal communicating artery, arose from the division of the intracranial segment of the internal carotid artery, which emerges from the rostral epidural rete mirabile. The extracranial segment of the internal carotid artery was obliterated. In consequence of this process, the blood reaches the brain chiefly from the maxillary artery. The research proved that the arteries of the encephalic base in the Antilopinae are most similar to the vessels described in antelopes of Tragelaphus, Taurotragus, and Boselaphus genera and small domestic ruminants. However, they are different from the arterial pattern of the encephalic base in bovines and other species classified as the Bovini. © 2015 Wiley Periodicals, Inc.

  9. Somatic and vicarious pain are represented by dissociable multivariate brain patterns

    Science.gov (United States)

    Krishnan, Anjali; Woo, Choong-Wan; Chang, Luke J; Ruzic, Luka; Gu, Xiaosi; López-Solà, Marina; Jackson, Philip L; Pujol, Jesús; Fan, Jin; Wager, Tor D

    2016-01-01

    Understanding how humans represent others’ pain is critical for understanding pro-social behavior. ‘Shared experience’ theories propose common brain representations for somatic and vicarious pain, but other evidence suggests that specialized circuits are required to experience others’ suffering. Combining functional neuroimaging with multivariate pattern analyses, we identified dissociable patterns that predicted somatic (high versus low: 100%) and vicarious (high versus low: 100%) pain intensity in out-of-sample individuals. Critically, each pattern was at chance in predicting the other experience, demonstrating separate modifiability of both patterns. Somatotopy (upper versus lower limb: 93% accuracy for both conditions) was also distinct, located in somatosensory versus mentalizing-related circuits for somatic and vicarious pain, respectively. Two additional studies demonstrated the generalizability of the somatic pain pattern (which was originally developed on thermal pain) to mechanical and electrical pain, and also demonstrated the replicability of the somatic/vicarious dissociation. These findings suggest possible mechanisms underlying limitations in feeling others’ pain, and present new, more specific, brain targets for studying pain empathy. DOI: http://dx.doi.org/10.7554/eLife.15166.001 PMID:27296895

  10. Dissociable Effects on Birdsong of Androgen Signaling in Cortex-Like Brain Regions of Canaries.

    Science.gov (United States)

    Alward, Beau A; Balthazart, Jacques; Ball, Gregory F

    2017-09-06

    The neural basis of how learned vocalizations change during development and in adulthood represents a major challenge facing cognitive neuroscience. This plasticity in the degree to which learned vocalizations can change in both humans and songbirds is linked to the actions of sex steroid hormones during ontogeny but also in adulthood in the context of seasonal changes in birdsong. We investigated the role of steroid hormone signaling in the brain on distinct features of birdsong using adult male canaries (Serinus canaria), which show extensive seasonal vocal plasticity as adults. Specifically, we bilaterally implanted the potent androgen receptor antagonist flutamide in two key brain regions that control birdsong. We show that androgen signaling in the motor cortical-like brain region, the robust nucleus of the arcopallium (RA), controls syllable and trill bandwidth stereotypy, while not significantly affecting higher order features of song such syllable-type usage (i.e., how many times each syllable type is used) or syllable sequences. In contrast, androgen signaling in the premotor cortical-like brain region, HVC (proper name), controls song variability by increasing the variability of syllable-type usage and syllable sequences, while having no effect on syllable or trill bandwidth stereotypy. Other aspects of song, such as the duration of trills and the number of syllables per song, were also differentially affected by androgen signaling in HVC versus RA. These results implicate androgens in regulating distinct features of complex motor output in a precise and nonredundant manner.SIGNIFICANCE STATEMENT Vocal plasticity is linked to the actions of sex steroid hormones, but the precise mechanisms are unclear. We investigated this question in adult male canaries (Serinus canaria), which show extensive vocal plasticity throughout their life. We show that androgens in two cortex-like vocal control brain regions regulate distinct aspects of vocal plasticity. For

  11. Optical mapping of the dominant frequency of brain signal oscillations in motor systems.

    Science.gov (United States)

    Lu, Feng-Mei; Wang, Yi-Feng; Zhang, Juan; Chen, Hua-Fu; Yuan, Zhen

    2017-11-07

    Recent neuroimaging studies revealed that the dominant frequency of neural oscillations is brain-region-specific and can vary with frequency-specific reorganization of brain networks during cognition. In this study, we examined the dominant frequency in low-frequency neural oscillations represented by oxygenated hemoglobin measurements after the hemodynamic response function (HRF) deconvolution. Twenty-nine healthy college subjects were recruited to perform a serial finger tapping task at the frequency of 0.2 Hz. Functional near-infrared spectroscopy (fNIRS) was applied to record the hemodynamic signals over the primary motor cortex, supplementary motor area (SMA), premotor cortex, and prefrontal area. We then explored the low frequency steady-state brain response (lfSSBR), which was evoked in the motor systems at the fundamental frequency (0.2 Hz) and its harmonics (0.4, 0.6, and 0.8 Hz). In particular, after HRF deconvolution, the lfSSBR at the frequency of 0.4 Hz in the SMA was identified as the dominant frequency. Interestingly, the domain frequency exhibited the correlation with behavior data such as reaction time, indicating that the physiological implication of lfSSBR is related to the brain anatomy, stimulus frequency and cognition. More importantly, the HRF deconvolution showed its capability for recovering signals probably reflecting neural-level events and revealing the physiological meaning of lfSSBR.

  12. Reduced Predictable Information in Brain Signals in Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Carlos eGomez

    2014-02-01

    Full Text Available Autism spectrum disorder (ASD is a common developmental disorder characterized by communication difficulties and impaired social interaction. Recent results suggest altered brain dynamics as a potential cause of symptoms in ASD. Here, we aim to describe potential information-processing consequences of these alterations by measuring active information storage (AIS – a key quantity in the theory of distributed computation in biological networks. AIS is defined as the mutual information between the semi-infinite past of a process and its next state. It measures the amount of stored information that is used for computation of the next time step of a process. AIS is high for rich but predictable dynamics. We recorded magnetoencephalography (MEG signals in 13 ASD patients and 14 matched control subjects in a visual task. After a beamformer source analysis, twelve task-relevant sources were obtained. For these sources, stationary baseline activity was analyzed using AIS. Our results showed a decrease of AIS values in the hippocampus of ASD patients in comparison with controls, meaning that brain signals in ASD were either less predictable, reduced in their dynamic richness or both. Our study suggests the usefulness of AIS to detect an abnormal type of dynamics in ASD. The observed changes in AIS are compatible with Bayesian theories of reduced use or precision of priors in ASD.

  13. Reduced predictable information in brain signals in autism spectrum disorder

    Science.gov (United States)

    Gómez, Carlos; Lizier, Joseph T.; Schaum, Michael; Wollstadt, Patricia; Grützner, Christine; Uhlhaas, Peter; Freitag, Christine M.; Schlitt, Sabine; Bölte, Sven; Hornero, Roberto; Wibral, Michael

    2014-01-01

    Autism spectrum disorder (ASD) is a common developmental disorder characterized by communication difficulties and impaired social interaction. Recent results suggest altered brain dynamics as a potential cause of symptoms in ASD. Here, we aim to describe potential information-processing consequences of these alterations by measuring active information storage (AIS)—a key quantity in the theory of distributed computation in biological networks. AIS is defined as the mutual information between the past state of a process and its next measurement. It measures the amount of stored information that is used for computation of the next time step of a process. AIS is high for rich but predictable dynamics. We recorded magnetoencephalography (MEG) signals in 10 ASD patients and 14 matched control subjects in a visual task. After a beamformer source analysis, 12 task-relevant sources were obtained. For these sources, stationary baseline activity was analyzed using AIS. Our results showed a decrease of AIS values in the hippocampus of ASD patients in comparison with controls, meaning that brain signals in ASD were either less predictable, reduced in their dynamic richness or both. Our study suggests the usefulness of AIS to detect an abnormal type of dynamics in ASD. The observed changes in AIS are compatible with Bayesian theories of reduced use or precision of priors in ASD. PMID:24592235

  14. TGF-beta signaling specifies axons during brain development.

    Science.gov (United States)

    Yi, Jason J; Barnes, Anthony P; Hand, Randal; Polleux, Franck; Ehlers, Michael D

    2010-07-09

    In the mammalian brain, the specification of a single axon and multiple dendrites occurs early in the differentiation of most neuron types. Numerous intracellular signaling events for axon specification have been described in detail. However, the identity of the extracellular factor(s) that initiate neuronal polarity in vivo is unknown. Here, we report that transforming growth factor beta (TGF-beta) initiates signaling pathways both in vivo and in vitro to fate naive neurites into axons. Neocortical neurons lacking the type II TGF-beta receptor (TbetaR2) fail to initiate axons during development. Exogenous TGF-beta is sufficient to direct the rapid growth and differentiation of an axon, and genetic enhancement of receptor activity promotes the formation of multiple axons. Finally, we show that the bulk of these TGF-beta-dependent events are mediated by site-specific phosphorylation of Par6. These results define an extrinsic cue for neuronal polarity in vivo that patterns neural circuits in the developing brain. Copyright 2010 Elsevier Inc. All rights reserved.

  15. EGFR and HER2 signaling in breast cancer brain metastasis

    Science.gov (United States)

    Sirkisoon, Sherona R.; Carpenter, Richard L.; Rimkus, Tadas; Miller, Lance; Metheny-Barlow, Linda; Lo, Hui-Wen

    2016-01-01

    Breast cancer occurs in approximately 1 in 8 women and 1 in 37 women with breast cancer succumbed to the disease. Over the past decades, new diagnostic tools and treatments have substantially improved the prognosis of women with local diseases. However, women with metastatic disease still have a dismal prognosis without effective treatments. Among different molecular subtypes of breast cancer, the HER2-enriched and basal-like subtypes typically have higher rates of metastasis to the brain. Basal-like metastatic breast tumors frequently express EGFR. Consequently, HER2- and EGFR-targeted therapies are being used in the clinic and/or evaluated in clinical trials for treating breast cancer patients with brain metastases. In this review, we will first provide an overview of the HER2 and EGFR signaling pathways. The roles that EGFR and HER2 play in breast cancer metastasis to the brain will then be discussed. Finally, we will summarize the preclinical and clinical effects of EGFR- and HER2-targeted therapies on breast cancer metastasis. PMID:26709660

  16. Accumulated Source Imaging of Brain Activity with Both Low and High-Frequency Neuromagnetic Signals

    Directory of Open Access Journals (Sweden)

    Jing eXiang

    2014-05-01

    Full Text Available Recent studies have revealed the importance of high-frequency brain signals (>70 Hz. One challenge of high-frequency signal analysis is that the size of time-frequency representation of high-frequency brain signals could be larger than 1 terabytes (TB, which is beyond the upper limits of a typical computer workstation’s memory (<196 GB. The aim of the present study is to develop a new method to provide greater sensitivity in detecting high-frequency magnetoencephalography (MEG signals in a single automated and versatile interface, rather than the more traditional, time-intensive visual inspection methods, which may take up to several days. To address the aim, we developed a new method, accumulated source imaging, defined as the volumetric summation of source activity over a period of time. This method analyzes signals in both low- (1~70 Hz and high-frequency (70~200 Hz ranges at source levels. To extract meaningful information from MEG signals at sensor space, the signals were decomposed to channel-cross-channel matrix (CxC representing the spatiotemporal patterns of every possible sensor-pair. A new algorithm was developed and tested by calculating the optimal CxC and source location-orientation weights for volumetric source imaging, thereby minimizing multi-source interference and reducing computational cost. The new method was implemented in C/C++ and tested with MEG data recorded from clinical epilepsy patients. The results of experimental data demonstrated that accumulated source imaging could effectively summarize and visualize MEG recordings within 12.7 hours by using approximately 10 GB of computer memory. In contrast to the conventional method of visually identifying multi-frequency epileptic activities that traditionally took 2-3 days and used 1-2 TB storage, the new approach can quantify epileptic abnormalities in both low- and high-frequency ranges at source levels, using much less time and computer memory.

  17. Adipocyte glucocorticoid receptors mediate fat-to-brain signaling.

    Science.gov (United States)

    de Kloet, Annette D; Krause, Eric G; Solomon, Matia B; Flak, Jonathan N; Scott, Karen A; Kim, Dong-Hoon; Myers, Brent; Ulrich-Lai, Yvonne M; Woods, Stephen C; Seeley, Randy J; Herman, James P

    2015-06-01

    Stress-related (e.g., depression) and metabolic pathologies (e.g., obesity) are important and often co-morbid public health concerns. Here we identify a connection between peripheral glucocorticoid receptor (GR) signaling originating in fat with the brain control of both stress and metabolism. Mice with reduced adipocyte GR hypersecrete glucocorticoids following acute psychogenic stress and are resistant to diet-induced obesity. This hypersecretion gives rise to deficits in responsiveness to exogenous glucocorticoids, consistent with reduced negative feedback via adipocytes. Increased stress reactivity occurs in the context of elevated hypothalamic expression of hypothalamic-pituitary-adrenal (HPA) axis-excitatory neuropeptides and in the absence of altered adrenal sensitivity, consistent with a central cite of action. Our results identify a novel mechanism whereby activation of the adipocyte GR promotes peripheral energy storage while inhibiting the HPA axis, and provide functional evidence for a fat-to-brain regulatory feedback network that serves to regulate not just homeostatic energy balance but also responses to psychogenic stimuli. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. The gender of face stimuli is represented in multiple regions in the human brain

    Directory of Open Access Journals (Sweden)

    Christian eKaul

    2011-01-01

    Full Text Available Face perception in humans is mediated by activation in a network of brain areas. Conventionalunivariate fMRI data analysis has not localized differential responses to viewing male ascompared with viewing female faces within this network. We tested whether we could detectneural response patterns specific to viewing male vs. female faces in forty participants.Replicating earlier work, face stimuli evoked activation in the core (inferior occipital gyrus(IOG, fusiform gyrus (FG and superior temporal sulcus (STS, as well as extended(amygdala, inferior frontal gyrus (IFG, insula (INS, and orbitofrontal cortex (OFC regionsof the face network. Multivariate pattern classification of activity within these regions revealedsuccessful decoding of gender information, significantly above chance, in the IOG, FG, STS,IFG, INS and OFC, but not in the amygdala. Multiple control regions indicated that this resultmight be restricted to face-responsive regions. Our findings suggest that gender information isdistributed across the face network and is represented in the core regions that process invariantfacial features, as well as the extended regions that process changeable aspects of faces.

  19. Biophoton signal transmission and processing in the brain.

    Science.gov (United States)

    Tang, Rendong; Dai, Jiapei

    2014-10-05

    The transmission and processing of neural information in the nervous system plays a key role in neural functions. It is well accepted that neural communication is mediated by bioelectricity and chemical molecules via the processes called bioelectrical and chemical transmission, respectively. Indeed, the traditional theories seem to give valuable explanations for the basic functions of the nervous system, but difficult to construct general accepted concepts or principles to provide reasonable explanations of higher brain functions and mental activities, such as perception, learning and memory, emotion and consciousness. Therefore, many unanswered questions and debates over the neural encoding and mechanisms of neuronal networks remain. Cell to cell communication by biophotons, also called ultra-weak photon emissions, has been demonstrated in several plants, bacteria and certain animal cells. Recently, both experimental evidence and theoretical speculation have suggested that biophotons may play a potential role in neural signal transmission and processing, contributing to the understanding of the high functions of nervous system. In this paper, we review the relevant experimental findings and discuss the possible underlying mechanisms of biophoton signal transmission and processing in the nervous system. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Somatic and vicarious pain are represented by dissociable multivariate brain patterns

    National Research Council Canada - National Science Library

    Krishnan, Anjali; Woo, Choong-Wan; Chang, Luke J; Ruzic, Luka; Gu, Xiaosi; López-Solà, Marina; Jackson, Philip L; Pujol, Jesús; Fan, Jin; Wager, Tor D

    2016-01-01

    .... 'Shared experience' theories propose common brain representations for somatic and vicarious pain, but other evidence suggests that specialized circuits are required to experience others' suffering...

  1. Notch-1 Signalling Is Activated in Brain Arteriovenous Malformations in Humans

    Science.gov (United States)

    ZhuGe, Qichuan; Zhong, Ming; Zheng, WeiMing; Yang, Guo-Yuan; Mao, XiaoOu; Xie, Lin; Chen, Gourong; Chen, Yongmei; Lawton, Michael T.; Young, William L.; Greenberg, David A.; Jin, Kunlin

    2009-01-01

    A role for the Notch signalling pathway in the formation of arteriovenous malformations during development has been suggested. However, whether Notch signalling is involved in brain arteriovenous malformations in humans remains unclear. Here, we performed immunohistochemistry on surgically resected brain arteriovenous malformations and found that,…

  2. From EEG signals to brain connectivity: a model-based evaluation of interdependence measures.

    Science.gov (United States)

    Wendling, Fabrice; Ansari-Asl, Karim; Bartolomei, Fabrice; Senhadji, Lotfi

    2009-09-30

    In the past, considerable effort has been devoted to the development of signal processing techniques aimed at characterizing brain connectivity from signals recorded from spatially-distributed regions during normal or pathological conditions. In this paper, three families of methods (linear and nonlinear regression, phase synchronization, and generalized synchronization) are reviewed. Their performances were evaluated according to a model-based methodology in which a priori knowledge about the underlying relationship between systems that generate output signals is available. This approach allowed us to relate the interdependence measures computed by connectivity methods to the actual values of the coupling parameter explicitly represented in various models of signal generation. Results showed that: (i) some of the methods were insensitive to the coupling parameter; (ii) results were dependent on signal properties (broad band versus narrow band); (iii) there was no "ideal" method, i.e., none of the methods performed better than the other ones in all studied situations. Nevertheless, regression methods showed sensitivity to the coupling parameter in all tested models with average or good performances. Therefore, it is advised to first apply these "robust" methods in order to characterize brain connectivity before using more sophisticated methods that require specific assumptions about the underlying model of relationship. In all cases, it is recommended to compare the results obtained from different connectivity methods to get more reliable interpretation of measured quantities with respect to underlying coupling. In addition, time-frequency methods are also recommended when coupling in specific frequency sub-bands ("frequency-locking") is likely to occur as in epilepsy.

  3. Automated EEG signal analysis for identification of epilepsy seizures and brain tumour.

    Science.gov (United States)

    Sharanreddy, M; Kulkarni, P K

    2013-11-01

    Abstract Electroencephalography (EEG) is a clinical test which records neuro-electrical activities generated by brain structures. EEG test results used to monitor brain diseases such as epilepsy seizure, brain tumours, toxic encephalopathies infections and cerebrovascular disorders. Due to the extreme variation in the EEG morphologies, manual analysis of the EEG signal is laborious, time consuming and requires skilled interpreters, who by the nature of the task are prone to subjective judegment and error. Further, manual analysis of the EEG results often fails to detect and uncover subtle features. This paper proposes an automated EEG analysis method by combining digital signal processing and neural network techniques, which will remove error and subjectivity associated with manual analysis and identifies the existence of epilepsy seizure and brain tumour diseases. The system uses multi-wavelet transform for feature extraction in which an input EEG signal is decomposed in a sub-signal. Irregularities and unpredictable fluctuations present in the decomposed signal are measured using approximate entropy. A feed-forward neural network is used to classify the EEG signal as a normal, epilepsy or brain tumour signal. The proposed technique is implemented and tested on data of 500 EEG signals for each disease. Results are promising, with classification accuracy of 98% for normal, 93% for epilepsy and 87% for brain tumour. Along with classification, the paper also highlights the EEG abnormalities associated with brain tumour and epilepsy seizure.

  4. Multi-Scale Factor Analysis of High-Dimensional Brain Signals

    KAUST Repository

    Ting, Chee-Ming

    2017-05-18

    In this paper, we develop an approach to modeling high-dimensional networks with a large number of nodes arranged in a hierarchical and modular structure. We propose a novel multi-scale factor analysis (MSFA) model which partitions the massive spatio-temporal data defined over the complex networks into a finite set of regional clusters. To achieve further dimension reduction, we represent the signals in each cluster by a small number of latent factors. The correlation matrix for all nodes in the network are approximated by lower-dimensional sub-structures derived from the cluster-specific factors. To estimate regional connectivity between numerous nodes (within each cluster), we apply principal components analysis (PCA) to produce factors which are derived as the optimal reconstruction of the observed signals under the squared loss. Then, we estimate global connectivity (between clusters or sub-networks) based on the factors across regions using the RV-coefficient as the cross-dependence measure. This gives a reliable and computationally efficient multi-scale analysis of both regional and global dependencies of the large networks. The proposed novel approach is applied to estimate brain connectivity networks using functional magnetic resonance imaging (fMRI) data. Results on resting-state fMRI reveal interesting modular and hierarchical organization of human brain networks during rest.

  5. Expression profiling of autism candidate genes during human brain development implicates central immune signaling pathways.

    Directory of Open Access Journals (Sweden)

    Mark N Ziats

    Full Text Available The Autism Spectrum Disorders (ASD represent a clinically heterogeneous set of conditions with strong hereditary components. Despite substantial efforts to uncover the genetic basis of ASD, the genomic etiology appears complex and a clear understanding of the molecular mechanisms underlying Autism remains elusive. We hypothesized that focusing gene interaction networks on ASD-implicated genes that are highly expressed in the developing brain may reveal core mechanisms that are otherwise obscured by the genomic heterogeneity of the disorder. Here we report an in silico study of the gene expression profile from ASD-implicated genes in the unaffected developing human brain. By implementing a biologically relevant approach, we identified a subset of highly expressed ASD-candidate genes from which interactome networks were derived. Strikingly, immune signaling through NFκB, Tnf, and Jnk was central to ASD networks at multiple levels of our analysis, and cell-type specific expression suggested glia--in addition to neurons--deserve consideration. This work provides integrated genomic evidence that ASD-implicated genes may converge on central cytokine signaling pathways.

  6. Expression profiling of autism candidate genes during human brain development implicates central immune signaling pathways.

    Science.gov (United States)

    Ziats, Mark N; Rennert, Owen M

    2011-01-01

    The Autism Spectrum Disorders (ASD) represent a clinically heterogeneous set of conditions with strong hereditary components. Despite substantial efforts to uncover the genetic basis of ASD, the genomic etiology appears complex and a clear understanding of the molecular mechanisms underlying Autism remains elusive. We hypothesized that focusing gene interaction networks on ASD-implicated genes that are highly expressed in the developing brain may reveal core mechanisms that are otherwise obscured by the genomic heterogeneity of the disorder. Here we report an in silico study of the gene expression profile from ASD-implicated genes in the unaffected developing human brain. By implementing a biologically relevant approach, we identified a subset of highly expressed ASD-candidate genes from which interactome networks were derived. Strikingly, immune signaling through NFκB, Tnf, and Jnk was central to ASD networks at multiple levels of our analysis, and cell-type specific expression suggested glia--in addition to neurons--deserve consideration. This work provides integrated genomic evidence that ASD-implicated genes may converge on central cytokine signaling pathways.

  7. Sources and implications of whole-brain fMRI signals in humans.

    Science.gov (United States)

    Power, Jonathan D; Plitt, Mark; Laumann, Timothy O; Martin, Alex

    2017-02-01

    Whole-brain fMRI signals are a subject of intense interest: variance in the global fMRI signal (the spatial mean of all signals in the brain) indexes subject arousal, and psychiatric conditions such as schizophrenia and autism have been characterized by differences in the global fMRI signal. Further, vigorous debates exist on whether global signals ought to be removed from fMRI data. However, surprisingly little research has focused on the empirical properties of whole-brain fMRI signals. Here we map the spatial and temporal properties of the global signal, individually, in 1000+ fMRI scans. Variance in the global fMRI signal is strongly linked to head motion, to hardware artifacts, and to respiratory patterns and their attendant physiologic changes. Many techniques used to prepare fMRI data for analysis fail to remove these uninteresting kinds of global signal fluctuations. Thus, many studies include, at the time of analysis, prominent global effects of yawns, breathing changes, and head motion, among other signals. Such artifacts will mimic dynamic neural activity and will spuriously alter signal covariance throughout the brain. Methods capable of isolating and removing global artifactual variance while preserving putative "neural" variance are needed; this paper adopts no position on the topic of global signal regression. Published by Elsevier Inc.

  8. Dopamine regulates two classes of primate prefrontal neurons that represent sensory signals.

    Science.gov (United States)

    Jacob, Simon N; Ott, Torben; Nieder, Andreas

    2013-08-21

    The lateral prefrontal cortex (PFC), a hub of higher-level cognitive processing, is strongly modulated by midbrain dopamine (DA) neurons. The cellular mechanisms have been comprehensively studied in the context of short-term memory, but little is known about how DA regulates sensory inputs to PFC that precede and give rise to such memory activity. By preparing recipient cortical circuits for incoming signals, DA could be a powerful determinant of downstream cognitive processing. Here, we tested the hypothesis that prefrontal DA regulates the representation of sensory signals that are required for perceptual decisions. In rhesus monkeys trained to report the presence or absence of visual stimuli at varying levels of contrast, we simultaneously recorded extracellular single-unit activity and applied DA to the immediate vicinity of the neurons by micro-iontophoresis. We found that DA modulation of prefrontal neurons is not uniform but tailored to specialized neuronal classes. In one population of neurons, DA suppressed activity with high temporal precision but preserved signal/noise ratio. Neurons in this group had short visual response latencies and comprised all recorded narrow-spiking, putative interneurons. In a distinct population, DA increased excitability and enhanced signal/noise ratio by reducing response variability. These neurons had longer visual response latencies and were composed exclusively of broad-spiking, putative pyramidal neurons. By gating sensory inputs to PFC and subsequently strengthening the representation of sensory signals, DA might play an important role in shaping how the PFC initiates appropriate behavior in response to changes in the sensory environment.

  9. Brain-Region Specific Apoptosis Triggered by Eph/ephrin Signaling.

    Science.gov (United States)

    Park, Soochul

    2013-09-01

    Eph receptors and their ligands, ephrins, are abundantly expressed in neuroepithelial cells of the early embryonic brain. Overstimulation of Eph signaling in vivo increases apoptotic cell death of neuroepithelial cells, whereas null mutation of the Eph gene leads to the development of a larger brain during embryogenesis. Thus, it appears that Eph-ephrin signaling plays a role in regulating apoptotic cell death of neuroepithelial cells, thereby influencing brain size during embryonic development. Interestingly, Eph-ephrin signaling is bi-directional, with forward signaling from ephrin- to Eph-expressing cells and reverse signaling from Eph- to ephrin-expressing cells. However, it is not clear whether this forward or reverse signaling plays a role in regulating the size of the neuroepithelial cell population during early brain development. Also, Eph receptors and their corresponding ligands are mutually exclusive in their expression domains, and they encounter each other only at interfaces between their expression domains. This expression pattern may be a critical mechanism for preventing overstimulation of Eph-ephrin signaling. Nevertheless, Eph receptors are co-expressed with their corresponding ligands in certain brain regions. Recently, two studies demonstrated that brain region-specific apoptosis may be triggered by the overlapping expression of Eph and ephrin, a theme that will be explored in this mini-review.

  10. A New Method to Represent Speech Signals Via Predefined Signature and Envelope Sequences

    Directory of Open Access Journals (Sweden)

    Binboga Sıddık Yarman

    2007-01-01

    Full Text Available A novel systematic procedure referred to as “SYMPES” to model speech signals is introduced. The structure of SYMPES is based on the creation of the so-called predefined “signature S={SR(n} and envelope E={EK(n}” sets. These sets are speaker and language independent. Once the speech signals are divided into frames with selected lengths, then each frame sequence Xi(n is reconstructed by means of the mathematical form Xi(n=CiEK(nSR(n. In this representation, Ci is called the gain factor, SR(n and EK(n are properly assigned from the predefined signature and envelope sets, respectively. Examples are given to exhibit the implementation of SYMPES. It is shown that for the same compression ratio or better, SYMPES yields considerably better speech quality over the commercially available coders such as G.726 (ADPCM at 16 kbps and voice excited LPC-10E (FS1015 at 2.4 kbps.

  11. Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims.

    Science.gov (United States)

    Pandey, Ghanshyam N; Ren, Xinguo; Rizavi, Hooriyah S; Conley, Robert R; Roberts, Rosalinda C; Dwivedi, Yogesh

    2008-12-01

    Teenage suicide is a major public health concern, but its neurobiology is not very well understood. Stress and major mental disorders are major risk factors for suicidal behaviour, and it has been shown that brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) are not only regulated by stress but are also altered in these illnesses. We therefore examined if BDNF/TrkB signalling is altered in the post-mortem brain of teenage suicide victims. Protein and mRNA expression of BDNF and of TrkB receptors were determined in the prefrontal cortex (PFC), Brodmann's Area 9 (BA 9), and hippocampus obtained from 29 teenage suicide victims and 25 matched normal control subjects. Protein expression was determined using the Western blot technique; mRNA levels by a quantitative RT-PCR technique. The protein expression of BDNF was significantly decreased in the PFC of teenage suicide victims compared with normal control subjects, whereas no change was observed in the hippocampus. Protein expression of TrkB full-length receptors was significantly decreased in both PFC and hippocampus of teenage suicide victims without any significant changes in the truncated form of TrkB receptors. mRNA expression of both BDNF and TrkB was significantly decreased in the PFC and hippocampus of teenage suicide victims compared with normal control subjects. These studies indicate a down-regulation of both BDNF and its receptor TrkB in the PFC and hippocampus of teenage suicide victims, which suggests that stress and altered BDNF may represent a major vulnerability factor in teenage suicidal behaviour.

  12. Absence of Doppler signal in transcranial color-coded ultrasonography may be confirmatory for brain death: A case report

    Directory of Open Access Journals (Sweden)

    Mehmet Akif Topçuoğlu

    2015-08-01

    Full Text Available Transcranial Doppler ultrasonography (TCD is a valuable tool for demonstrating cerebral circulatory arrest (CCA in the setting of brain death. Complete reversal of diastolic flow (to-and-fro flow and systolic spikes in bilateral terminal internal carotid arteries and vertebrobasilar circulation are considered as specific sonogram configurations supporting the diagnosis of CCA. Because of the possibility of sonic bone window impermeability, absence of any waveform in TCD is not confirmatory for CCA unless there is documentation of disappearance of a previously well detected signal by the same recording settings. Transcranial color-coded sonography (TCCS with B-mode imaging can reliably detect adequacy of bone windows with clarity contralateral skull and ipsilateral planum temporale visualization. Therefore, absence of detectable intracranial Doppler signal along with available ultrasound window in TCCS can confirm clinical diagnosis of brain death. We herein discuss this entity from the frame of a representative case.

  13. Phase synchronization for classification of spontaneous EEG signals in brain-computer interfaces

    OpenAIRE

    Gysels, Elly; Kunt, Murat; Celka, Patrick

    2007-01-01

    By directly analyzing brain activity, Brain-Computer Interfaces (BCIs) allow for communication that does not rely on any muscular control and therefore constitute a possible communication channel for the completely paralyzed. Typically, the user performs different mental tasks, that correspond to different output commands as recognized by the system. From the recorded brain signals (Electroencephalogram, EEG), features that characterize the mental tasks and allow their discrimination by a cla...

  14. Phase synchronization for classification of spontaneous EEG signals in brain-computer interfaces

    OpenAIRE

    Gysels, Elly

    2005-01-01

    By directly analyzing brain activity, Brain-Computer Interfaces (BCIs) allow for communication that does not rely on any muscular control and therefore constitute a possible communication channel for the completely paralyzed. Typically, the user performs different mental tasks, that correspond to different output commands as recognized by the system. From the recorded brain signals (Electroencephalogram, EEG), features that characterize the mental tasks and allow their discrimination by a cla...

  15. ASPM regulates Wnt signaling pathway activity in the developing brain

    National Research Council Canada - National Science Library

    Buchman, Joshua J; Durak, Omer; Tsai, Li-Huei

    2011-01-01

    .... Mutations in Abnormal Spindle Microcephaly (ASPM) are the most common cause of MCPH. Here, we investigate the underlying functions of Aspm in brain development and find that Aspm expression is critical for proper neurogenesis and neuronal migration...

  16. Long-Distance Interferon Signaling within the Brain Blocks Virus Spread

    Science.gov (United States)

    Ding, Siyuan

    2014-01-01

    ABSTRACT Serious permanent neurological or psychiatric dysfunction may result from virus infections in the central nervous system (CNS). Olfactory sensory neurons are in direct contact with the external environment, making them susceptible to infection by viruses that can enter the brain via the olfactory nerve. The rarity of full brain viral infections raises the important question of whether unique immune defense mechanisms protect the brain. Here we show that both RNA (vesicular stomatitis virus [VSV]) and DNA (cytomegalovirus [CMV]) virus inoculations of the nasal mucosa leading to olfactory bulb (OB) infection activate long-distance signaling that upregulates antiviral interferon (IFN)-stimulated gene (ISG) expression in uninfected remote regions of the brain. This signaling mechanism is dependent on IFN-α/β receptors deep within the brain, leading to the activation of a distant antiviral state that prevents infection of the caudal brain. In normal mice, VSV replication is limited to the OB, and these animals typically survive the infection. In contrast, mice lacking the IFN-α/β receptor succumbed to the infection, with VSV spreading throughout the brain. Chemical destruction of the olfactory sensory neurons blocked both virus trafficking into the OB and the IFN response in the caudal brain, indicating a direct signaling within the brain after intranasal infection. Most signaling within the brain occurs across the 20-nm synaptic cleft. The unique long-distance IFN signaling described here occurs across many millimeters within the brain and is critical for survival and normal brain function. IMPORTANCE The olfactory mucosa can serve as a conduit for a number of viruses to enter the brain. Yet infections in the CNS rarely occur. The mechanism responsible for protecting the brain from viruses that successfully invade the OB, the first site of infection subsequent to infection of the nasal mucosa, remains elusive. Here we demonstrate that the protection is

  17. Cooperation in mind: Motor imagery of joint and single actions is represented in different brain areas.

    Science.gov (United States)

    Wriessnegger, S C; Steyrl, D; Koschutnig, K; Müller-Putz, G R

    2016-11-01

    In this study brain activity during motor imagery (MI) of joint actions, compared to single actions and rest conditions, was investigated using functional magnetic resonance imaging (fMRI). To the best of our knowledge, this is the first neuroimaging study which directly investigated the neural correlates of joint action motor imagery. Twenty-one healthy participants imagined three different motor tasks (dancing, carrying a box, wiping). Each imagery task was performed at two kinds: alone (single action MI) or with a partner (joint action MI). We hypothesized that to imagine a cooperative task would lead to a stronger cortical activation in motor related areas due to a higher vividness and intensification of the imagery. This would be elicited by the integration of the action simulation of the virtual partner to one's own action. Comparing the joint action and the single action condition with the rest condition, we found significant activation in the precentral gyrus and precuneus respectively. Furthermore the joint action MI showed higher activation patterns in the premotor cortex (inferior and middle frontal gyrus) compared to the single action MI. The imagery of a more vivid and engaging task, like our joint action imagery, could improve rehabilitation processes since a more distributed brain activity is found. Furthermore, the joint action imagery compared to single action imagery might be an appropriate BCI task due to its clear spatial distinction of activation. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. EGFR Signaling in the Brain Is Necessary for Olfactory Learning in "Drosophila" Larvae

    Science.gov (United States)

    Rahn, Tasja; Leippe, Matthias; Roeder, Thomas; Fedders, Henning

    2013-01-01

    Signaling via the epidermal growth factor receptor (EGFR) pathway has emerged as one of the key mechanisms in the development of the central nervous system in "Drosophila melanogaster." By contrast, little is known about the functions of EGFR signaling in the differentiated larval brain. Here, promoter-reporter lines of EGFR and its most prominent…

  19. Prompt recognition of brain states by their EEG signals

    DEFF Research Database (Denmark)

    Peters, B.O.; Pfurtscheller, G.; Flyvbjerg, H.

    1997-01-01

    Brain states corresponding to intention of movement of left and right index finger and right foot are classified by a ''committee'' of artificial neural networks processing individual channels of 56-electrode electroencephalograms (EEGs). Correct recognition is achieved in 83% of cases not previo......Brain states corresponding to intention of movement of left and right index finger and right foot are classified by a ''committee'' of artificial neural networks processing individual channels of 56-electrode electroencephalograms (EEGs). Correct recognition is achieved in 83% of cases...... not previously seen by the system on the basis of 1 sec long EEGs....

  20. Mechanisms of CCK signaling from gut to brain

    OpenAIRE

    Raybould, Helen E.

    2007-01-01

    Following the observation that exogenous peripheral injection of CCK could inhibit food intake, the mechanisms by which CCK influences the gut-brain pathway has been the subject of intense study for nearly thirty years. Recently, it has become evident that the system is more complex and that the consequences of CCK’s action on the gut-brain pathway are more far reaching than previously recognized. This review will examine the recent evidence showing the role of CCK and CCK1Rs in modulating ex...

  1. Insulin-like growth factor I signaling for brain recovery and exercise ability in brain ischemic rats.

    Science.gov (United States)

    Chang, Heng-Chih; Yang, Yea-Ru; Wang, Paulus S; Kuo, Chia-Hua; Wang, Ray-Yau

    2011-12-01

    Exercise increases neuron survival and plasticity in the adult brain by enhancing the uptake of insulin-like growth factor I (IGF-I). Exercise also reduces the infarct volume in the ischemic brain and improves motor function after such a brain insult. However, the underlying mechanisms are not fully known. The purpose of this study was to investigate the involvement of IGF-I signaling in neuroprotection after exercise. Rats were assigned to one of four groups: middle cerebral artery occlusion (MCAO) without exercise training (MC), MCAO with exercise training (ME), MCAO with IGF-I receptor inhibitor and without exercise training (MAg), and MCAO with IGF-I receptor inhibitor and exercise training (MEAg). Rats in the ME and MEAg groups underwent treadmill training for 14 d, and rats in the MC and MAg groups served as controls. After the final intervention, rats were sacrificed under anesthesia, and samples were collected from the affected motor cortex, striatum, and plasma. IGF-I and p-Akt levels in the affected motor cortex and the striatum of the ME group were significantly higher than those in the MC group, with significant decreases in infarct volume and improvements in motor function. However, IGF-I receptor inhibitor eliminated these effects and decreased the exercise ability. The brain IGF-I signaling strongly correlated with exercise ability. Exercise-enhanced IGF-I entrance into ischemic brain and IGF-I signaling was related to exercise-mediated neuroprotection. IGF-1 signaling also affected the ability to exercise after brain ischemia.

  2. Human-machine interface based on muscular and brain signals applied to a robotic wheelchair

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, A; Silva, R L; Celeste, W C; Filho, T F Bastos; Filho, M Sarcinelli [Electrical Engineering Department, Federal University of Espirito Santo (UFES), Av. Fernando Ferrari, 514, Vitoria, 29075-910 (Brazil)

    2007-11-15

    This paper presents a Human-Machine Interface (HMI) based on the signals generated by eye blinks or brain activity. The system structure and the signal acquisition and processing are shown. The signals used in this work are either the signal associated to the muscular movement corresponding to an eye blink or the brain signal corresponding to visual information processing. The variance is the feature extracted from such signals in order to detect the intention of the user. The classification is performed by a variance threshold which is experimentally determined for each user during the training stage. The command options, which are going to be sent to the commanded device, are presented to the user in the screen of a PDA (Personal Digital Assistant). In the experiments here reported, a robotic wheelchair is used as the device being commanded.

  3. Review of Sparse Representation-Based Classification Methods on EEG Signal Processing for Epilepsy Detection, Brain-Computer Interface and Cognitive Impairment

    OpenAIRE

    Wen, Dong; Jia, Peilei; Lian, Qiusheng; Zhou, Yanhong; LU, CHENGBIAO

    2016-01-01

    At present, the sparse representation-based classification (SRC) has become an important approach in electroencephalograph (EEG) signal analysis, by which the data is sparsely represented on the basis of a fixed dictionary or learned dictionary and classified based on the reconstruction criteria. SRC methods have been used to analyze the EEG signals of epilepsy, cognitive impairment and brain computer interface (BCI), which made rapid progress including the improvement in computational accura...

  4. Physiological consequences of membrane-initiated estrogen signaling in the brain

    OpenAIRE

    Roepke, Troy A.; Ronnekleiv, Oline K.; Kelly, Martin J.

    2011-01-01

    Many of the actions of 17beta-estradiol (E2) in the central nervous system (CNS) are mediated via the classical nuclear steroid receptors, ERalpha and ERbeta, which interact with the estrogen response element to modulate gene expression. In addition to the nuclear-initiated estrogen signaling, E2 signaling in the brain can occur rapidly within minutes prior to any sufficient effects on transcription of relevant genes. These rapid, membrane-initiated E2 signaling mechanisms have now been chara...

  5. Sex differences in brain-derived neurotrophic factor signaling: Functions and implications.

    Science.gov (United States)

    Wei, Yi-Chao; Wang, Shao-Ran; Xu, Xiao-Hong

    2017-01-02

    Brain-derived neurotrophic factor (BDNF) regulates diverse processes such as neuronal survival, differentiation, and plasticity. Accumulating evidence suggests that molecular events that direct sexual differentiation of the brain interact with BDNF signaling pathways. This Mini-Review first examines potential hormonal and epigenetic mechanisms through which sex influences BDNF signaling. We then examine how sex-specific regulation of BDNF signaling supports the development and function of sexually dimorphic neural circuits that underlie male-specific genital reflexes in rats and song production in birds. Finally, we discuss the implications of sex differences in BDNF signaling for gender-biased presentation of neurological and psychiatric diseases such as Alzheimer's disease. Although this Mini-Review focuses on BDNF, we try to convey the general message that sex influences brain functions in complex ways and underscore the requirement for and challenge of expanding research on sex differences in neuroscience. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Brain Signal Analysis Using Different Types of Music

    OpenAIRE

    Siti Ayuni Mohd Nasir; Wan Mahani Hafizah Wan Mahmud

    2015-01-01

    Music is able to improve certain functions of human body physiologically and psychologically. Music also can improve attention, memory, and even mental math ability by listening to the music before performing any task. The purpose of this study is to study the relation between types of music and brainwaves signal that is differences in state of relaxation and attention states. The Electroencephalography (EEG) signal was recorded using PowerLab, Dual Bio Amp and computer to observes and record...

  7. Intelligent Automatic Right-Left Sign Lamp Based on Brain Signal Recognition System

    Science.gov (United States)

    Winda, A.; Sofyan; Sthevany; Vincent, R. S.

    2017-12-01

    Comfort as a part of the human factor, plays important roles in nowadays advanced automotive technology. Many of the current technologies go in the direction of automotive driver assistance features. However, many of the driver assistance features still require physical movement by human to enable the features. In this work, the proposed method is used in order to make certain feature to be functioning without any physical movement, instead human just need to think about it in their mind. In this work, brain signal is recorded and processed in order to be used as input to the recognition system. Right-Left sign lamp based on the brain signal recognition system can potentially replace the button or switch of the specific device in order to make the lamp work. The system then will decide whether the signal is ‘Right’ or ‘Left’. The decision of the Right-Left side of brain signal recognition will be sent to a processing board in order to activate the automotive relay, which will be used to activate the sign lamp. Furthermore, the intelligent system approach is used to develop authorized model based on the brain signal. Particularly Support Vector Machines (SVMs)-based classification system is used in the proposed system to recognize the Left-Right of the brain signal. Experimental results confirm the effectiveness of the proposed intelligent Automatic brain signal-based Right-Left sign lamp access control system. The signal is processed by Linear Prediction Coefficient (LPC) and Support Vector Machines (SVMs), and the resulting experiment shows the training and testing accuracy of 100% and 80%, respectively.

  8. Abnormalities of Dopamine D3 Receptor Signaling in the Diseased Brain

    Science.gov (United States)

    Prieto, G Aleph

    2017-01-01

    Dopamine D3 receptors (D3R) modulate neuronal activity in several brain regions including cortex, striatum, cerebellum, and hippocampus. A growing body of evidence suggests that aberrant D3R signaling contributes to multiple brain diseases, such as Parkinson’s disease, essential tremor, schizophrenia, and addiction. In line with these findings, D3R has emerged as a potential target in the treatment of neurological disorders. However, the mechanisms underlying neuronal D3R signaling are poorly understood, either in healthy or diseased brain. Here, I review the molecular mechanisms involved in D3R signaling via monomeric D3R and heteromeric receptor complexes (e.g., D3R-D1R, D3R-D2R, D3R-A2aR, and D3R-D3nf). I focus on D3R signaling pathways that, according to recent reports, contribute to pathological brain states. In particular, I describe evidence on both quantitative (e.g., increased number or affinity) and qualitative (e.g., switched signaling) changes in D3R that has been associated with brain dysfunction. I conclude with a description of basic mechanisms that modulate D3R signaling such as desensitization, as disruption of these mechanisms may underlie pathological changes in D3R signaling. Because several lines of evidence support the idea that imbalances in D3R signaling alter neural function, a better understanding of downstream D3R pathways is likely to reveal novel therapeutic strategies toward dopamine-related brain disorders. PMID:28855798

  9. Effects of Bisphenol A on glucose homeostasis and brain insulin signaling pathways in male mice.

    Science.gov (United States)

    Fang, Fangfang; Chen, Donglong; Yu, Pan; Qian, Wenyi; Zhou, Jing; Liu, Jingli; Gao, Rong; Wang, Jun; Xiao, Hang

    2015-02-01

    The potential effects of Bisphenol A (BPA) on peripheral insulin resistance have recently gained more attention, however, its functions on brain insulin resistance are still unknown. The aim of the present study was to investigate the effects of BPA on insulin signaling and glucose transport in mouse brain. The male mice were administrated of 100 μg/kg/day BPA or vehicle for 15 days then challenged with glucose and insulin tolerance tests. The insulin levels were detected with radioimmunoassay (RIA), and the insulin signaling pathways were investigated by Western blot. Our results revealed that BPA significantly increased peripheral plasma insulin levels, and decreased the insulin signals including phosphorylated insulin receptor (p-IR), phosphorylated insulin receptor substrate 1 (p-IRS1), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and phosphorylated extracellular regulated protein kinases (p-ERK1/2) in the brain, though insulin expression in both hippocampus and profrontal cortex was increased. In parallel, BPA exposure might contribute to glucose transport disturbance in the brain since the expression of glucose transporters were markedly decreased. In conclusion, BPA exposure perturbs the insulin signaling and glucose transport in the brain, therefore, it might be a risk factor for brain insulin resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. A signaling network for patterning of neuronal connectivity in the Drosophila brain.

    Directory of Open Access Journals (Sweden)

    Mohammed Srahna

    2006-10-01

    Full Text Available The precise number and pattern of axonal connections generated during brain development regulates animal behavior. Therefore, understanding how developmental signals interact to regulate axonal extension and retraction to achieve precise neuronal connectivity is a fundamental goal of neurobiology. We investigated this question in the developing adult brain of Drosophila and find that it is regulated by crosstalk between Wnt, fibroblast growth factor (FGF receptor, and Jun N-terminal kinase (JNK signaling, but independent of neuronal activity. The Rac1 GTPase integrates a Wnt-Frizzled-Disheveled axon-stabilizing signal and a Branchless (FGF-Breathless (FGF receptor axon-retracting signal to modulate JNK activity. JNK activity is necessary and sufficient for axon extension, whereas the antagonistic Wnt and FGF signals act to balance the extension and retraction required for the generation of the precise wiring pattern.

  11. Permanency analysis on human electroencephalogram signals for pervasive Brain-Computer Interface systems.

    Science.gov (United States)

    Sadeghi, Koosha; Junghyo Lee; Banerjee, Ayan; Sohankar, Javad; Gupta, Sandeep K S

    2017-07-01

    Brain-Computer Interface (BCI) systems use some permanent features of brain signals to recognize their corresponding cognitive states with high accuracy. However, these features are not perfectly permanent, and BCI system should be continuously trained over time, which is tedious and time consuming. Thus, analyzing the permanency of signal features is essential in determining how often to repeat training. In this paper, we monitor electroencephalogram (EEG) signals, and analyze their behavior through continuous and relatively long period of time. In our experiment, we record EEG signals corresponding to rest state (eyes open and closed) from one subject everyday, for three and a half months. The results show that signal features such as auto-regression coefficients remain permanent through time, while others such as power spectral density specifically in 5-7 Hz frequency band are not permanent. In addition, eyes open EEG data shows more permanency than eyes closed data.

  12. Does human body odor represent a significant and rewarding social signal to individuals high in social openness?

    Science.gov (United States)

    Lübke, Katrin T; Croy, Ilona; Hoenen, Matthias; Gerber, Johannes; Pause, Bettina M; Hummel, Thomas

    2014-01-01

    Across a wide variety of domains, experts differ from novices in their response to stimuli linked to their respective field of expertise. It is currently unknown whether similar patterns can be observed with regard to social expertise. The current study therefore focuses on social openness, a central social skill necessary to initiate social contact. Human body odors were used as social cues, as they inherently signal the presence of another human being. Using functional MRI, hemodynamic brain responses to body odors of women reporting a high (n = 14) or a low (n = 12) level of social openness were compared. Greater activation within the inferior frontal gyrus and the caudate nucleus was observed in high socially open individuals compared to individuals low in social openness. With the inferior frontal gyrus being a crucial part of the human mirror neuron system, and the caudate nucleus being implicated in social reward, it is discussed whether human body odor might constitute more of a significant and rewarding social signal to individuals high in social openness compared to individuals low in social openness process.

  13. Does human body odor represent a significant and rewarding social signal to individuals high in social openness?

    Directory of Open Access Journals (Sweden)

    Katrin T Lübke

    Full Text Available Across a wide variety of domains, experts differ from novices in their response to stimuli linked to their respective field of expertise. It is currently unknown whether similar patterns can be observed with regard to social expertise. The current study therefore focuses on social openness, a central social skill necessary to initiate social contact. Human body odors were used as social cues, as they inherently signal the presence of another human being. Using functional MRI, hemodynamic brain responses to body odors of women reporting a high (n = 14 or a low (n = 12 level of social openness were compared. Greater activation within the inferior frontal gyrus and the caudate nucleus was observed in high socially open individuals compared to individuals low in social openness. With the inferior frontal gyrus being a crucial part of the human mirror neuron system, and the caudate nucleus being implicated in social reward, it is discussed whether human body odor might constitute more of a significant and rewarding social signal to individuals high in social openness compared to individuals low in social openness process.

  14. Electrophysiological Signals of Familiarity and Recency in the Infant Brain

    Science.gov (United States)

    Snyder, Kelly A.; Garza, John; Zolot, Liza; Kresse, Anna

    2010-01-01

    Electrophysiological work in nonhuman primates has established the existence of multiple types of signals in the temporal lobe that contribute to recognition memory, including information regarding a stimulus's relative novelty, familiarity, and recency of occurrence. We used high-density event-related potentials (ERPs) to examine whether young…

  15. Signaling by SHH rescues facial defects following blockade in the brain.

    Science.gov (United States)

    Chong, H Jonathan; Young, Nathan M; Hu, Diane; Jeong, Juhee; McMahon, Andrew P; Hallgrimsson, Benedikt; Marcucio, Ralph S

    2012-02-01

    The Frontonasal Ectodermal Zone (FEZ) is a signaling center in the face that expresses Sonic hedgehog (Shh) and regulates patterned growth of the upper jaw. Blocking SHH in the forebrain blocks Shh expression in the FEZ and creates malformations resembling holoprosencephaly (HPE), while inhibition of BMP signaling in the mesenchyme blocks FEZ formation and causes similar dysmorphology. Thus, the brain could regulate FEZ formation by SHH or BMP signaling, and if so, activating one of these pathways in the face might alleviate the effects of repression of SHH in the brain. We blocked SHH signaling in the brain while adding SHH or BMP between the neural and facial ectoderm of the frontonasal process. When applied early, SHH restored Shh expression in the FEZ and significantly improved shape outcomes, which contrasts with our previous experiments that showed later SHH treatments have no effect. BMP-soaked beads introduced early and late caused apoptosis that exacerbated malformations. Finally, removal of Smoothened from neural crest cells did not inhibit Shh expression in the FEZ. Collectively, this work suggests that a direct, time-sensitive SHH signal from the brain is required for the later induction of Shh in the FEZ. We propose a testable model of FEZ activation and discuss signaling mediators that may regulate these interactions.

  16. ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size.

    Science.gov (United States)

    Kadir, Rotem; Harel, Tamar; Markus, Barak; Perez, Yonatan; Bakhrat, Anna; Cohen, Idan; Volodarsky, Michael; Feintsein-Linial, Miora; Chervinski, Elana; Zlotogora, Joel; Sivan, Sara; Birnbaum, Ramon Y; Abdu, Uri; Shalev, Stavit; Birk, Ohad S

    2016-03-01

    Primary microcephaly is a congenital neurodevelopmental disorder of reduced head circumference and brain volume, with fewer neurons in the cortex of the developing brain due to premature transition between symmetrical and asymmetrical cellular division of the neuronal stem cell layer during neurogenesis. We now show through linkage analysis and whole exome sequencing, that a dominant mutation in ALFY, encoding an autophagy scaffold protein, causes human primary microcephaly. We demonstrate the dominant effect of the mutation in drosophila: transgenic flies harboring the human mutant allele display small brain volume, recapitulating the disease phenotype. Moreover, eye-specific expression of human mutant ALFY causes rough eye phenotype. In molecular terms, we demonstrate that normally ALFY attenuates the canonical Wnt signaling pathway via autophagy-dependent removal specifically of aggregates of DVL3 and not of Dvl1 or Dvl2. Thus, autophagic attenuation of Wnt signaling through removal of Dvl3 aggregates by ALFY acts in determining human brain size.

  17. ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size.

    Directory of Open Access Journals (Sweden)

    Rotem Kadir

    2016-03-01

    Full Text Available Primary microcephaly is a congenital neurodevelopmental disorder of reduced head circumference and brain volume, with fewer neurons in the cortex of the developing brain due to premature transition between symmetrical and asymmetrical cellular division of the neuronal stem cell layer during neurogenesis. We now show through linkage analysis and whole exome sequencing, that a dominant mutation in ALFY, encoding an autophagy scaffold protein, causes human primary microcephaly. We demonstrate the dominant effect of the mutation in drosophila: transgenic flies harboring the human mutant allele display small brain volume, recapitulating the disease phenotype. Moreover, eye-specific expression of human mutant ALFY causes rough eye phenotype. In molecular terms, we demonstrate that normally ALFY attenuates the canonical Wnt signaling pathway via autophagy-dependent removal specifically of aggregates of DVL3 and not of Dvl1 or Dvl2. Thus, autophagic attenuation of Wnt signaling through removal of Dvl3 aggregates by ALFY acts in determining human brain size.

  18. Getting signals into the brain: visual prosthetics through thalamic microstimulation

    Science.gov (United States)

    Pezaris, John S.; Eskandar, Emad N.

    2010-01-01

    Common causes of blindness are diseases that affect the ocular structures, such as glaucoma, retinitis pigmentosa, and macular degeneration, rendering the eyes no longer sensitive to light. The visual pathway, however, as a predominantly central structure, is largely spared in these cases. It is thus widely thought that a device-based prosthetic approach to restoration of visual function will be effective and will enjoy similar success as cochlear implants have for restoration of auditory function. In this article the authors review the potential locations for stimulation electrode placement for visual prostheses, assessing the anatomical and functional advantages and disadvantages of each. Of particular interest to the neurosurgical community is placement of deep brain stimulating electrodes in thalamic structures that has shown substantial promise in an animal model. The theory of operation of visual prostheses is discussed, along with a review of the current state of knowledge. Finally, the visual prosthesis is proposed as a model for a general high-fidelity machine-brain interface. PMID:19569894

  19. PACAP38/PAC1 signaling induces bone marrow-derived cells homing to ischemic brain.

    Science.gov (United States)

    Lin, Chen-Huan; Chiu, Lian; Lee, Hsu-Tung; Chiang, Chun-Wei; Liu, Shih-Ping; Hsu, Yung-Hsiang; Lin, Shinn-Zong; Hsu, Chung Y; Hsieh, Chia-Hung; Shyu, Woei-Cherng

    2015-04-01

    Understanding stem cell homing, which is governed by environmental signals from the surrounding niche, is important for developing effective stem cell-based repair strategies. The molecular mechanism by which the brain under ischemic stress recruits bone marrow-derived cells (BMDCs) to the vascular niche remains poorly characterized. Here we report that hypoxia-inducible factor-1α (HIF-1α) activation upregulates pituitary adenylate cyclase-activating peptide 38 (PACAP38), which in turn activates PACAP type 1 receptor (PAC1) under hypoxia in vitro and cerebral ischemia in vivo. BMDCs homing to endothelial cells in the ischemic brain are mediated by HIF-1α activation of the PACAP38-PAC1 signaling cascade followed by upregulation of cellular prion protein and α6-integrin to enhance the ability of BMDCs to bind laminin in the vascular niche. Exogenous PACAP38 confers a similar effect in facilitating BMDCs homing into the ischemic brain, resulting in reduction of ischemic brain injury. These findings suggest a novel HIF-1α-activated PACAP38-PAC1 signaling process in initiating BMDCs homing into the ischemic brain for reducing brain injury and enhancing functional recovery after ischemic stroke. © 2015 The Authors. STEM CELLS Published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  20. Radial glial neural progenitors regulate nascent brain vascular network stabilization via inhibition of Wnt signaling.

    Directory of Open Access Journals (Sweden)

    Shang Ma

    Full Text Available The cerebral cortex performs complex cognitive functions at the expense of tremendous energy consumption. Blood vessels in the brain are known to form stereotypic patterns that facilitate efficient oxygen and nutrient delivery. Yet little is known about how vessel development in the brain is normally regulated. Radial glial neural progenitors are well known for their central role in orchestrating brain neurogenesis. Here we show that, in the late embryonic cortex, radial glial neural progenitors also play a key role in brain angiogenesis, by interacting with nascent blood vessels and regulating vessel stabilization via modulation of canonical Wnt signaling. We find that ablation of radial glia results in vessel regression, concomitant with ectopic activation of Wnt signaling in endothelial cells. Direct activation of Wnt signaling also results in similar vessel regression, while attenuation of Wnt signaling substantially suppresses regression. Radial glial ablation and ectopic Wnt pathway activation leads to elevated endothelial expression of matrix metalloproteinases, while inhibition of metalloproteinase activity significantly suppresses vessel regression. These results thus reveal a previously unrecognized role of radial glial progenitors in stabilizing nascent brain vascular network and provide novel insights into the molecular cascades through which target neural tissues regulate vessel stabilization and patterning during development and throughout life.

  1. An Artificial Neural Network Based Robot Controller that Uses Rat’s Brain Signals

    Directory of Open Access Journals (Sweden)

    Marsel Mano

    2013-04-01

    Full Text Available Brain machine interface (BMI has been proposed as a novel technique to control prosthetic devices aimed at restoring motor functions in paralyzed patients. In this paper, we propose a neural network based controller that maps rat’s brain signals and transforms them into robot movement. First, the rat is trained to move the robot by pressing the right and left lever in order to get food. Next, we collect brain signals with four implanted electrodes, two in the motor cortex and two in the somatosensory cortex area. The collected data are used to train and evaluate different artificial neural controllers. Trained neural controllers are employed online to map brain signals and transform them into robot motion. Offline and online classification results of rat’s brain signals show that the Radial Basis Function Neural Networks (RBFNN outperforms other neural networks. In addition, online robot control results show that even with a limited number of electrodes, the robot motion generated by RBFNN matched the motion generated by the left and right lever position.

  2. Insulin signaling disruption in male mice due to perinatal bisphenol A exposure: Role of insulin signaling in the brain.

    Science.gov (United States)

    Fang, Fangfang; Gao, Yue; Wang, Tingwei; Chen, Donglong; Liu, Jingli; Qian, Wenyi; Cheng, Jie; Gao, Rong; Wang, Jun; Xiao, Hang

    2016-03-14

    Bisphenol A (BPA), an environmental estrogenic endocrine disruptor, is widely used for producing polycarbonate plastics and epoxy resins. Available data have shown that perinatal exposure to BPA contributes to peripheral insulin resistance, while in the present study, we aimed to investigate the effects of perinatal BPA exposure on insulin signaling and glucose transport in the cortex of offspring mice. The pregnant mice were administrated either vehicle or BPA (100 μg/kg/day) at three perinatal stages. Stage I: from day 6 of gestation until parturition (P6-PND0 fetus exposure); Stage II: from lactation until delactation (PND0-PND21 newborn exposure) and Stage III: from day 6 of pregnancy until delactation (P6-PND21 fetus and newborn exposure). At 8 months of age for the offspring mice, the insulin signaling pathways and glucose transporters (GLUTs) were detected. Our data indicated that the insulin signaling including insulin, phosphorylated insulin receptor (IR), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and phosphorylated extracellular signal regulated protein kinase (p-ERK) were significantly decreased in the brain. In parallel, GLUTs (GLUT1/3/4) were obviously decreased as well in BPA-treated group in mice brain. Noteworthily, the phosphorylated tau (p-tau) and amyloid precursor protein (APP) were markedly up-regulated in all BPA-treated groups. These results, taken together, suggest the adverse effects of BPA on insulin signaling and GLUTs, which might subsequently contribute to the increment of p-tau and APP in the brain of adult offspring. Therefore, perinatal BPA exposure might be a risk factor for the long-term neurodegenerative changes in offspring male mice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Automatic integration of confidence in the brain valuation signal.

    Science.gov (United States)

    Lebreton, Maël; Abitbol, Raphaëlle; Daunizeau, Jean; Pessiglione, Mathias

    2015-08-01

    A key process in decision-making is estimating the value of possible outcomes. Growing evidence suggests that different types of values are automatically encoded in the ventromedial prefrontal cortex (VMPFC). Here we extend this idea by suggesting that any overt judgment is accompanied by a second-order valuation (a confidence estimate), which is also automatically incorporated in VMPFC activity. In accordance with the predictions of our normative model of rating tasks, two behavioral experiments showed that confidence levels were quadratically related to first-order judgments (age, value or probability ratings). The analysis of three functional magnetic resonance imaging data sets using similar rating tasks confirmed that the quadratic extension of first-order ratings (our proxy for confidence) was encoded in VMPFC activity, even if no confidence judgment was required of the participants. Such an automatic aggregation of value and confidence in a same brain region might provide insight into many distortions of judgment and choice.

  4. DAMP signaling is a key pathway inducing immune modulation after brain injury.

    Science.gov (United States)

    Liesz, Arthur; Dalpke, Alexander; Mracsko, Eva; Antoine, Daniel J; Roth, Stefan; Zhou, Wei; Yang, Huan; Na, Shin-Young; Akhisaroglu, Mustafa; Fleming, Thomas; Eigenbrod, Tatjana; Nawroth, Peter P; Tracey, Kevin J; Veltkamp, Roland

    2015-01-14

    Acute brain lesions induce profound alterations of the peripheral immune response comprising the opposing phenomena of early immune activation and subsequent immunosuppression. The mechanisms underlying this brain-immune signaling are largely unknown. We used animal models for experimental brain ischemia as a paradigm of acute brain lesions and additionally investigated a large cohort of stroke patients. We analyzed release of HMGB1 isoforms by mass spectrometry and investigated its inflammatory potency and signaling pathways by immunological in vivo and in vitro techniques. Features of the complex behavioral sickness behavior syndrome were characterized by homecage behavior analysis. HMGB1 downstream signaling, particularly with RAGE, was studied in various transgenic animal models and by pharmacological blockade. Our results indicate that the cytokine-inducing, fully reduced isoform of HMGB1 was released from the ischemic brain in the hyperacute phase of stroke in mice and patients. Cytokines secreted in the periphery in response to brain injury induced sickness behavior, which could be abrogated by inhibition of the HMGB1-RAGE pathway or direct cytokine neutralization. Subsequently, HMGB1-release induced bone marrow egress and splenic proliferation of bone marrow-derived suppressor cells, inhibiting the adaptive immune responses in vivo and vitro. Furthermore, HMGB1-RAGE signaling resulted in functional exhaustion of mature monocytes and lymphopenia, the hallmarks of immune suppression after extensive ischemia. This study introduces the HMGB1-RAGE-mediated pathway as a key mechanism explaining the complex postischemic brain-immune interactions. Copyright © 2015 the authors 0270-6474/15/350583-16$15.00/0.

  5. Tracking of electroencephalography signals across brain lobes using motion estimation and cross-correlation

    Science.gov (United States)

    Lim, Seng Hooi; Nisar, Humaira; Yap, Vooi Voon; Shim, Seong-O.

    2015-11-01

    Electroencephalography (EEG) is the signal generated by electrical activity in the human brain. EEG topographic maps (topo-maps) give an idea of brain activation. Functional connectivity helps to find functionally integrated relationship between spatially separated brain regions. Brain connectivity can be measured by several methods. The classical methods calculate the coherence and correlation of the signal. We have developed an algorithm to map functional neural connectivity in the brain by using a full search block matching motion estimation algorithm. We have used oddball paradigm to examine the flow of activation across brain lobes for a specific activity. In the first step, the EEG signal is converted into topo-maps. The flow of activation between consecutive frames is tracked using full search block motion estimation, which appears in the form of motion vectors. In the second step, vector median filtering is used to obtain a smooth motion field by removing the unwanted noise. For each topo-map, several activation paths are tracked across various brain lobes. We have also developed correlation activity maps by following the correlation coefficient paths between electrodes. These paths are selected when the correlation coefficient between electrodes is >70%. We have compared the motion estimation path with the correlation coefficient activation maps. The tracked paths obtained by using motion estimation and correlation give very similar results. The inter-subject comparison shows that four out of five subjects tracked path involves all four (occipital, temporal, parietal, frontal) brain lobes for the same stimuli. The intra-subject analysis shows that three out of five subjects show different tracked lobes for different stimuli.

  6. Identification and analysis of signaling networks potentially involved in breast carcinoma metastasis to the brain.

    Directory of Open Access Journals (Sweden)

    Feng Li

    Full Text Available Brain is a common site of breast cancer metastasis associated with significant neurologic morbidity, decreased quality of life, and greatly shortened survival. However, the molecular and cellular mechanisms underpinning brain colonization by breast carcinoma cells are poorly understood. Here, we used 2D-DIGE (Difference in Gel Electrophoresis proteomic analysis followed by LC-tandem mass spectrometry to identify the proteins differentially expressed in brain-targeting breast carcinoma cells (MB231-Br compared with parental MDA-MB-231 cell line. Between the two cell lines, we identified 12 proteins consistently exhibiting greater than 2-fold (p<0.05 difference in expression, which were associated by the Ingenuity Pathway Analysis (IPA with two major signaling networks involving TNFα/TGFβ-, NFκB-, HSP-70-, TP53-, and IFNγ-associated pathways. Remarkably, highly related networks were revealed by the IPA analysis of a list of 19 brain-metastasis-associated proteins identified recently by the group of Dr. A. Sierra using MDA-MB-435-based experimental system (Martin et al., J Proteome Res 2008 7:908-20, or a 17-gene classifier associated with breast cancer brain relapse reported by the group of Dr. J. Massague based on a microarray analysis of clinically annotated breast tumors from 368 patients (Bos et al., Nature 2009 459: 1005-9. These findings, showing that different experimental systems and approaches (2D-DIGE proteomics used on brain targeting cell lines or gene expression analysis of patient samples with documented brain relapse yield highly related signaling networks, suggest strongly that these signaling networks could be essential for a successful colonization of the brain by metastatic breast carcinoma cells.

  7. Recovering fNIRS brain signals: physiological interference suppression with independent component analysis

    Science.gov (United States)

    Zhang, Y.; Shi, M.; Sun, J.; Yang, C.; Zhang, Yajuan; Scopesi, F.; Makobore, P.; Chin, C.; Serra, G.; Wickramasinghe, Y. A. B. D.; Rolfe, P.

    2015-02-01

    Brain activity can be monitored non-invasively by functional near-infrared spectroscopy (fNIRS), which has several advantages in comparison with other methods, such as flexibility, portability, low cost and fewer physical restrictions. However, in practice fNIRS measurements are often contaminated by physiological interference arising from cardiac contraction, breathing and blood pressure fluctuations, thereby severely limiting the utility of the method. Hence, further improvement is necessary to reduce or eliminate such interference in order that the evoked brain activity information can be extracted reliably from fNIRS data. In the present paper, the multi-distance fNIRS probe configuration has been adopted. The short-distance fNIRS measurement is treated as the virtual channel and the long-distance fNIRS measurement is treated as the measurement channel. Independent component analysis (ICA) is employed for the fNIRS recordings to separate the brain signals and the interference. Least-absolute deviation (LAD) estimator is employed to recover the brain activity signals. We also utilized Monte Carlo simulations based on a five-layer model of the adult human head to evaluate our methodology. The results demonstrate that the ICA algorithm has the potential to separate physiological interference in fNIRS data and the LAD estimator could be a useful criterion to recover the brain activity signals.

  8. Beacon signal in transcranial color coded ultrasound: A sign for brain death

    Directory of Open Access Journals (Sweden)

    Mehmet Akif Topçuoğlu

    2014-04-01

    Full Text Available A widely under-recognized brain-death confirming transcranial ultrasonography pattern resembling the red-blue beacon signal was demonstrated. Familiarity to this distinct and characteristic ultrasonic pattern seems to be important in the perspective of point-of-care neurological ultrasound use and knobology.

  9. Tryptophan as an evolutionarily conserved signal to brain serotonin : Molecular evidence and psychiatric implications

    NARCIS (Netherlands)

    Russo, Sascha; Kema, Ido P.; Bosker, Fokko; Haavik, Jan; Korf, Jakob

    2009-01-01

    The role of serotonin (5-HT) in psychopathology has been investigated for decades. Among others, symptoms of depression, panic, aggression and suicidality have been associated with serotonergic dysfunction. Here we summarize the evidence that low brain 5-HT signals a metabolic imbalance that is

  10. Intelligent Technique for Signal Processing to Identify the Brain Disorder for Epilepsy Captures Using Fuzzy Systems

    Directory of Open Access Journals (Sweden)

    Gurumurthy Sasikumar

    2016-01-01

    Full Text Available The new direction of understand the signal that is created from the brain organization is one of the main chores in the brain signal processing. Amid all the neurological disorders the human brain epilepsy is measured as one of the extreme prevalent and then programmed artificial intelligence detection technique is an essential due to the crooked and unpredictable nature of happening of epileptic seizures. We proposed an Improved Fuzzy firefly algorithm, which would enhance the classification of the brain signal efficiently with minimum iteration. An important bunching technique created on fuzzy logic is the Fuzzy C means. Together in the feature domain with the spatial domain the features gained after multichannel EEG signals remained combined by means of fuzzy algorithms. And for better precision segmentation process the firefly algorithm is applied to optimize the Fuzzy C-means membership function. Simultaneously for the efficient clustering method the convergence criteria are set. On the whole the proposed technique yields more accurate results and that gives an edge over other techniques. This proposed algorithm result compared with other algorithms like fuzzy c means algorithm and PSO algorithm.

  11. Thermosensory signaling by TRPM is processed by brain serotonergic neurons to produce planarian thermotaxis.

    Science.gov (United States)

    Inoue, Takeshi; Yamashita, Taiga; Agata, Kiyokazu

    2014-11-19

    For most organisms, sensitive recognition of even slight changes in environmental temperature is essential for adjusting their behavioral strategies to ensure homeostasis and survival. However, much remains to be understood about the molecular and cellular processes that regulate thermosensation and the corresponding behavioral responses. Planarians display clear thermotaxis, although they have a relatively simple brain. Here, we devised a quantitative thermotaxis assay and unraveled a neural pathway involved in planarian thermotaxis by combinatory behavioral assays and RNAi analysis. We found that thermosensory neurons that expressed a planarian Dugesia japonica homolog of the Transient Receptor Potential Melastatin family a (DjTRPMa) gene were required for the thermotaxis. Interestingly, although these thermosensory neurons are distributed throughout their body, planarians with a dysfunctional brain due to regeneration-dependent conditional gene knockdown (Readyknock) of the synaptotagmin gene completely lost their thermotactic behavior. These results suggest that brain function is required as a central processor for the thermosensory response. Therefore, we investigated the type(s) of brain neurons involved in processing the thermal signals by gene knockdown of limiting enzymes for neurotransmitter biosynthesis in the brain. We found that serotonergic neurons with dendrites that were elongated toward DjTRPMa-expressing thermosensory neurons might be required for the processing of signals from thermosensory neurons that results in thermotaxis. These results suggest that serotonergic neurons in the brain may interact with thermosensory neurons activated by TRPM ion channels to produce thermotaxis in planarians. Copyright © 2014 the authors 0270-6474/14/3415701-14$15.00/0.

  12. Automated classification of brain tumor type in whole-slide digital pathology images using local representative tiles.

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    Barker, Jocelyn; Hoogi, Assaf; Depeursinge, Adrien; Rubin, Daniel L

    2016-05-01

    Computerized analysis of digital pathology images offers the potential of improving clinical care (e.g. automated diagnosis) and catalyzing research (e.g. discovering disease subtypes). There are two key challenges thwarting computerized analysis of digital pathology images: first, whole slide pathology images are massive, making computerized analysis inefficient, and second, diverse tissue regions in whole slide images that are not directly relevant to the disease may mislead computerized diagnosis algorithms. We propose a method to overcome both of these challenges that utilizes a coarse-to-fine analysis of the localized characteristics in pathology images. An initial surveying stage analyzes the diversity of coarse regions in the whole slide image. This includes extraction of spatially localized features of shape, color and texture from tiled regions covering the slide. Dimensionality reduction of the features assesses the image diversity in the tiled regions and clustering creates representative groups. A second stage provides a detailed analysis of a single representative tile from each group. An Elastic Net classifier produces a diagnostic decision value for each representative tile. A weighted voting scheme aggregates the decision values from these tiles to obtain a diagnosis at the whole slide level. We evaluated our method by automatically classifying 302 brain cancer cases into two possible diagnoses (glioblastoma multiforme (N = 182) versus lower grade glioma (N = 120)) with an accuracy of 93.1% (p Pathology Classification Challenge, in which our method, trained and tested using 5-fold cross validation, produced a classification accuracy of 100% (p < 0.001). Our method showed high stability and robustness to parameter variation, with accuracy varying between 95.5% and 100% when evaluated for a wide range of parameters. Our approach may be useful to automatically differentiate between the two cancer subtypes. Copyright © 2015 Elsevier B.V. All rights

  13. From intracerebral EEG signals to brain connectivity: identification of epileptogenic networks in partial epilepsy.

    Science.gov (United States)

    Wendling, Fabrice; Chauvel, Patrick; Biraben, Arnaud; Bartolomei, Fabrice

    2010-01-01

    Epilepsy is a complex neurological disorder characterized by recurring seizures. In 30% of patients, seizures are insufficiently reduced by anti-epileptic drugs. In the case where seizures originate from a relatively circumscribed region of the brain, epilepsy is said to be partial and surgery can be indicated. The success of epilepsy surgery depends on the accurate localization and delineation of the epileptogenic zone (which often involves several structures), responsible for seizures. It requires a comprehensive pre-surgical evaluation of patients that includes not only imaging data but also long-term monitoring of electrophysiological signals (scalp and intracerebral EEG). During the past decades, considerable effort has been devoted to the development of signal analysis techniques aimed at characterizing the functional connectivity among spatially distributed regions over interictal (outside seizures) or ictal (during seizures) periods from EEG data. Most of these methods rely on the measurement of statistical couplings among signals recorded from distinct brain sites. However, methods differ with respect to underlying theoretical principles (mostly coming from the field of statistics or the field of non-linear physics). The objectives of this paper are: (i) to provide an brief overview of methods aimed at characterizing functional brain connectivity from electrophysiological data, (ii) to provide concrete application examples in the context of drug-refractory partial epilepsies, and iii) to highlight some key points emerging from results obtained both on real intracerebral EEG signals and on signals simulated from physiologically plausible models in which the underlying connectivity patterns are known a priori (ground truth).

  14. Real-time brain activity measurement and signal processing system using highly sensitive MI sensor

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    Kewang Wang

    2017-05-01

    Full Text Available Superconducting Quantum Interference Devices (SQUIDs are the most used sensor to detect the extremely weak magnetic field of brain. However, the sensor heads need to be kept at very low temperature to maintain superconductivity, and that makes the devices large-scale and inconvenient. In order to measure brain activity in normal environment, we had constructed a measurement system based on highly sensitive Magneto-Impedance (MI sensor, and reported the study of measuring Auditory Evoked Field (AEF brain waves. In this study, the system was improved, and the sensor signals can be processed in real-time to monitor brain activity. We use this system to measure the alpha rhythm in the occipital region and the Event-Related Field (ERF P300 in the frontal, the parietal and both the temporal regions.

  15. Real-time brain activity measurement and signal processing system using highly sensitive MI sensor

    Science.gov (United States)

    Wang, Kewang; Cai, Changmei; Yamamoto, Michiharu; Uchiyama, Tsuyoshi

    2017-05-01

    Superconducting Quantum Interference Devices (SQUIDs) are the most used sensor to detect the extremely weak magnetic field of brain. However, the sensor heads need to be kept at very low temperature to maintain superconductivity, and that makes the devices large-scale and inconvenient. In order to measure brain activity in normal environment, we had constructed a measurement system based on highly sensitive Magneto-Impedance (MI) sensor, and reported the study of measuring Auditory Evoked Field (AEF) brain waves. In this study, the system was improved, and the sensor signals can be processed in real-time to monitor brain activity. We use this system to measure the alpha rhythm in the occipital region and the Event-Related Field (ERF) P300 in the frontal, the parietal and both the temporal regions.

  16. Astrocytic Calcium Waves Signal Brain Injury to Neural Stem and Progenitor Cells

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    Anna Kraft

    2017-03-01

    Full Text Available Brain injuries, such as stroke or trauma, induce neural stem cells in the subventricular zone (SVZ to a neurogenic response. Very little is known about the molecular cues that signal tissue damage, even over large distances, to the SVZ. Based on our analysis of gene expression patterns in the SVZ, 48 hr after an ischemic lesion caused by middle cerebral artery occlusion, we hypothesized that the presence of an injury might be transmitted by an astrocytic traveling calcium wave rather than by diffusible factors or hypoxia. Using a newly established in vitro system we show that calcium waves induced in an astrocytic monolayer spread to neural stem and progenitor cells and increase their self-renewal as well as migratory behavior. These changes are due to an upregulation of the Notch signaling pathway. This introduces the concept of propagating astrocytic calcium waves transmitting brain injury signals over long distances.

  17. IMAGING BRAIN SIGNAL TRANSDUCTION AND METABOLISM VIA ARACHIDONIC AND DOCOSAHEXAENOIC ACID IN ANIMALS AND HUMANS

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    Basselin, Mireille; Ramadan, Epolia; Rapoport, Stanley I.

    2012-01-01

    The polyunsaturated fatty acids (PUFAs), arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), important second messengers in brain, are released from membrane phospholipid following receptor-mediated activation of specific phospholipase A2 (PLA2) enzymes. We developed an in vivo method in rodents using quantitative autoradiography to image PUFA incorporation into brain from plasma, and showed that their incorporation rates equal their rates of metabolic consumption by brain. Thus, quantitative imaging of unesterified plasma AA or DHA incorporation into brain can be used as a biomarker of brain PUFA metabolism and neurotransmission. We have employed our method to image and quantify effects of mood stabilizers on brain AA/DHA incorporation during neurotransmission by muscarinic M1,3,5, serotonergic 5-HT2A/2C, dopaminergic D2-like (D2, D3, D4) or glutamatergic N-methyl-D-aspartic acid (NMDA) receptors, and effects of inhibition of acetylcholinesterase, of selective serotonin and dopamine reuptake transporter inhibitors, of neuroinflammation (HIV-1 and lipopolysaccharide) and excitotoxicity, and in genetically modified rodents. The method has been extended for the use with positron emission tomography (PET), and can be employed to determine how human brain AA/DHA signaling and consumption are influenced by diet, aging, disease and genetics. PMID:22178644

  18. Notching on cancer’s door: Notch signaling in brain tumors

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    Marcin eTeodorczyk

    2015-01-01

    Full Text Available Notch receptors play an essential role in the regulation of central cellular processes during embryonic and postnatal development. The mammalian genome encodes for four Notch paralogs (Notch 1-4, which are activated by three Delta-like (Dll1/3/4 and two Serrate-like (Jagged1/2 ligands. Further, non-canonical Notch ligands such as EGFL7 have been identified and serve mostly as antagonists of Notch signaling. The Notch pathway prevents neuronal differentiation in the central nervous system by driving neural stem cell maintenance and commitment of neural progenitor cells into the glial lineage. Notch is therefore often implicated in the development of brain tumors, as tumor cells share various characteristics with neural stem and progenitor cells. Notch receptors are overexpressed in gliomas and their oncogenicity has been confirmed by gain- and loss-of-function studies in vitro and in vivo. To this end, special attention is paid to the impact of Notch signaling on stem-like brain tumor-propagating cells as these cells contribute to growth, survival, invasion and recurrence of brain tumors. Based on the outcome of ongoing studies in vivo, Notch-directed therapies such as γ secretase inhibitors and blocking antibodies have entered and completed various clinical trials. This review summarizes the current knowledge on Notch signaling in brain tumor formation and therapy.

  19. Light-scattering signal may indicate critical time zone to rescue brain tissue after hypoxia

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    Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

    2011-02-01

    A light-scattering signal, which is sensitive to cellular/subcellular structural integrity, is a potential indicator of brain tissue viability because metabolic energy is used in part to maintain the structure of cells. We previously observed a unique triphasic scattering change (TSC) at a certain time after oxygen/glucose deprivation for blood-free rat brains; TSC almost coincided with the cerebral adenosine triphosphate (ATP) depletion. We examine whether such TSC can be observed in the presence of blood in vivo, for which transcranial diffuse reflectance measurement is performed for rat brains during hypoxia induced by nitrogen gas inhalation. At a certain time after hypoxia, diffuse reflectance intensity in the near-infrared region changes in three phases, which is shown by spectroscopic analysis to be due to scattering change in the tissue. During hypoxia, rats are reoxygenated at various time points. When the oxygen supply is started before TSC, all rats survive, whereas no rats survive when the oxygen supply is started after TSC. Survival is probabilistic when the oxygen supply is started during TSC, indicating that the period of TSC can be regarded as a critical time zone for rescuing the brain. The results demonstrate that light scattering signal can be an indicator of brain tissue reversibility.

  20. Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

    Science.gov (United States)

    Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

    2017-03-01

    Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development.

  1. Physiological consequences of membrane-initiated estrogen signaling in the brain

    Science.gov (United States)

    Roepke, Troy A.; Ronnekleiv, Oline K.; Kelly, Martin J.

    2011-01-01

    Many of the actions of 17beta-estradiol (E2) in the central nervous system (CNS) are mediated via the classical nuclear steroid receptors, ERalpha and ERbeta, which interact with the estrogen response element to modulate gene expression. In addition to the nuclear-initiated estrogen signaling, E2 signaling in the brain can occur rapidly within minutes prior to any sufficient effects on transcription of relevant genes. These rapid, membrane-initiated E2 signaling mechanisms have now been characterized in many brain regions, most importantly in neurons of the hypothalamus and hippocampus. Furthermore, our understanding of the physiological effects of membrane-initiated pathways is now a major field of interest in the hypothalamic control of reproduction, energy balance, thermoregulation and other homeostatic functions as well as the effects of E2 on physiological and pathophysiological functions of the hippocampus. Membrane signaling pathways impact neuronal excitability, signal transduction, cell death, neurotransmitter release and gene expression. This review will summarize recent findings on membrane-initiated E2 signaling in the hypothalamus and hippocampus and its contribution to the control of physiological and behavioral functions. PMID:21196248

  2. Structural connectome topology relates to regional BOLD signal dynamics in the mouse brain

    Science.gov (United States)

    Sethi, Sarab S.; Zerbi, Valerio; Wenderoth, Nicole; Fornito, Alex; Fulcher, Ben D.

    2017-04-01

    Brain dynamics are thought to unfold on a network determined by the pattern of axonal connections linking pairs of neuronal elements; the so-called connectome. Prior work has indicated that structural brain connectivity constrains pairwise correlations of brain dynamics ("functional connectivity"), but it is not known whether inter-regional axonal connectivity is related to the intrinsic dynamics of individual brain areas. Here we investigate this relationship using a weighted, directed mesoscale mouse connectome from the Allen Mouse Brain Connectivity Atlas and resting state functional MRI (rs-fMRI) time-series data measured in 184 brain regions in eighteen anesthetized mice. For each brain region, we measured degree, betweenness, and clustering coefficient from weighted and unweighted, and directed and undirected versions of the connectome. We then characterized the univariate rs-fMRI dynamics in each brain region by computing 6930 time-series properties using the time-series analysis toolbox, hctsa. After correcting for regional volume variations, strong and robust correlations between structural connectivity properties and rs-fMRI dynamics were found only when edge weights were accounted for, and were associated with variations in the autocorrelation properties of the rs-fMRI signal. The strongest relationships were found for weighted in-degree, which was positively correlated to the autocorrelation of fMRI time series at time lag τ = 34 s (partial Spearman correlation ρ = 0.58 ), as well as a range of related measures such as relative high frequency power (f > 0.4 Hz: ρ = - 0.43 ). Our results indicate that the topology of inter-regional axonal connections of the mouse brain is closely related to intrinsic, spontaneous dynamics such that regions with a greater aggregate strength of incoming projections display longer timescales of activity fluctuations.

  3. Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response

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    Andreas Stengel

    2017-04-01

    Full Text Available Corticotropin-releasing factor (CRF is the hallmark brain peptide triggering the response to stress and mediates—in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA axis—other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes.

  4. Corticolimbic brain reactivity to social signals of threat before and after sertraline treatment in generalized social phobia.

    Science.gov (United States)

    Phan, K Luan; Coccaro, Emil F; Angstadt, Mike; Kreger, K Jane; Mayberg, Helen S; Liberzon, Israel; Stein, Murray B

    2013-02-15

    Generalized social phobia (gSP), also known as generalized social anxiety disorder, is characterized by excessive fear of scrutiny by others and pervasive avoidance of social interactions. Pathophysiologic models of gSP implicate exaggerated reactivity of the amygdala and insula in response to social evaluative threat, making them plausible targets for treatment. Although selective serotonin reuptake inhibitor (SSRI) treatment is known to be an effective treatment, little is known about the mechanism through which these agents exert their anxiolytic effects at a brain level in gSP. We acquired functional magnetic resonance imaging data of brain response to social signals of threat (fearful/angry faces) in 21 gSP patients before and after they completed 12 weeks of open-label treatment with the SSRI sertraline. For comparison, 19 healthy control (HC) subjects also underwent two functional magnetic resonance imaging scans, 12 weeks apart. Whole-brain voxelwise analysis of variance revealed significant Group×Time interactions in the amygdala and the ventral medial prefrontal cortex. Follow-up analyses showed that treatment in gSP subjects reduced amygdala reactivity to fearful faces (which was exaggerated relative to HCs before treatment) and enhanced ventral medial prefrontal cortex activation to angry faces (which was attenuated relative to HCs before treatment). However, these brain changes were not significantly related to social anxiety symptom improvement. SSRI treatment response in gSP is associated with changes in a discrete limbic-paralimbic brain network, representing a neural mechanism through which SSRIs may exert their actions. Published by Elsevier Inc.

  5. Astaxanthin Alleviates Early Brain Injury Following Subarachnoid Hemorrhage in Rats: Possible Involvement of Akt/Bad Signaling

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    Xiang-Sheng Zhang

    2014-07-01

    Full Text Available Apoptosis has been proven to play a crucial role in early brain injury pathogenesis and to represent a target for the treatment of subarachnoid hemorrhage (SAH. Previously, we demonstrated that astaxanthin (ATX administration markedly reduced neuronal apoptosis in the early period after SAH. However, the underlying molecular mechanisms remain obscure. In the present study, we tried to investigate whether ATX administration is associated with the phosphatidylinositol 3-kinase-Akt (PI3K/Akt pathway, which can play an important role in the signaling of apoptosis. Our results showed that post-SAH treatment with ATX could cause a significant increase of phosphorylated Akt and Bad levels, along with a significant decrease of cleaved caspase-3 levels in the cortex after SAH. In addition to the reduced neuronal apoptosis, treatment with ATX could also significantly reduce secondary brain injury characterized by neurological dysfunction, cerebral edema and blood-brain barrier disruption. In contrast, the PI3K/Akt inhibitor, LY294002, could partially reverse the neuroprotection of ATX in the early period after SAH by downregulating ATX-induced activation of Akt/Bad and upregulating cleaved caspase-3 levels. These results provided the evidence that ATX could attenuate apoptosis in a rat SAH model, potentially, in part, through modulating the Akt/Bad pathway.

  6. Differential maturation of brain signal complexity in the human auditory and visual system

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    Sarah Lippe

    2009-11-01

    Full Text Available Brain development carries with it a large number of structural changes at the local level which impact on the functional interactions of distributed neuronal networks for perceptual processing. Such changes enhance information processing capacity, which can be indexed by estimation of neural signal complexity. Here, we show that during development, EEG signal complexity increases from one month to 5 years of age in response to auditory and visual stimulation. However, the rates of change in complexity were not equivalent for the two responses. Infants’ signal complexity for the visual condition was greater than auditory signal complexity, whereas adults showed the same level of complexity to both types of stimuli. The differential rates of complexity change may reflect a combination of innate and experiential factors on the structure and function of the two sensory systems.

  7. A method for detecting nonlinear determinism in normal and epileptic brain EEG signals.

    Science.gov (United States)

    Meghdadi, Amir H; Fazel-Rezai, Reza; Aghakhani, Yahya

    2007-01-01

    A robust method of detecting determinism for short time series is proposed and applied to both healthy and epileptic EEG signals. The method provides a robust measure of determinism through characterizing the trajectories of the signal components which are obtained through singular value decomposition. Robustness of the method is shown by calculating proposed index of determinism at different levels of white and colored noise added to a simulated chaotic signal. The method is shown to be able to detect determinism at considerably high levels of additive noise. The method is then applied to both intracranial and scalp EEG recordings collected in different data sets for healthy and epileptic brain signals. The results show that for all of the studied EEG data sets there is enough evidence of determinism. The determinism is more significant for intracranial EEG recordings particularly during seizure activity.

  8. mTORC2 activity in brain cancer: Extracellular nutrients are required to maintain oncogenic signaling.

    Science.gov (United States)

    Masui, Kenta; Shibata, Noriyuki; Cavenee, Webster K; Mischel, Paul S

    2016-09-01

    Mutations in growth factor receptor signaling pathways are common in cancer cells, including the highly lethal brain tumor glioblastoma (GBM) where they drive tumor growth through mechanisms including altering the uptake and utilization of nutrients. However, the impact of changes in micro-environmental nutrient levels on oncogenic signaling, tumor growth, and drug resistance is not well understood. We recently tested the hypothesis that external nutrients promote GBM growth and treatment resistance by maintaining the activity of mechanistic target of rapamycin complex 2 (mTORC2), a critical intermediate of growth factor receptor signaling, suggesting that altered cellular metabolism is not only a consequence of oncogenic signaling, but also potentially an important determinant of its activity. Here, we describe the studies that corroborate the hypothesis and propose others that derive from them. Notably, this line of reasoning raises the possibility that systemic metabolism may contribute to responsiveness to targeted cancer therapies. © 2016 WILEY Periodicals, Inc.

  9. Melatonin attenuated brain death tissue extract-induced cardiac damage by suppressing DAMP signaling.

    Science.gov (United States)

    Sung, Pei-Hsun; Lee, Fan-Yen; Lin, Ling-Chun; Chen, Kuan-Hung; Lin, Hung-Sheng; Shao, Pei-Lin; Li, Yi-Chen; Chen, Yi-Ling; Lin, Kun-Chen; Yuen, Chun-Man; Chang, Hsueh-Wen; Lee, Mel S; Yip, Hon-Kan

    2018-01-09

    We tested the hypothesis that melatonin prevents brain death (BD) tissue extract (BDEX)-induced cardiac damage by suppressing inflammatory damage-associated molecular pattern (DAMP) signaling in rats. Six hours after BD induction, levels of a DAMP component (HMGB1) and inflammatory markers (TLR-2, TLR-4, MYD88, IκB, NF-κB, IL-1β, IFN-γ, TNF-α and IL-6) were higher in brain tissue from BD animals than controls. Levels of HMGB1 and inflammatory markers were higher in BDEX-treated H9C2 cardiac myoblasts than in cells treated with healthy brain tissue extract. These increases were attenuated by melatonin but re-induced with luzindole (all P DAMP inflammatory axis.

  10. Neuronal LRP1 regulates glucose metabolism and insulin signaling in the brain.

    Science.gov (United States)

    Liu, Chia-Chen; Hu, Jin; Tsai, Chih-Wei; Yue, Mei; Melrose, Heather L; Kanekiyo, Takahisa; Bu, Guojun

    2015-04-08

    Alzheimer's disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. Accumulating evidence suggests that Type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and glucose intolerance, significantly increases the risk for developing AD. Whereas amyloid-β (Aβ) deposition and neurofibrillary tangles are major histological hallmarks of AD, impairment of cerebral glucose metabolism precedes these pathological changes during the early stage of AD and likely triggers or exacerbates AD pathology. However, the mechanisms linking disturbed insulin signaling/glucose metabolism and AD pathogenesis remain unclear. The low-density lipoprotein receptor-related protein 1 (LRP1), a major apolipoprotein E receptor, plays critical roles in lipoprotein metabolism, synaptic maintenance, and clearance of Aβ in the brain. Here, we demonstrate that LRP1 interacts with the insulin receptor β in the brain and regulates insulin signaling and glucose uptake. LRP1 deficiency in neurons leads to impaired insulin signaling as well as reduced levels of glucose transporters GLUT3 and GLUT4. Consequently, glucose uptake is reduced. By using an in vivo microdialysis technique sampling brain glucose concentration in freely moving mice, we further show that LRP1 deficiency in conditional knock-out mice resulted in glucose intolerance in the brain. We also found that hyperglycemia suppresses LRP1 expression, which further exacerbates insulin resistance, glucose intolerance, and AD pathology. As loss of LRP1 expression is seen in AD brains, our study provides novel insights into insulin resistance in AD. Our work also establishes new targets that can be explored for AD prevention or therapy. Copyright © 2015 the authors 0270-6474/15/355851-09$15.00/0.

  11. Organic bioelectronics for electronic-to-chemical translation in modulation of neuronal signaling and machine-to-brain interfacing.

    Science.gov (United States)

    Larsson, Karin C; Kjäll, Peter; Richter-Dahlfors, Agneta

    2013-09-01

    A major challenge when creating interfaces for the nervous system is to translate between the signal carriers of the nervous system (ions and neurotransmitters) and those of conventional electronics (electrons). Organic conjugated polymers represent a unique class of materials that utilizes both electrons and ions as charge carriers. Based on these materials, we have established a series of novel communication interfaces between electronic components and biological systems. The organic electronic ion pump (OEIP) presented in this review is made of the polymer-polyelectrolyte system poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The OEIP translates electronic signals into electrophoretic migration of ions and neurotransmitters. We demonstrate how spatio-temporally controlled delivery of ions and neurotransmitters can be used to modulate intracellular Ca(2+) signaling in neuronal cells in the absence of convective disturbances. The electronic control of delivery enables strict control of dynamic parameters, such as amplitude and frequency of Ca(2+) responses, and can be used to generate temporal patterns mimicking naturally occurring Ca(2+) oscillations. To enable further control of the ionic signals we developed the electrophoretic chemical transistor, an analog of the traditional transistor used to amplify and/or switch electronic signals. Finally, we demonstrate the use of the OEIP in a new "machine-to-brain" interface by modulating brainstem responses in vivo. This review highlights the potential of communication interfaces based on conjugated polymers in generating complex, high-resolution, signal patterns to control cell physiology. We foresee widespread applications for these devices in biomedical research and in future medical devices within multiple therapeutic areas. This article is part of a Special Issue entitled Organic Bioelectronics-Novel Applications in Biomedicine. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Amplification and propagation of interleukin-1β signaling by murine brain endothelial and glial cells.

    Science.gov (United States)

    Krasnow, Stephanie M; Knoll, J Gabriel; Verghese, Santhosh Chakkaramakkil; Levasseur, Peter R; Marks, Daniel L

    2017-07-01

    During acute infections and chronic illnesses, the pro-inflammatory cytokine interleukin-1β (IL-1β) acts within the brain to elicit metabolic derangements and sickness behaviors. It is unknown which cells in the brain are the proximal targets for IL-1β with respect to the generation of these illness responses. We performed a series of in vitro experiments to (1) investigate which brain cell populations exhibit inflammatory responses to IL-1β and (2) examine the interactions between different IL-1β-responsive cell types in various co-culture combinations. We treated primary cultures of murine brain microvessel endothelial cells (BMEC), astrocytes, and microglia with PBS or IL-1β, and then performed qPCR to measure inflammatory gene expression or immunocytochemistry to evaluate nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. To evaluate whether astrocytes and/or BMEC propagate inflammatory signals to microglia, we exposed microglia to astrocyte-conditioned media and co-cultured endothelial cells and glia in transwells. Treatment groups were compared by Student's t tests or by ANOVA followed by Bonferroni-corrected t tests. IL-1β increased inflammatory gene expression and NF-κB activation in primary murine-mixed glia, enriched astrocyte, and BMEC cultures. Although IL-1β elicited minimal changes in inflammatory gene expression and did not induce the nuclear translocation of NF-κB in isolated microglia, these cells were more robustly activated by IL-1β when co-cultured with astrocytes and/or BMEC. We observed a polarized endothelial response to IL-1β, because the application of IL-1β to the abluminal endothelial surface produced a more complex microglial inflammatory response than that which occurred following luminal IL-1β exposure. Inflammatory signals are detected, amplified, and propagated through the CNS via a sequential and reverberating signaling cascade involving communication between brain endothelial cells and

  13. P2X7 Receptor Signaling Contributes to Sepsis-Associated Brain Dysfunction.

    Science.gov (United States)

    Savio, Luiz Eduardo Baggio; Andrade, Mariana G Juste; de Andrade Mello, Paola; Santana, Patrícia Teixeira; Moreira-Souza, Aline Cristina Abreu; Kolling, Janaína; Longoni, Aline; Feldbrügge, Linda; Wu, Yan; Wyse, Angela T S; Robson, Simon C; Coutinho-Silva, Robson

    2017-10-01

    Sepsis results in unfettered inflammation, tissue damage, and multiple organ failure. Diffuse brain dysfunction and neurological manifestations secondary to sepsis are termed sepsis-associated encephalopathy (SAE). Extracellular nucleotides, proinflammatory cytokines, and oxidative stress reactions are associated with delirium and brain injury, and might be linked to the pathophysiology of SAE. P2X7 receptor activation by extracellular ATP leads to maturation and release of IL-1β by immune cells, which stimulates the production of oxygen reactive species. Hence, we sought to investigate the role of purinergic signaling by P2X7 in a model of sepsis. We also determined how this process is regulated by the ectonucleotidase CD39, a scavenger of extracellular nucleotides. Wild type (WT), P2X7 receptor (P2X7-/-), or CD39 (CD39-/-) deficient mice underwent sham laparotomy or CLP induced by ligation and puncture of the cecum. We noted that genetic deletion of P2X7 receptor decreased markers of oxidative stress in murine brains 24 h after sepsis induction. The pharmacological inhibition or genetic ablation of the P2X7 receptor attenuated the IL-1β and IL-6 production in the brain from septic mice. Furthermore, our results suggest a crucial role for the enzyme CD39 in limiting P2X7 receptor proinflammatory responses since CD39-/- septic mice exhibited higher levels of IL-1β in the brain. We have also demonstrated that P2X7 receptor blockade diminished STAT3 activation in cerebral cortex and hippocampus from septic mice, indicating association of ATP-P2X7-STAT3 signaling axis in SAE during sepsis. Our findings suggest that P2X7 receptor might serve as a suitable therapeutic target to ameliorate brain damage in sepsis.

  14. Assessing signal-driven mechanism in neonates: brain responses to temporally and spectrally different sounds

    Directory of Open Access Journals (Sweden)

    Yasuyo eMinagawa-Kawai

    2011-06-01

    Full Text Available Past studies have found that in adults that acoustic properties of sound signals (such as fast vs. slow temporal features differentially activate the left and right hemispheres, and some have hypothesized that left-lateralization for speech processing may follow from left-lateralization to rapidly changing signals. Here, we tested whether newborns’ brains show some evidence of signal-specific lateralization responses using near-infrared spectroscopy (NIRS and auditory stimuli that elicits lateralized responses in adults, composed of segments that vary in duration and spectral diversity. We found significantly greater bilateral responses of oxygenated hemoglobin (oxy-Hb in the temporal areas for stimuli with a minimum segment duration of 21 ms, than stimuli with a minimum segment duration of 667 ms. However, we found no evidence for hemispheric asymmetries dependent on the stimulus characteristics. We hypothesize that acoustic-based functional brain asymmetries may develop throughout early infancy, and discuss their possible relationship with brain asymmetries for language.

  15. From intracerebral EEG signals to brain connectivity: identification of epileptogenic networks in partial epilepsy

    Directory of Open Access Journals (Sweden)

    Fabrice Wendling

    2010-11-01

    Full Text Available Epilepsy is a complex neurological disorder characterized by recurring seizures. In 30% of patients, seizures are insufficiently reduced by anti-epileptic drugs. In the case where seizures originate from a relatively circumscribed region of the brain, epilepsy is said to be partial and surgery can be indicated. The success of epilepsy surgery depends on the accurate localisation and delineation of the epileptogenic zone (which often involves several structures, responsible for seizures. It requires a comprehensive pre-surgical evaluation of patients that includes not only imaging data but also long-term monitoring of electrophysiological signals (scalp and intracerebral EEG. During the past decades, considerable effort has been devoted to the development of signal analysis techniques aimed at characterizing the functional connectivity among spatially-distributed regions over interictal (outside seizures or ictal (during seizures periods from EEG data. Most of these methods rely on the measurement of statistical couplings among signals recorded from distinct brain sites. However, methods differ with respect to underlying theoretical principles (mostly coming from the field of statistics or the field of nonlinear physics. The objectives of this paper are: i to provide an brief overview of methods aimed at characterizing functional brain connectivity from electrophysiological data, ii to provide concrete application examples in the context of drug-refractory partial epilepsies, and iii to highlight some key points emerging from results obtained both on real intracerebral EEG signals and on signals simulated from physiologically-plausible models in which the underlying connectivity patterns are known a priori (ground truth.

  16. Fractal analysis of spontaneous fluctuations of the BOLD signal in the human brain networks.

    Science.gov (United States)

    Li, Yi-Chia; Huang, Yun-An

    2014-05-01

    To investigate what extent brain regions are continuously interacting during resting-state, independent component analyses (ICA) was applied to analyze resting-state functional MRI (RS-fMRI) data. According to the analyzed results, it was surprisingly found that low frequency fluctuations (LFFs), which belong to the 1/f signal (a signal with power spectrum whose power spectral density is inversely proportional to the frequency), have been classified into groups using ICA; furthermore, the spatial distributions of these groups within the brain were found to resemble the spatial distributions of different networks, which manifests that the signal characteristics of RS LFFs are distinct across networks. In our work, we applied the 1/f model in the fractal analyses to further investigate this distinction. Twenty healthy participants got involved in this study. They were scanned to acquire the RS-fMRI data. The acquired data were first processed with ICA to obtain the networks of the resting brain. Afterward, the blood-oxygenation level dependent (BOLD) signals of these networks were processed with the fractal analyses for obtaining the fractal parameter α. α was found to significantly vary across networks, which reveals that the fractal characteristic of LFFs differs across networks. According to prior literatures, this difference could be brought by the discrepancy of hemodynamic response amplitude (HRA) between networks. Hence, in our work, we also performed the computational simulation to discover the relationship between α and HRA. Based on the simulation results, HRA is highly linear-correlated with the fractal characteristics of LFFs which is revealed by α. Our results support that the origin of RS-fMRI signals contains arterial fluctuations. Hence, in addition to the commonly used method such as synchrony analysis and power spectral analysis, another approach, the fractal analysis, is suggested for acquiring the information of hemodynamic responses by means

  17. Study on Brain Dynamics by Non Linear Analysis of Music Induced EEG Signals

    Science.gov (United States)

    Banerjee, Archi; Sanyal, Shankha; Patranabis, Anirban; Banerjee, Kaushik; Guhathakurta, Tarit; Sengupta, Ranjan; Ghosh, Dipak; Ghose, Partha

    2016-02-01

    Music has been proven to be a valuable tool for the understanding of human cognition, human emotion, and their underlying brain mechanisms. The objective of this study is to analyze the effect of Hindustani music on brain activity during normal relaxing conditions using electroencephalography (EEG). Ten male healthy subjects without special musical education participated in the study. EEG signals were acquired at the frontal (F3/F4) lobes of the brain while listening to music at three experimental conditions (rest, with music and without music). Frequency analysis was done for the alpha, theta and gamma brain rhythms. The finding shows that arousal based activities were enhanced while listening to Hindustani music of contrasting emotions (romantic/sorrow) for all the subjects in case of alpha frequency bands while no significant changes were observed in gamma and theta frequency ranges. It has been observed that when the music stimulus is removed, arousal activities as evident from alpha brain rhythms remain for some time, showing residual arousal. This is analogous to the conventional 'Hysteresis' loop where the system retains some 'memory' of the former state. This is corroborated in the non linear analysis (Detrended Fluctuation Analysis) of the alpha rhythms as manifested in values of fractal dimension. After an input of music conveying contrast emotions, withdrawal of music shows more retention as evidenced by the values of fractal dimension.

  18. Comparative analysis of brain EEG signals generated from the right and left hand while writing

    Science.gov (United States)

    Sardesai, Neha; Jamali Mahabadi, S. E.; Meng, Qinglei; Choa, Fow-Sen

    2016-05-01

    This paper provides a comparative analysis of right handed people and left handed people when they write with both their hands. Two left handed and one right handed subject were asked to write their respective names on a paper using both, their left and right handed, and their brain signals were measured using EEG. Similarly, they were asked to perform simple mathematical calculations using both their hand. The data collected from the EEG from writing with both hands is compared. It is observed that though it is expected that the right brain only would contribute to left handed writing and vice versa, it is not so. When a right handed person writes with his/her left hand, the initial instinct is to go for writing with the right hand. Hence, both parts of the brain are active when a subject writes with the other hand. However, when the activity is repeated, the brain learns to expect to write with the other hand as the activity is repeated and then only the expected part of the brain is active.

  19. The interaction between alpha 7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α represents a new antinociceptive signaling pathway in mice.

    Science.gov (United States)

    Donvito, Giulia; Bagdas, Deniz; Toma, Wisam; Rahimpour, Elnaz; Jackson, Asti; Meade, Julie A; AlSharari, Shakir; Kulkarni, Abhijit R; Ivy Carroll, F; Lichtman, Aron H; Papke, Roger L; Thakur, Ganesh A; Imad Damaj, M

    2017-09-01

    Recently, α7 nicotinic acetylcholine receptors (nAChRs), primarily activated by binding of orthosteric agonists, represent a target for anti-inflammatory and analgesic drug development. These receptors may also be modulated by positive allosteric modulators (PAMs), ago-allosteric ligands (ago-PAMs), and α7-silent agonists. Activation of α7 nAChRs has been reported to increase the brain levels of endogenous ligands for nuclear peroxisome proliferator-activated receptors type-α (PPAR-α), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), in a Ca2+-dependent manner. Here, we investigated potential crosstalk between α7 nAChR and PPAR-α, using the formalin test, a mouse model of tonic pain. Using pharmacological and genetic approaches, we found that PNU282987, a full α7 agonist, attenuated formalin-induced nociceptive behavior in α7-dependent manner. Interestingly, the selective PPAR-α antagonist GW6471 blocked the antinociceptive effects of PNU282987, but did not alter the antinociceptive responses evoked by the α7 nAChR PAM PNU120596, ago-PAM GAT107, and silent agonist NS6740. Moreover, GW6471 administered systemically or spinally, but not via the intraplantar surface of the formalin-injected paw blocked PNU282987-induced antinociception. Conversely, exogenous administration of the naturally occurring PPAR-α agonist PEA potentiated the antinociceptive effects of PNU282987. In contrast, the cannabinoid CB1 antagonist rimonabant and the CB2 antagonist SR144528 failed to reverse the antinociceptive effects of PNU282987. These findings suggest that PPAR-α plays a key role in a putative antinociceptive α7 nicotinic signaling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Fast attainment of computer cursor control with noninvasively acquired brain signals

    Science.gov (United States)

    Bradberry, Trent J.; Gentili, Rodolphe J.; Contreras-Vidal, José L.

    2011-06-01

    Brain-computer interface (BCI) systems are allowing humans and non-human primates to drive prosthetic devices such as computer cursors and artificial arms with just their thoughts. Invasive BCI systems acquire neural signals with intracranial or subdural electrodes, while noninvasive BCI systems typically acquire neural signals with scalp electroencephalography (EEG). Some drawbacks of invasive BCI systems are the inherent risks of surgery and gradual degradation of signal integrity. A limitation of noninvasive BCI systems for two-dimensional control of a cursor, in particular those based on sensorimotor rhythms, is the lengthy training time required by users to achieve satisfactory performance. Here we describe a novel approach to continuously decoding imagined movements from EEG signals in a BCI experiment with reduced training time. We demonstrate that, using our noninvasive BCI system and observational learning, subjects were able to accomplish two-dimensional control of a cursor with performance levels comparable to those of invasive BCI systems. Compared to other studies of noninvasive BCI systems, training time was substantially reduced, requiring only a single session of decoder calibration (~20 min) and subject practice (~20 min). In addition, we used standardized low-resolution brain electromagnetic tomography to reveal that the neural sources that encoded observed cursor movement may implicate a human mirror neuron system. These findings offer the potential to continuously control complex devices such as robotic arms with one's mind without lengthy training or surgery.

  1. Distinguishing low frequency oscillations within the 1/f spectral behaviour of electromagnetic brain signals

    Directory of Open Access Journals (Sweden)

    Sonuga-Barke Edmund JS

    2007-12-01

    Full Text Available Abstract Background It has been acknowledged that the frequency spectrum of measured electromagnetic (EM brain signals shows a decrease in power with increasing frequency. This spectral behaviour may lead to difficulty in distinguishing event-related peaks from ongoing brain activity in the electro- and magnetoencephalographic (EEG and MEG signal spectra. This can become an issue especially in the analysis of low frequency oscillations (LFOs – below 0.5 Hz – which are currently being observed in signal recordings linked with specific pathologies such as epileptic seizures or attention deficit hyperactivity disorder (ADHD, in sleep studies, etc. Methods In this work we propose a simple method that can be used to compensate for this 1/f trend hence achieving spectral normalisation. This method involves filtering the raw measured EM signal through a differentiator prior to further data analysis. Results Applying the proposed method to various exemplary datasets including very low frequency EEG recordings, epileptic seizure recordings, MEG data and Evoked Response data showed that this compensating procedure provides a flat spectral base onto which event related peaks can be clearly observed. Conclusion Findings suggest that the proposed filter is a useful tool for the analysis of physiological data especially in revealing very low frequency peaks which may otherwise be obscured by the 1/f spectral activity inherent in EEG/MEG recordings.

  2. Signalling through the Type 1 Insulin-Like Growth Factor Receptor (IGF1R Interacts with Canonical Wnt Signalling to Promote Neural Proliferation in Developing Brain

    Directory of Open Access Journals (Sweden)

    Qichen Hu

    2012-05-01

    Full Text Available Signalling through the IGF1R [type 1 IGF (insulin-like growth factor receptor] and canonical Wnt signalling are two signalling pathways that play critical roles in regulating neural cell generation and growth. To determine whether the signalling through the IGF1R can interact with the canonical Wnt signalling pathway in neural cells in vivo, we studied mutant mice with altered IGF signalling. We found that in mice with blunted IGF1R expression specifically in nestin-expressing neural cells (IGF1RNestin–KO mice the abundance of neural β-catenin was significantly reduced. Blunting IGF1R expression also markedly decreased: (i the activity of a LacZ (β-galactosidase reporter transgene that responds to Wnt nuclear signalling (LacZTCF reporter transgene and (ii the number of proliferating neural precursors. In contrast, overexpressing IGF-I (insulin-like growth factor I in brain markedly increased the activity of the LacZTCF reporter transgene. Consistently, IGF-I treatment also markedly increased the activity of the LacZTCF reporter transgene in embryonic neuron cultures that are derived from LacZTCF Tg (transgenic mice. Importantly, increasing the abundance of β-catenin in IGF1RNestin–KO embryonic brains by suppressing the activity of GSK3β (glycogen synthase kinase-3β significantly alleviated the phenotypic changes induced by IGF1R deficiency. These phenotypic changes includes: (i retarded brain growth, (ii reduced precursor proliferation and (iii decreased neuronal number. Our current data, consistent with our previous study of cultured oligodendrocytes, strongly support the concept that IGF signalling interacts with canonical Wnt signalling in the developing brain to promote neural proliferation. The interaction of IGF and canonical Wnt signalling plays an important role in normal brain development by promoting neural precursor proliferation.

  3. Expression Profiling of Autism Candidate Genes during Human Brain Development Implicates Central Immune Signaling Pathways

    OpenAIRE

    Ziats, Mark N.; Rennert, Owen M.

    2011-01-01

    The Autism Spectrum Disorders (ASD) represent a clinically heterogeneous set of conditions with strong hereditary components. Despite substantial efforts to uncover the genetic basis of ASD, the genomic etiology appears complex and a clear understanding of the molecular mechanisms underlying Autism remains elusive. We hypothesized that focusing gene interaction networks on ASD-implicated genes that are highly expressed in the developing brain may reveal core mechanisms that are otherwise obsc...

  4. Altered Wnt signalling in the teenage suicide brain: focus on glycogen synthase kinase-3β and β-catenin

    National Research Council Canada - National Science Library

    Ren, Xinguo; Rizavi, Hooriyah S; Khan, Mansoor A; Dwivedi, Yogesh; Pandey, Ghanshyam N

    2013-01-01

    Glycogen synthase kinase (GSK)-3β and β-catenin are important components of the Wnt signalling pathway, which is involved in numerous physiological functions such as cognition, brain development and cell survival...

  5. Altered Wnt signalling in the teenage suicide brain: focus on glycogen synthase kinase-3[beta] and [beta]-catenin

    National Research Council Canada - National Science Library

    Xinguo Ren; Hooriyah S Rizavi; Mansoor A Khan; Yogesh Dwivedi; Ghanshyam N Pandey

    2013-01-01

      Abstract Glycogen synthase kinase (GSK)-3[beta] and [beta]-catenin are important components of the Wnt signalling pathway, which is involved in numerous physiological functions such as cognition, brain development and cell survival...

  6. Histone deacetylases control neurogenesis in embryonic brain by inhibition of BMP2/4 signaling.

    Directory of Open Access Journals (Sweden)

    Maya Shakèd

    Full Text Available BACKGROUND: Histone-modifying enzymes are essential for a wide variety of cellular processes dependent upon changes in gene expression. Histone deacetylases (HDACs lead to the compaction of chromatin and subsequent silencing of gene transcription, and they have recently been implicated in a diversity of functions and dysfunctions in the postnatal and adult brain including ocular dominance plasticity, memory consolidation, drug addiction, and depression. Here we investigate the role of HDACs in the generation of neurons and astrocytes in the embryonic brain. PRINCIPAL FINDINGS: As a variety of HDACs are expressed in differentiating neural progenitor cells, we have taken a pharmacological approach to inhibit multiple family members. Inhibition of class I and II HDACs in developing mouse embryos with trichostatin A resulted in a dramatic reduction in neurogenesis in the ganglionic eminences and a modest increase in neurogenesis in the cortex. An identical effect was observed upon pharmacological inhibition of HDACs in in vitro-differentiating neural precursors derived from the same brain regions. A reduction in neurogenesis in ganglionic eminence-derived neural precursors was accompanied by an increase in the production of immature astrocytes. We show that HDACs control neurogenesis by inhibition of the bone morphogenetic protein BMP2/4 signaling pathway in radial glial cells. HDACs function at the transcriptional level by inhibiting and promoting, respectively, the expression of Bmp2 and Smad7, an intracellular inhibitor of BMP signaling. Inhibition of the BMP2/4 signaling pathway restored normal levels of neurogenesis and astrogliogenesis to both ganglionic eminence- and cortex-derived cultures in which HDACs were inhibited. CONCLUSIONS: Our results demonstrate a transcriptionally-based regulation of BMP2/4 signaling by HDACs both in vivo and in vitro that is critical for neurogenesis in the ganglionic eminences and that modulates cortical

  7. Adipocyte Glucocorticoid Receptors Mediate Fat-To-Brain Signaling Short Title: Adipocyte GR Mediate Fat-To-Brain Feedback

    Science.gov (United States)

    de Kloet, Annette D.; Krause, Eric G.; Solomon, Matia B.; Flak, Jonathan N.; Scott, Karen A.; Kim, Dong-Hoon; Myers, Brent; Ulrich-Lai, Yvonne M.; Woods, Stephen C.; Seeley, Randy J.; Herman, James P.

    2015-01-01

    Stress-related (e.g., depression) and metabolic pathologies (e.g., obesity) are important and often co-morbid public health concerns. Here we identify a connection between peripheral glucocorticoid receptor (GR) signaling originating in fat with the brain control of both stress and metabolism. Mice with reduced adipocyte GR hypersecrete glucocorticoids following acute psychogenic stress and are resistant to diet-induced obesity. This hypersecretion gives rise to deficits in responsiveness to exogenous glucocorticoids, consistent with reduced negative feedback via adipocytes. Increased stress reactivity occurs in the context of elevated hypothalamic expression of hypothalamic-pituitary-adrenal (HPA) axis-excitatory neuropeptides and in the absence of altered adrenal sensitivity, consistent with a central cite of action. Our results identify a novel mechanism whereby activation of the adipocyte GR promotes peripheral energy storage while inhibiting the HPA axis, and provide functional evidence for a fat-to-brain regulatory feedback network that serves to regulate not just homeostatic energy balance but also responses to psychogenic stimuli. PMID:25808702

  8. Quantification of ethanol methyl 1H magnetic resonance signal intensity following intravenous ethanol administration in primate brain

    OpenAIRE

    Flory, Graham S.; O’Malley, Jean; Grant, Kathleen A.; Park, Byung; Kroenke, Christopher D.

    2009-01-01

    In vivo 1H magnetic resonance spectroscopy (MRS) can be used to directly monitor brain ethanol. Previously, studies of human subjects have lead to the suggestion that the ethanol methyl 1H MRS signal intensity relates to tolerance to ethanol’s intoxicating effects. More recently, the ethanol 1H MRS signal intensity has been recognized to vary between brain gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) due to differences in T2 within these environments. The methods present...

  9. Early Life Experience and Gut Microbiome: the Brain-Gut-Microbiota Signaling System

    Science.gov (United States)

    Cong, Xiaomei; Henderson, Wendy A.; Graf, Joerg; McGrath, Jacqueline M.

    2015-01-01

    Background Over the past decades, advances in neonatal care have led to substantial increases in survival among preterm infants. With these gains, recent concerns have focused on increases in neurodevelopment morbidity related to the interplay between stressful early life experiences and the immature neuro-immune systems. This interplay between these complex mechanisms is often described as the brain-gut signaling system. The role of the gut microbiome and the brain-gut signaling system have been found to be remarkably related to both short and long term stress and health. Recent evidence supports that microbial species, ligands, and/or products within the developing intestine play a key role in early programming of the central nervous system and regulation of the intestinal innate immunity. Purpose The purpose of this state-of-the-science review is to explore the supporting evidence demonstrating the importance of the brain-gut-microbiota axis in regulation of early life experience. We also discuss the role of gut microbiome in modulating stress and pain responses in high-risk infants. A conceptual framework has been developed to illustrate the regulation mechanisms involved in early life experience. Conclusions The science in this area is just beginning to be uncovered; having a fundamental understanding of these relationships will be important as new discoveries continue to change our thinking; leading potentially to changes in practice and targeted interventions. PMID:26240939

  10. CD73 is a major regulator of adenosinergic signalling in mouse brain.

    Directory of Open Access Journals (Sweden)

    Natalia Kulesskaya

    Full Text Available CD73 (ecto-5'-nucleotidase is a cell surface enzyme that regulates purinergic signalling by desphosphorylating extracellular AMP to adenosine. 5'-nucleotidases are known to be expressed in brain, but the expression of CD73 and its putative physiological functions at this location remain elusive. Here we found, using immunohistochemistry of wild-type and CD73 deficient mice, that CD73 is prominently expressed in the basal ganglia core comprised of striatum (caudate nucleus and putamen and globus pallidus. Furthermore, meninges and the olfactory tubercle were found to specifically express CD73. Analysis of wild type (wt and CD73 deficient mice revealed that CD73 confers the majority of 5'-nucleotidase activity in several areas of the brain. In a battery of behavioural tests and in IntelliCage studies, the CD73 deficient mice demonstrated significantly enhanced exploratory locomotor activity, which probably reflects the prominent expression of CD73 in striatum and globus pallidus that are known to control locomotion. Furthermore, the CD73 deficient mice displayed altered social behaviour. Overall, our data provide a novel mechanistic insight into adenosinergic signalling in brain, which is implicated in the regulation of normal and pathological behaviour.

  11. Hand posture classification using electrocorticography signals in the gamma band over human sensorimotor brain areas

    Science.gov (United States)

    Chestek, Cynthia A.; Gilja, Vikash; Blabe, Christine H.; Foster, Brett L.; Shenoy, Krishna V.; Parvizi, Josef; Henderson, Jaimie M.

    2013-04-01

    Objective. Brain-machine interface systems translate recorded neural signals into command signals for assistive technology. In individuals with upper limb amputation or cervical spinal cord injury, the restoration of a useful hand grasp could significantly improve daily function. We sought to determine if electrocorticographic (ECoG) signals contain sufficient information to select among multiple hand postures for a prosthetic hand, orthotic, or functional electrical stimulation system.Approach. We recorded ECoG signals from subdural macro- and microelectrodes implanted in motor areas of three participants who were undergoing inpatient monitoring for diagnosis and treatment of intractable epilepsy. Participants performed five distinct isometric hand postures, as well as four distinct finger movements. Several control experiments were attempted in order to remove sensory information from the classification results. Online experiments were performed with two participants. Main results. Classification rates were 68%, 84% and 81% for correct identification of 5 isometric hand postures offline. Using 3 potential controls for removing sensory signals, error rates were approximately doubled on average (2.1×). A similar increase in errors (2.6×) was noted when the participant was asked to make simultaneous wrist movements along with the hand postures. In online experiments, fist versus rest was successfully classified on 97% of trials; the classification output drove a prosthetic hand. Online classification performance for a larger number of hand postures remained above chance, but substantially below offline performance. In addition, the long integration windows used would preclude the use of decoded signals for control of a BCI system. Significance. These results suggest that ECoG is a plausible source of command signals for prosthetic grasp selection. Overall, avenues remain for improvement through better electrode designs and placement, better participant training

  12. Quorum Sensing Signal Synthesis May Represent a Selective Advantage Independent of Its Role in Regulation of Bioluminescence in Vibrio fischeri.

    Directory of Open Access Journals (Sweden)

    Grace Chong

    Full Text Available The evolution of biological signalling systems and apparently altruistic or cooperative traits in diverse organisms has required selection against the subversive tendencies of self-interested biological entities. The bacterial signalling and response system known as quorum sensing or Acylated Homoserine Lactone (AHL mediated gene expression is thought to have evolved through kin selection. In this in vitro study on the model quorum sensing bioluminescent marine symbiont Vibrio fischeri, competition and long-term sub culturing experiments suggest that selection for AHL synthesis (encoded by the AHL synthase gene luxI is independent of the quorum sensing regulated phenotype (bioluminescence encoded by luxCDABE. Whilst results support the hypothesis that signal response (AHL binding and transcriptional activation encoded by the luxR gene is maintained through indirect fitness benefits (kin selection, signal synthesis is maintained in the V. fischeri genome over evolutionary time through direct fitness benefits at the individual level from an unknown function.

  13. Quorum Sensing Signal Synthesis May Represent a Selective Advantage Independent of Its Role in Regulation of Bioluminescence in Vibrio fischeri

    Science.gov (United States)

    Chong, Grace; Kimyon, Önder; Manefield, Mike

    2013-01-01

    The evolution of biological signalling systems and apparently altruistic or cooperative traits in diverse organisms has required selection against the subversive tendencies of self-interested biological entities. The bacterial signalling and response system known as quorum sensing or Acylated Homoserine Lactone (AHL) mediated gene expression is thought to have evolved through kin selection. In this in vitro study on the model quorum sensing bioluminescent marine symbiont Vibrio fischeri, competition and long-term sub culturing experiments suggest that selection for AHL synthesis (encoded by the AHL synthase gene luxI) is independent of the quorum sensing regulated phenotype (bioluminescence encoded by luxCDABE). Whilst results support the hypothesis that signal response (AHL binding and transcriptional activation encoded by the luxR gene) is maintained through indirect fitness benefits (kin selection), signal synthesis is maintained in the V. fischeri genome over evolutionary time through direct fitness benefits at the individual level from an unknown function. PMID:23825662

  14. The system of cerebrospinal fluid-contacting neurons. Its supposed role in the nonsynaptic signal transmission of the brain.

    Science.gov (United States)

    Vígh, B; Manzano e Silva, M J; Frank, C L; Vincze, C; Czirok, S J; Szabó, A; Lukáts, A; Szél, A

    2004-04-01

    attached by half-desmosomes on the basal lamina of the external and vascular surface of the brain tissue. Therefore, the bioactive materials released from these terminals primarily enter the external CSF and secondarily, by diffusion into vessels and the composition of the external CSF, may have a modulatory effect on the bioactive substances released by the neurohormonal terminals. Contacting the intercellular space, sensory-type cilia were also demonstrated on nerve cells situated subependymally or farther away from the ventricles, among others in the neurosecretory nuclei. Since tight-junctions are lacking between ependymal cells of the ventricular wall, not only CSF-contacting but also subependymal ciliated neurons may be influenced by the actual composition of the CSF besides that of the intercellular fluid of the brain tissue. According to the comparative histological data summarised in this review, the ventricular CSF-contacting neurons represent the phylogenetically oldest component detecting the internal fluid milieu of the brain. The neurohormonal terminals on the external surface of the brain equally represent an ancient form of nonsynaptic signal transmission.

  15. Cannabinoid Signaling and Neuroinflammatory Diseases: A Melting pot for the Regulation of Brain Immune Responses.

    Science.gov (United States)

    Chiurchiù, Valerio; Leuti, Alessandro; Maccarrone, Mauro

    2015-06-01

    The concept of the central nervous system (CNS) as an immune-privileged site, essentially due to the presence of the blood brain barrier, appears to be overly simplistic. Indeed, within healthy CNS immune activities are permitted and are required for neuronal function and host defense, not only due to the presence of the resident innate immune cells of the brain, but also by virtue of a complex cross-talk of the CNS with peripheral immune cells. Nonetheless, long-standing and persisting neuroinflammatory responses are most often detrimental and characterize several neuroinflammatory diseases, including multiple sclerosis, Alzheimer's disease and amyotrophic lateral sclerosis. A growing body of evidence suggests that Cannabis sativa-derived phytocannabinoids, as well as synthetic cannabinoids, are endowed with significant immunoregulatory and anti-inflammatory properties, both in peripheral tissues and in the CNS, through the activation of cannabinoid receptors. In this review, the immunomodulatory effects of cannabinoid signaling on the most relevant brain immune cells will be discussed. In addition, the impact of cannabinoid regulation on the overall integration of the manifold brain immune responses will also be highlighted, along with the implication of these compounds as potential agents for the management of neuroinflammatory disorders.

  16. Astrocytic Calcium Waves Signal Brain Injury to Neural Stem and Progenitor Cells.

    Science.gov (United States)

    Kraft, Anna; Jubal, Eduardo Rosales; von Laer, Ruth; Döring, Claudia; Rocha, Adriana; Grebbin, Moyo; Zenke, Martin; Kettenmann, Helmut; Stroh, Albrecht; Momma, Stefan

    2017-03-14

    Brain injuries, such as stroke or trauma, induce neural stem cells in the subventricular zone (SVZ) to a neurogenic response. Very little is known about the molecular cues that signal tissue damage, even over large distances, to the SVZ. Based on our analysis of gene expression patterns in the SVZ, 48 hr after an ischemic lesion caused by middle cerebral artery occlusion, we hypothesized that the presence of an injury might be transmitted by an astrocytic traveling calcium wave rather than by diffusible factors or hypoxia. Using a newly established in vitro system we show that calcium waves induced in an astrocytic monolayer spread to neural stem and progenitor cells and increase their self-renewal as well as migratory behavior. These changes are due to an upregulation of the Notch signaling pathway. This introduces the concept of propagating astrocytic calcium waves transmitting brain injury signals over long distances. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. A guide to delineate the logic of neurovascular signaling in the brain

    Directory of Open Access Journals (Sweden)

    David eKleinfeld

    2011-04-01

    Full Text Available The neurovascular system may be viewed as a distributed nervous system within the brain. It transforms local neuronal activity into a change in the tone of smooth muscle that lines the walls of arterioles and microvessels. We review the current state of neurovascular coupling, with an emphasis on signaling molecules that convey information from neurons to neighboring vessels. At the level of neocortex, this coupling is mediated by: (i a likely direct interaction with inhibitory neurons, (ii indirect interaction, via astrocytes, with excitatory neurons, and (iii fiber tracts from subcortical layers. Substantial evidence shows that control involves competition between signals that promote vasoconstriction versus vasodilation. Consistent with this picture is evidence that, under certain circumstances, increased neuronal activity can lead to vasoconstriction rather than vasodilation. This confounds naïve interpretations of functional brain images. We discuss experimental approaches to detect signaling molecules in vivo with the goal of formulating an empirical basis for the observed logic of neurovascular control.

  18. Quantitative evaluation of linear and nonlinear methods characterizing interdependencies between brain signals.

    Science.gov (United States)

    Ansari-Asl, Karim; Senhadji, Lotfi; Bellanger, Jean-Jacques; Wendling, Fabrice

    2006-09-01

    Brain functional connectivity can be characterized by the temporal evolution of correlation between signals recorded from spatially-distributed regions. It is aimed at explaining how different brain areas interact within networks involved during normal (as in cognitive tasks) or pathological (as in epilepsy) situations. Numerous techniques were introduced for assessing this connectivity. Recently, some efforts were made to compare methods performances but mainly qualitatively and for a special application. In this paper, we go further and propose a comprehensive comparison of different classes of methods (linear and nonlinear regressions, phase synchronization, and generalized synchronization) based on various simulation models. For this purpose, quantitative criteria are used: in addition to mean square error under null hypothesis (independence between two signals) and mean variance computed over all values of coupling degree in each model, we provide a criterion for comparing performances. Results show that the performances of the compared methods are highly dependent on the hypothesis regarding the underlying model for the generation of the signals. Moreover, none of them outperforms the others in all cases and the performance hierarchy is model dependent.

  19. Reelin signaling in the migration of ventral brain stem and spinal cord neurons

    Directory of Open Access Journals (Sweden)

    Sandra eBlaess

    2016-03-01

    Full Text Available The extracellular matrix protein Reelin is an important orchestrator of neuronal migration during the development of the central nervous system. While its role and mechanism of action have been extensively studied and reviewed in the formation of dorsal laminar brain structures like the cerebral cortex, hippocampus, and cerebellum, its functions during the neuronal migration events that result in the nuclear organization of the ventral central nervous system are less well understood. In an attempt to delineate an underlying pattern of Reelin action in the formation of neuronal cell clusters, this review highlights the role of Reelin signaling in the migration of neuronal populations that originate in the ventral brain stem and the spinal cord.

  20. Lactate-mediated glia-neuronal signalling in the mammalian brain

    Science.gov (United States)

    Tang, F.; Lane, S.; Korsak, A.; Paton, J. F. R.; Gourine, A. V.; Kasparov, S.; Teschemacher, A. G.

    2014-02-01

    Astrocytes produce and release L-lactate as a potential source of energy for neurons. Here we present evidence that L-lactate, independently of its caloric value, serves as an astrocytic signalling molecule in the locus coeruleus (LC). The LC is the principal source of norepinephrine to the frontal brain and thus one of the most influential modulatory centers of the brain. Optogenetically activated astrocytes release L-lactate, which excites LC neurons and triggers release of norepinephrine. Exogenous L-lactate within the physiologically relevant concentration range mimics these effects. L-lactate effects are concentration-dependent, stereo-selective, independent of L-lactate uptake into neurons and involve a cAMP-mediated step. In vivo injections of L-lactate in the LC evokes arousal similar to the excitatory transmitter, L-glutamate. Our results imply the existence of an unknown receptor for this ‘glio-transmitter’.

  1. Toll-like receptor 2 signaling in response to brain injury: an innate bridge to neuroinflammation

    DEFF Research Database (Denmark)

    Babcock, Alicia; Wirenfeldt, Martin; Holm, Thomas

    2006-01-01

    -induced expression of cytokines and chemokines. Recruitment of T cells, but not macrophages, was delayed in TLR2-deficient mice, as well as in mice lacking TNFR1 (tumor necrosis factor receptor 1). TLR2 deficiency also affected microglial proliferative expansion, whereas all of these events were unaffected in TLR4......-mutant mice. Consistent with the fact that responses in knock-out mice had all returned to wild-type levels by 8 d, there was no evidence for effects on neuronal plasticity at 20 d. These results identify a role for TLR2 signaling in the early glial response to brain injury, acting as an innate bridge...

  2. [Music-Acoustic Signals Controlled by Subject's Brain Potentials in the Correction of Unfavorable Functional States].

    Science.gov (United States)

    Fedotchev, A I; Bondar, A T; Bakhchina, A V; Parin, S B; Polevaya, S A; Radchenko, G S

    2016-01-01

    Literature review and the results of own studies on the development and experimental testing of musical EEG neurofeedback technology are presented. The technology is based on exposure of subjects to music or music-like signals that are organized in strict accordance with the current values of brain potentials of the patient. The main attention is paid to the analysis of the effectiveness of several versions of the technology, using specific and meaningful for the individual narrow-frequency EEG oscillators during the correction of unfavorable changes of the functional state.

  3. Alteration of brain insulin and leptin signaling promotes energy homeostasis impairment and neurodegenerative diseases

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    Taouis Mohammed

    2011-09-01

    Full Text Available The central nervous system (CNS controls vital functions, by efficiently coordinating peripheral and central cascades of signals and networks in a coordinated manner. Historically, the brain was considered to be an insulin-insensitive tissue. But, new findings demonstrating that insulin is present in different regions of themammalian brain, in particular the hypothalamus and the hippocampus. Insulin acts through specific receptors and dialogues with numerous peptides, neurotransmitters and adipokines such as leptin. The cross-talk between leptin and insulin signaling pathways at the hypothalamic level is clearly involved in the control of energy homeostasis. Both hormones are anorexigenic through their action on hypothalamic arcuate nucleus by inducing the expression of anorexigenic neuropetides such as POMC (pro-opiomelanocortin, the precursor of aMSH and reducing the expression of orexigenic neuropeptide such as NPY (Neuropeptide Y. Central defect of insulin and leptin signaling predispose to obesity (leptin-resistant state and type-2 diabetes (insulin resistant state. Obesity and type-2 diabetes are associated to deep alterations in energy homeostasis control but also to other alterations of CNS functions as the predisposition to neurodegenerative diseases such as Alzheimer’s disease (AD. AD is a neurodegenerative disorder characterized by distinct hallmarks within the brain. Postmortem observation of AD brains showed the presence of parenchymal plaques due to the accumulation of the amyloid beta (AB peptide and neurofibrillary tangles. These accumulations result from the hyperphosphorylation of tau (a mictrotubule-interacting protein. Both insulin and leptin have been described to modulate tau phosphorylation and therefore in leptin and insulin resistant states may contribute to AD. The concentrations of leptin and insulin cerebrospinal fluid are decreased type2 diabetes and obese patients. In addition, the concentration of insulin in the

  4. Restoring susceptibility induced MRI signal loss in rat brain at 9.4 T: A step towards whole brain functional connectivity imaging.

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    Rupeng Li

    Full Text Available The aural cavity magnetic susceptibility artifact leads to significant echo planar imaging (EPI signal dropout in rat deep brain that limits acquisition of functional connectivity fcMRI data. In this study, we provide a method that recovers much of the EPI signal in deep brain. Needle puncture introduction of a liquid-phase fluorocarbon into the middle ear allows acquisition of rat fcMRI data without signal dropout. We demonstrate that with seeds chosen from previously unavailable areas, including the amygdala and the insular cortex, we are able to acquire large scale networks, including the limbic system. This tool allows EPI-based neuroscience and pharmaceutical research in rat brain using fcMRI that was previously not feasible.

  5. Alternate day fasting impacts the brain insulin-signaling pathway of young adult male C57BL/6 mice.

    Science.gov (United States)

    Lu, Jianghua; E, Lezi; Wang, Wenfang; Frontera, Jennifer; Zhu, Hao; Wang, Wen-Tung; Lee, Phil; Choi, In Young; Brooks, William M; Burns, Jeffrey M; Aires, Daniel; Swerdlow, Russell H

    2011-04-01

    Dietary restriction (DR) has recognized health benefits that may extend to brain. We examined how DR affects bioenergetics-relevant enzymes and signaling pathways in the brains of C57BL/6 mice. Five-month-old male mice were placed in ad libitum or one of two repeated fasting and refeeding (RFR) groups, an alternate day (intermittent fed; IF) or alternate day plus antioxidants (blueberry, pomegranate, and green tea extracts) (IF + AO) fed group. During the 24-h fast blood glucose levels initially fell but stabilized within 6 h of starting the fast, thus avoiding frank hypoglycemia. DR in general appeared to enhance insulin sensitivity. After six weeks brain AKT and glycogen synthase kinase 3 beta phosphorylation were lower in the RFR mice, suggesting RFR reduced brain insulin-signaling pathway activity. Pathways that mediate mitochondrial biogenesis were not activated; AMP kinase phosphorylation, silent information regulator 2 phosphorylation, peroxisomal proliferator-activated receptor-gamma coactivator 1 alpha levels, and cytochrome oxidase subunit 4 levels did not change. ATP levels also did not decline, which suggests the RFR protocols did not directly impact brain bioenergetics. Antioxidant supplementation did not affect the brain parameters we evaluated. Our data indicate in young adult male C57BL/6 mice, RFR primarily affects brain energy metabolism by reducing brain insulin signaling, which potentially results indirectly as a consequence of reduced peripheral insulin production. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  6. Selection of independent components representing event-related brain potentials: A data-driven approach for greater objectivity

    NARCIS (Netherlands)

    Wessel, J.R.; Ullsperger, M.

    2011-01-01

    Following the development of increasingly precise measurement instruments and fine-grain analysis tools for electroencephalographic (EEG) data, analysis of single-trial event-related EEG has considerably widened the utility of this non-invasive method to investigate brain activity. Recently,

  7. Task-dependent signal variations in EEG error-related potentials for brain-computer interfaces

    Science.gov (United States)

    Iturrate, I.; Montesano, L.; Minguez, J.

    2013-04-01

    Objective. A major difficulty of brain-computer interface (BCI) technology is dealing with the noise of EEG and its signal variations. Previous works studied time-dependent non-stationarities for BCIs in which the user’s mental task was independent of the device operation (e.g., the mental task was motor imagery and the operational task was a speller). However, there are some BCIs, such as those based on error-related potentials, where the mental and operational tasks are dependent (e.g., the mental task is to assess the device action and the operational task is the device action itself). The dependence between the mental task and the device operation could introduce a new source of signal variations when the operational task changes, which has not been studied yet. The aim of this study is to analyse task-dependent signal variations and their effect on EEG error-related potentials.Approach. The work analyses the EEG variations on the three design steps of BCIs: an electrophysiology study to characterize the existence of these variations, a feature distribution analysis and a single-trial classification analysis to measure the impact on the final BCI performance.Results and significance. The results demonstrate that a change in the operational task produces variations in the potentials, even when EEG activity exclusively originated in brain areas related to error processing is considered. Consequently, the extracted features from the signals vary, and a classifier trained with one operational task presents a significant loss of performance for other tasks, requiring calibration or adaptation for each new task. In addition, a new calibration for each of the studied tasks rapidly outperforms adaptive techniques designed in the literature to mitigate the EEG time-dependent non-stationarities.

  8. Protease activated receptor signaling is required for African trypanosome traversal of human brain microvascular endothelial cells.

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    Dennis J Grab

    2009-07-01

    Full Text Available Using human brain microvascular endothelial cells (HBMECs as an in vitro model for how African trypanosomes cross the human blood-brain barrier (BBB we recently reported that the parasites cross the BBB by generating calcium activation signals in HBMECs through the activity of parasite cysteine proteases, particularly cathepsin L (brucipain. In the current study, we examined the possible role of a class of protease stimulated HBMEC G protein coupled receptors (GPCRs known as protease activated receptors (PARs that might be implicated in calcium signaling by African trypanosomes.Using RNA interference (RNAi we found that in vitro PAR-2 gene (F2RL1 expression in HBMEC monolayers could be reduced by over 95%. We also found that the ability of Trypanosoma brucei rhodesiense to cross F2RL1-silenced HBMEC monolayers was reduced (39%-49% and that HBMECs silenced for F2RL1 maintained control levels of barrier function in the presence of the parasite. Consistent with the role of PAR-2, we found that HBMEC barrier function was also maintained after blockade of Galpha(q with Pasteurella multocida toxin (PMT. PAR-2 signaling has been shown in other systems to have neuroinflammatory and neuroprotective roles and our data implicate a role for proteases (i.e. brucipain and PAR-2 in African trypanosome/HBMEC interactions. Using gene-profiling methods to interrogate candidate HBMEC pathways specifically triggered by brucipain, several pathways that potentially link some pathophysiologic processes associated with CNS HAT were identified.Together, the data support a role, in part, for GPCRs as molecular targets for parasite proteases that lead to the activation of Galpha(q-mediated calcium signaling. The consequence of these events is predicted to be increased permeability of the BBB to parasite transmigration and the initiation of neuroinflammation, events precursory to CNS disease.

  9. Brain processing of visual stimuli representing sexual penetration versus core and animal-reminder disgust in women with lifelong vaginismus.

    Science.gov (United States)

    Borg, Charmaine; Georgiadis, Janniko R; Renken, Remco J; Spoelstra, Symen K; Weijmar Schultz, Willibrord; de Jong, Peter J

    2014-01-01

    It has been proposed that disgust evolved to protect humans from contamination. Through eliciting the overwhelming urge to withdraw from the disgusting stimuli, it would facilitate avoidance of contact with pathogens. The physical proximity implied in sexual intercourse provides ample opportunity for contamination and may thus set the stage for eliciting pathogen disgust. Building on this, it has been argued that the involuntary muscle contraction characteristic of vaginismus (i.e., inability to have vaginal penetration) may be elicited by the prospect of penetration by potential contaminants. To further investigate this disgust-based interpretation of vaginismus (in DSM-5 classified as a Genito-Pelvic Pain/Penetration Disorder, GPPPD) we used functional magnetic resonance imaging (fMRI) to examine if women with vaginismus (n = 21) show relatively strong convergence in their brain responses towards sexual penetration- and disgust-related pictures compared to sexually asymptomatic women (n = 21) and women suffering from vulvar pain (dyspareunia/also classified as GPPPD in the DSM-5, n = 21). At the subjective level, both clinical groups rated penetration stimuli as more disgusting than asymptomatic women. However, the brain responses to penetration stimuli did not differ between groups. In addition, there was considerable conjoint brain activity in response to penetration and disgust pictures, which yield for both animal-reminder (e.g., mutilation) and core (e.g., rotten food) disgust domains. However, this overlap in brain activation was similar for all groups. A possible explanation for the lack of vaginismus-specific brain responses lies in the alleged female ambiguity (procreation/pleasure vs. contamination/disgust) toward penetration: generally in women a (default) disgust response tendency may prevail in the absence of sexual readiness. Accordingly, a critical next step would be to examine the processing of penetration stimuli following the

  10. Brain processing of visual stimuli representing sexual penetration versus core and animal-reminder disgust in women with lifelong vaginismus.

    Directory of Open Access Journals (Sweden)

    Charmaine Borg

    Full Text Available It has been proposed that disgust evolved to protect humans from contamination. Through eliciting the overwhelming urge to withdraw from the disgusting stimuli, it would facilitate avoidance of contact with pathogens. The physical proximity implied in sexual intercourse provides ample opportunity for contamination and may thus set the stage for eliciting pathogen disgust. Building on this, it has been argued that the involuntary muscle contraction characteristic of vaginismus (i.e., inability to have vaginal penetration may be elicited by the prospect of penetration by potential contaminants. To further investigate this disgust-based interpretation of vaginismus (in DSM-5 classified as a Genito-Pelvic Pain/Penetration Disorder, GPPPD we used functional magnetic resonance imaging (fMRI to examine if women with vaginismus (n = 21 show relatively strong convergence in their brain responses towards sexual penetration- and disgust-related pictures compared to sexually asymptomatic women (n = 21 and women suffering from vulvar pain (dyspareunia/also classified as GPPPD in the DSM-5, n = 21. At the subjective level, both clinical groups rated penetration stimuli as more disgusting than asymptomatic women. However, the brain responses to penetration stimuli did not differ between groups. In addition, there was considerable conjoint brain activity in response to penetration and disgust pictures, which yield for both animal-reminder (e.g., mutilation and core (e.g., rotten food disgust domains. However, this overlap in brain activation was similar for all groups. A possible explanation for the lack of vaginismus-specific brain responses lies in the alleged female ambiguity (procreation/pleasure vs. contamination/disgust toward penetration: generally in women a (default disgust response tendency may prevail in the absence of sexual readiness. Accordingly, a critical next step would be to examine the processing of penetration stimuli following

  11. Alternative functions of the brain transsulfuration pathway represent an underappreciated aspect of brain redox biochemistry with significant potential for therapeutic engagement.

    Science.gov (United States)

    Hensley, Kenneth; Denton, Travis T

    2015-01-01

    Scientific appreciation for the subtlety of brain sulfur chemistry has lagged, despite understanding that the brain must maintain high glutathione (GSH) to protect against oxidative stress in tissue that has both a high rate of oxidative respiration and a high content of oxidation-prone polyunsaturated fatty acids. In fact, the brain was long thought to lack a complete transsulfuration pathway (TSP) for cysteine synthesis. It is now clear that not only does the brain possess a functional TSP, but brain TSP enzymes catalyze a rich array of alternative reactions that generate novel species including the gasotransmitter hydrogen sulfide (H2S) and the atypical amino acid lanthionine (Lan). Moreover, TSP intermediates can be converted to unusual cyclic ketimines via transamination. Cell-penetrating derivatives of one such compound, lanthionine ketimine (LK), have potent antioxidant, neuroprotective, neurotrophic, and antineuroinflammatory actions and mitigate diverse neurodegenerative conditions in preclinical rodent models. This review will explore the source and function of alternative TSP products, and lanthionine-derived metabolites in particular. The known biological origins of lanthionine and its ketimine metabolite will be described in detail and placed in context with recent discoveries of a GSH- and LK-binding brain protein called LanCL1 that is proving essential for neuronal antioxidant defense; and a related LanCL2 homolog now implicated in immune sensing and cell fate determinations. The review will explore possible endogenous functions of lanthionine metabolites and will discuss the therapeutic potential of lanthionine ketimine derivatives for mitigating diverse neurological conditions including Alzheimer׳s disease, stroke, motor neuron disease, and glioma. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Quantitative Analysis of Diffusion Weighted MR Images of Brain Tumor Using Signal Intensity Gradient Technique

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    S. S. Shanbhag

    2014-01-01

    Full Text Available The purpose of this study was to evaluate the role of diffusion weighted-magnetic resonance imaging (DW-MRI in the examination and classification of brain tumors, namely, glioma and meningioma. Our hypothesis was that as signal intensity variations on diffusion weighted (DW images depend on histology and cellularity of the tumor, analysing the signal intensity characteristics on DW images may allow differentiating between the tumor types. Towards this end the signal intensity variations on DW images of the entire tumor volume data of 20 subjects with glioma and 12 subjects with meningioma were investigated and quantified using signal intensity gradient (SIG parameter. The relative increase in the SIG values (RSIG for the subjects with glioma and meningioma was in the range of 10.08–28.36 times and 5.60–9.86 times, respectively, compared to their corresponding SIG values on the contralateral hemisphere. The RSIG values were significantly different between the subjects with glioma and meningioma (P<0.01, with no overlap between RSIG values across the two tumors. The results indicate that the quantitative changes in the RSIG values could be applied in the differential diagnosis of glioma and meningioma, and their adoption in clinical diagnosis and treatment could be helpful and informative.

  13. AMPA receptor-induced local brain-derived neurotrophic factor signaling mediates motor recovery after stroke.

    Science.gov (United States)

    Clarkson, Andrew N; Overman, Justine J; Zhong, Sheng; Mueller, Rudolf; Lynch, Gary; Carmichael, S Thomas

    2011-03-09

    Stroke is the leading cause of adult disability. Recovery after stroke shares similar molecular and cellular properties with learning and memory. A main component of learning-induced plasticity involves signaling through AMPA receptors (AMPARs). We systematically tested the role of AMPAR function in motor recovery in a mouse model of focal stroke. AMPAR function controls functional recovery beginning 5 d after the stroke. Positive allosteric modulators of AMPARs enhance recovery of limb control when administered after a delay from the stroke. Conversely, AMPAR antagonists impair motor recovery. The contributions of AMPARs to recovery are mediated by release of brain-derived neurotrophic factor (BDNF) in periinfarct cortex, as blocking local BDNF function in periinfarct cortex blocks AMPAR-mediated recovery and prevents the normal pattern of motor recovery. In contrast to a delayed AMPAR role in motor recovery, early administration of AMPAR agonists after stroke increases stroke damage. These findings indicate that the role of glutamate signaling through the AMPAR changes over time in stroke: early potentiation of AMPAR signaling worsens stroke damage, whereas later potentiation of the same signaling system improves functional recovery.

  14. Sex differences in brain-derived neurotrophic factor signaling and functions.

    Science.gov (United States)

    Chan, Chi Bun; Ye, Keqiang

    2017-01-02

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family that plays a critical role in numerous neuronal activities. Recent studies have indicated that some functions or action mechanisms of BDNF vary in a sex-dependent manner. In particular, BDNF content in some brain parts and the tendency to develop BDNF deficiency-related diseases such as depression are greater in female animals. With the support of relevant studies, it has been suggested that sex hormones or steroids can modulate the activities of BDNF, which may account for its functional discrepancy in different sexes. Indeed, the cross-talk between BDNF and sex steroids has been detected for decades, and some sex steroids, such as estrogen, have a positive regulatory effect on BDNF expression and signaling. Thus, the sex of animal models that are used in studying the functions of BDNF is critical. This Mini-Review summarizes our current findings on the differences in expression, signaling, and functions of BDNF between sexes. We also discuss the potential mechanisms for mediating these differential responses, with a specific emphasis on sex steroids. By presenting and discussing these findings, we seek to encourage researchers to take sex influences into consideration when designing experiments, interpreting results, and drawing conclusions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. BrainSignals Revisited: Simplifying a Computational Model of Cerebral Physiology.

    Directory of Open Access Journals (Sweden)

    Matthew Caldwell

    Full Text Available Multimodal monitoring of brain state is important both for the investigation of healthy cerebral physiology and to inform clinical decision making in conditions of injury and disease. Near-infrared spectroscopy is an instrument modality that allows non-invasive measurement of several physiological variables of clinical interest, notably haemoglobin oxygenation and the redox state of the metabolic enzyme cytochrome c oxidase. Interpreting such measurements requires the integration of multiple signals from different sources to try to understand the physiological states giving rise to them. We have previously published several computational models to assist with such interpretation. Like many models in the realm of Systems Biology, these are complex and dependent on many parameters that can be difficult or impossible to measure precisely. Taking one such model, BrainSignals, as a starting point, we have developed several variant models in which specific regions of complexity are substituted with much simpler linear approximations. We demonstrate that model behaviour can be maintained whilst achieving a significant reduction in complexity, provided that the linearity assumptions hold. The simplified models have been tested for applicability with simulated data and experimental data from healthy adults undergoing a hypercapnia challenge, but relevance to different physiological and pathophysiological conditions will require specific testing. In conditions where the simplified models are applicable, their greater efficiency has potential to allow their use at the bedside to help interpret clinical data in near real-time.

  16. When the brain simulates stopping: Neural activity recorded during real and imagined stop-signal tasks.

    Science.gov (United States)

    González-Villar, Alberto J; Bonilla, F Mauricio; Carrillo-de-la-Peña, María T

    2016-10-01

    It has been suggested that mental rehearsal activates brain areas similar to those activated by real performance. Although inhibition is a key function of human behavior, there are no previous reports of brain activity during imagined response cancellation. We analyzed event-related potentials (ERPs) and time-frequency data associated with motor execution and inhibition during real and imagined performance of a stop-signal task. The ERPs characteristic of stop trials-that is, the stop-N2 and stop-P3-were also observed during covert performance of the task. Imagined stop (IS) trials yielded smaller stop-N2 amplitudes than did successful stop (SS) and unsuccessful stop (US) trials, but midfrontal theta power similar to that in SS trials. The stop-P3 amplitude for IS was intermediate between those observed for SS and US. The results may be explained by the absence of error-processing and correction processes during imagined performance. For go trials, real execution was associated with higher mu and beta desynchronization over motor areas, which confirms previous reports of lower motor activation during imagined execution and also with larger P3b amplitudes, probably indicating increased top-down attention to the real task. The similar patterns of activity observed for imagined and real performance suggest that imagination tasks may be useful for training inhibitory processes. Nevertheless, brain activation was generally weaker during mental rehearsal, probably as a result of the reduced engagement of top-down mechanisms and limited error processing.

  17. Ablation of Type-1 IFN Signaling in Hematopoietic Cells Confers Protection Following Traumatic Brain Injury.

    Science.gov (United States)

    Karve, Ila P; Zhang, Moses; Habgood, Mark; Frugier, Tony; Brody, Kate M; Sashindranath, Maithili; Ek, C Joakim; Chappaz, Stephane; Kile, Ben T; Wright, David; Wang, Hong; Johnston, Leigh; Daglas, Maria; Ates, Robert C; Medcalf, Robert L; Taylor, Juliet M; Crack, Peter J

    2016-01-01

    Type-1 interferons (IFNs) are pleiotropic cytokines that signal through the type-1 IFN receptor (IFNAR1). Recent literature has implicated the type-1 IFNs in disorders of the CNS. In this study, we have investigated the role of type-1 IFNs in neuroinflammation following traumatic brain injury (TBI). Using a controlled cortical impact model, TBI was induced in 8- to 10-week-old male C57BL/6J WT and IFNAR1(-/-) mice and brains were excised to study infarct volume, inflammatory mediator release via quantitative PCR analysis and immune cell profile via immunohistochemistry. IFNAR1(-/-) mice displayed smaller infarcts compared with WT mice after TBI. IFNAR1(-/-) mice exhibited an altered anti-inflammatory environment compared with WT mice, with significantly reduced levels of the proinflammatory mediators TNFα, IL-1β and IL-6, an up-regulation of the anti-inflammatory mediator IL-10 and an increased activation of resident and peripheral immune cells after TBI. WT mice injected intravenously with an anti-IFNAR1 blocking monoclonal antibody (MAR1) 1 h before, 30 min after or 30 min and 2 d after TBI displayed significantly improved histological and behavioral outcome. Bone marrow chimeras demonstrated that the hematopoietic cells are a peripheral source of type-1 IFNs that drives neuroinflammation and a worsened TBI outcome. Type-1 IFN mRNA levels were confirmed to be significantly altered in human postmortem TBI brains. Together, these data demonstrate that type-1 IFN signaling is a critical pathway in the progression of neuroinflammation and presents a viable therapeutic target for the treatment of TBI.

  18. Ablation of Type-1 IFN Signaling in Hematopoietic Cells Confers Protection Following Traumatic Brain Injury123

    Science.gov (United States)

    Karve, Ila P.; Zhang, Moses; Habgood, Mark; Frugier, Tony; Brody, Kate M.; Sashindranath, Maithili; Ek, C. Joakim; Kile, Ben T.; Wright, David; Wang, Hong; Johnston, Leigh; Daglas, Maria; Ates, Robert C.; Medcalf, Robert L.; Taylor, Juliet M.

    2016-01-01

    Abstract Type-1 interferons (IFNs) are pleiotropic cytokines that signal through the type-1 IFN receptor (IFNAR1). Recent literature has implicated the type-1 IFNs in disorders of the CNS. In this study, we have investigated the role of type-1 IFNs in neuroinflammation following traumatic brain injury (TBI). Using a controlled cortical impact model, TBI was induced in 8- to 10-week-old male C57BL/6J WT and IFNAR1−/− mice and brains were excised to study infarct volume, inflammatory mediator release via quantitative PCR analysis and immune cell profile via immunohistochemistry. IFNAR1−/− mice displayed smaller infarcts compared with WT mice after TBI. IFNAR1−/− mice exhibited an altered anti-inflammatory environment compared with WT mice, with significantly reduced levels of the proinflammatory mediators TNFα, IL-1β and IL-6, an up-regulation of the anti-inflammatory mediator IL-10 and an increased activation of resident and peripheral immune cells after TBI. WT mice injected intravenously with an anti-IFNAR1 blocking monoclonal antibody (MAR1) 1 h before, 30 min after or 30 min and 2 d after TBI displayed significantly improved histological and behavioral outcome. Bone marrow chimeras demonstrated that the hematopoietic cells are a peripheral source of type-1 IFNs that drives neuroinflammation and a worsened TBI outcome. Type-1 IFN mRNA levels were confirmed to be significantly altered in human postmortem TBI brains. Together, these data demonstrate that type-1 IFN signaling is a critical pathway in the progression of neuroinflammation and presents a viable therapeutic target for the treatment of TBI. PMID:27022620

  19. Linking EEG signals, brain functions and mental operations: Advantages of the Laplacian transformation.

    Science.gov (United States)

    Vidal, Franck; Burle, Boris; Spieser, Laure; Carbonnell, Laurence; Meckler, Cédric; Casini, Laurence; Hasbroucq, Thierry

    2015-09-01

    Electroencephalography (EEG) is a very popular technique for investigating brain functions and/or mental processes. To this aim, EEG activities must be interpreted in terms of brain and/or mental processes. EEG signals being a direct manifestation of neuronal activity it is often assumed that such interpretations are quite obvious or, at least, straightforward. However, they often rely on (explicit or even implicit) assumptions regarding the structures supposed to generate the EEG activities of interest. For these assumptions to be used appropriately, reliable links between EEG activities and the underlying brain structures must be established. Because of volume conduction effects and the mixture of activities they induce, these links are difficult to establish with scalp potential recordings. We present different examples showing how the Laplacian transformation, acting as an efficient source separation method, allowed to establish more reliable links between EEG activities and brain generators and, ultimately, with mental operations. The nature of those links depends on the depth of inferences that can vary from weak to strong. Along this continuum, we show that 1) while the effects of experimental manipulation can appear widely distributed with scalp potentials, Laplacian transformation allows to reveal several generators contributing (in different manners) to these modulations, 2) amplitude variations within the same set of generators can generate spurious differences in scalp potential topographies, often interpreted as reflecting different source configurations. In such a case, Laplacian transformation provides much more similar topographies, evidencing the same generator(s) set, and 3) using the LRP as an index of response activation most often produces ambiguous results, Laplacian-transformed response-locked ERPs obtained over motor areas allow resolving these ambiguities. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Apo-ghrelin receptor (apo-GHSR1a Regulates Dopamine Signaling in the Brain

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    Andras eKern

    2014-08-01

    Full Text Available The orexigenic peptide hormone ghrelin is synthesized in the stomach and its receptor growth hormone secretagogue receptor (GHSR1a is expressed mainly in the central nervous system (CNS. In this review we confine our discussion to the physiological role of GHSR1a in the brain. Paradoxically, despite broad expression of GHSR1a in the CNS, other than trace amounts in the hypothalamus, ghrelin is undetectable in the brain. In our efforts to elucidate the function of the ligand-free ghrelin receptor (apo-GHSR1a we identified subsets of neurons that co-express GHSR1a and dopamine receptors. In this review we focus on interactions between apo-GHSR1a and dopamine-2 receptor (DRD2 and formation of GHSR1a:DRD2 heteromers in hypothalamic neurons that regulate appetite, and discuss implications for the treatment of Prader-Willi syndrome. GHSR1a antagonists of distinct chemical structures, a quinazolinone and a triazole, respectively enhance and inhibit dopamine signaling through GHSR1a:DRD2 heteromers by an allosteric mechanism. This finding illustrates a potential strategy for designing the next generation of drugs for treating eating disorders as well as psychiatric disorders caused by abnormal dopamine signaling. Treatment with a GHSR1a antagonist that enhances dopamine/DRD2 activity in GHSR1a:DRD2 expressing hypothalamic neurons has the potential to inhibit the uncontrollable hyperphagia associated with Prader-Willi syndrome. DRD2 antagonists are prescribed for treating schizophrenia, but these block dopamine signaling in all DRD2 expressing neurons and are associated with adverse side effects, including enhanced appetite and excessive weight gain. A GHSR1a antagonist of structural class that allosterically blocks dopamine/DRD2 action in GHSR1a:DRD2 expressing neurons would have no effect on neurons expressing DRD2 alone; therefore, the side effects of DRD2 antagonists would potentially be reduced thereby enhancing patient compliance.

  1. Brain insulin signalling in the regulation of energy balance and peripheral metabolism.

    Science.gov (United States)

    Diamant, Michaela

    2007-03-30

    The unparalleled global rates of obesity and type 2 diabetes, together with the associated cardiovascular morbidity and mortality, are referred to as the "diabesity pandemic". Changes in lifestyle occurring worldwide, including the increased consumption of high-caloric foods and reduced exercise, are regarded as the main causal factors. Central obesity and insulin resistance have emerged as important linking components. Understanding the aetiology of the cluster of pathologies that leads to the increased risk is instrumental in the development of preventive and therapeutic strategies. Historically, skeletal muscle, adipose tissue and liver were regarded as key insulin target organs involved in insulin-mediated regulation of peripheral carbohydrate, lipid and protein metabolism. The consequences of impaired insulin action in these organs were deemed to explain the functional and structural abnormalities associated with insulin resistance. The discovery of insulin receptors in the central nervous system, the detection of insulin in the cerebrospinal fluid after peripheral insulin administration and the well-documented effects of intracerebroventricularly injected insulin on energy homeostasis, have identified the brain as an important target for insulin action. In addition to its critical role as a peripheral signal integrating the complex network of hypothalamic neuropeptides and neurotransmitters that influence parameters of energy balance, central nervous insulin signalling is also implicated in the regulation of peripheral glucose metabolism. This review summarizes the evidence of insulin action in the brain as part of the multifaceted circuit involved in the central regulation of energy and glucose homeostasis, and discuss the role of impaired central nervous insulin signalling as a pathogenic factor in the obesity and type 2 diabetes epidemic.

  2. Monoaminergic integration of diet and social signals in the brains of juvenile spadefoot toads.

    Science.gov (United States)

    Burmeister, Sabrina S; Rodriguez Moncalvo, Verónica G; Pfennig, Karin S

    2017-09-01

    Social behavior often includes the production of species-specific signals (e.g. mating calls or visual displays) that evoke context-dependent behavioral responses from conspecifics. Monoamines are important neuromodulators that have been implicated in context-dependent social behavior, yet we know little about the development of monoaminergic systems and whether they mediate the effects of early life experiences on adult behavior. We examined the effects of diet and social signals on monoamines early in development in the plains spadefoot toad (Spea bombifrons), a species in which diet affects the developmental emergence of species recognition and body condition affects the expression of adult mating preferences. To do so, we manipulated the diet of juveniles for 6 weeks following metamorphosis and collected their brains 40 min following the presentation of either a conspecific or a heterospecific call. We measured levels of monoamines and their metabolites using high pressure liquid chromatography from tissue punches of the auditory midbrain (i.e. torus semicircularis), hypothalamus and preoptic area. We found that call type affected dopamine and noradrenaline signaling in the auditory midbrain and that diet affected dopamine and serotonin in the hypothalamus. In the preoptic area, we detected an interaction between diet and call type, indicating that diet modulates how the preoptic area integrates social information. Our results suggest that the responsiveness of monoamine systems varies across the brain and highlight preoptic dopamine and noradrenaline as candidates for mediating effects of early diet experience on later expression of social preferences. © 2017. Published by The Company of Biologists Ltd.

  3. Prefrontal Neurons Represent Motion Signals from Across the Visual Field But for Memory-Guided Comparisons Depend on Neurons Providing These Signals.

    Science.gov (United States)

    Wimmer, Klaus; Spinelli, Philip; Pasternak, Tatiana

    2016-09-07

    Visual decisions often involve comparisons of sequential stimuli that can appear at any location in the visual field. The lateral prefrontal cortex (LPFC) in nonhuman primates, shown to play an important role in such comparisons, receives information about contralateral stimuli directly from sensory neurons in the same hemisphere, and about ipsilateral stimuli indirectly from neurons in the opposite hemisphere. This asymmetry of sensory inputs into the LPFC poses the question of whether and how its neurons incorporate sensory information arriving from the two hemispheres during memory-guided comparisons of visual motion. We found that, although responses of individual LPFC neurons to contralateral stimuli were stronger and emerged 40 ms earlier, they carried remarkably similar signals about motion direction in the two hemifields, with comparable direction selectivity and similar direction preferences. This similarity was also apparent around the time of the comparison between the current and remembered stimulus because both ipsilateral and contralateral responses showed similar signals reflecting the remembered direction. However, despite availability in the LPFC of motion information from across the visual field, these "comparison effects" required for the comparison stimuli to appear at the same retinal location. This strict dependence on spatial overlap of the comparison stimuli suggests participation of neurons with localized receptive fields in the comparison process. These results suggest that while LPFC incorporates many key aspects of the information arriving from sensory neurons residing in opposite hemispheres, it continues relying on the interactions with these neurons at the time of generating signals leading to successful perceptual decisions. Visual decisions often involve comparisons of sequential visual motion that can appear at any location in the visual field. We show that during such comparisons, the lateral prefrontal cortex (LPFC) contains

  4. Genome-wide identification of Bcl11b gene targets reveals role in brain-derived neurotrophic factor signaling.

    Directory of Open Access Journals (Sweden)

    Bin Tang

    Full Text Available B-cell leukemia/lymphoma 11B (Bcl11b is a transcription factor showing predominant expression in the striatum. To date, there are no known gene targets of Bcl11b in the nervous system. Here, we define targets for Bcl11b in striatal cells by performing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq in combination with genome-wide expression profiling. Transcriptome-wide analysis revealed that 694 genes were significantly altered in striatal cells over-expressing Bcl11b, including genes showing striatal-enriched expression similar to Bcl11b. ChIP-seq analysis demonstrated that Bcl11b bound a mixture of coding and non-coding sequences that were within 10 kb of the transcription start site of an annotated gene. Integrating all ChIP-seq hits with the microarray expression data, 248 direct targets of Bcl11b were identified. Functional analysis on the integrated gene target list identified several zinc-finger encoding genes as Bcl11b targets, and further revealed a significant association of Bcl11b to brain-derived neurotrophic factor/neurotrophin signaling. Analysis of ChIP-seq binding regions revealed significant consensus DNA binding motifs for Bcl11b. These data implicate Bcl11b as a novel regulator of the BDNF signaling pathway, which is disrupted in many neurological disorders. Specific targeting of the Bcl11b-DNA interaction could represent a novel therapeutic approach to lowering BDNF signaling specifically in striatal cells.

  5. Complex network inference from P300 signals: Decoding brain state under visual stimulus for able-bodied and disabled subjects

    Science.gov (United States)

    Gao, Zhong-Ke; Cai, Qing; Dong, Na; Zhang, Shan-Shan; Bo, Yun; Zhang, Jie

    2016-10-01

    Distinguishing brain cognitive behavior underlying disabled and able-bodied subjects constitutes a challenging problem of significant importance. Complex network has established itself as a powerful tool for exploring functional brain networks, which sheds light on the inner workings of the human brain. Most existing works in constructing brain network focus on phase-synchronization measures between regional neural activities. In contrast, we propose a novel approach for inferring functional networks from P300 event-related potentials by integrating time and frequency domain information extracted from each channel signal, which we show to be efficient in subsequent pattern recognition. In particular, we construct brain network by regarding each channel signal as a node and determining the edges in terms of correlation of the extracted feature vectors. A six-choice P300 paradigm with six different images is used in testing our new approach, involving one able-bodied subject and three disabled subjects suffering from multiple sclerosis, cerebral palsy, traumatic brain and spinal-cord injury, respectively. We then exploit global efficiency, local efficiency and small-world indices from the derived brain networks to assess the network topological structure associated with different target images. The findings suggest that our method allows identifying brain cognitive behaviors related to visual stimulus between able-bodied and disabled subjects.

  6. Signal features of surface electromyography in advanced Parkinson's disease during different settings of deep brain stimulation.

    Science.gov (United States)

    Rissanen, Saara M; Ruonala, Verneri; Pekkonen, Eero; Kankaanpää, Markku; Airaksinen, Olavi; Karjalainen, Pasi A

    2015-12-01

    Electromyography (EMG) and acceleration (ACC) measurements are potential methods for quantifying efficacy of deep brain stimulation (DBS) treatment in Parkinson's disease (PD). The treatment efficacy depends on the settings of DBS parameters (pulse amplitude, frequency and width). This study quantified, if EMG and ACC signal features differ between different DBS settings and if DBS effect is unequal between different muscles. EMGs were measured from biceps brachii (BB) and tibialis anterior (TA) muscles of 13 PD patients. ACCs were measured from wrists. Measurements were performed during seven different settings of DBS and analyzed using methods based on spectral analysis, signal morphology and nonlinear dynamics. The results showed significant within-subject differences in the EMG signal kurtosis, correlation dimension, recurrence rate and EMG-ACC coherence between different DBS settings for BB but not for TA muscles. Correlations between EMG feature values and clinical rest tremor and rigidity scores were weak but significant. Surface EMG features differed between different DBS settings and DBS effect was unequal between upper and lower limb muscles. EMG changes pointed to previously defined optimal settings in most of patients, which should be quantified even more deeply in the upcoming studies. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  7. mTOR and neuronal cell cycle reentry: How impaired brain insulin signaling promotes Alzheimer's disease.

    Science.gov (United States)

    Norambuena, Andrés; Wallrabe, Horst; McMahon, Lloyd; Silva, Antonia; Swanson, Eric; Khan, Shahzad S; Baerthlein, Daniel; Kodis, Erin; Oddo, Salvatore; Mandell, James W; Bloom, George S

    2017-02-01

    A major obstacle to presymptomatic diagnosis and disease-modifying therapy for Alzheimer's disease (AD) is inadequate understanding of molecular mechanisms of AD pathogenesis. For example, impaired brain insulin signaling is an AD hallmark, but whether and how it might contribute to the synaptic dysfunction and neuron death that underlie memory and cognitive impairment has been mysterious. Neuron death in AD is often caused by cell cycle reentry (CCR) mediated by amyloid-β oligomers (AβOs) and tau, the precursors of plaques and tangles. We now report that CCR results from AβO-induced activation of the protein kinase complex, mTORC1, at the plasma membrane and mTORC1-dependent tau phosphorylation, and that CCR can be prevented by insulin-stimulated activation of lysosomal mTORC1. AβOs were also shown previously to reduce neuronal insulin signaling. Our data therefore indicate that the decreased insulin signaling provoked by AβOs unleashes their toxic potential to cause neuronal CCR, and by extension, neuron death. Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  8. Selection of Optimal Frequency Bands of the Electroencephalogram Signal in Brain-Computer Interface

    Directory of Open Access Journals (Sweden)

    P. I. Sotnikov

    2015-01-01

    Full Text Available This article proposes a new method to increase the performance of brain-computer interface (BCI taking into account the individual characteristics of users. The idea of the method consists in the automatic selection of the most informative frequency bands of the electroencep halogram (EEG signal. As a measure of information content we use the accuracy of the imagery movement classes’ separation. The first part of the article explores differences in sensorimotor rhythms of the EEG signal between users. The second part provides a mathematical formulation of the optimal frequency bands selection problem, which is considered as a one-criterion optimization task. Boundaries of the frequency bands are considered as the variable parameters while the assessment of the classification accuracy acts as an objective function. In the following sections we propose to find a solution of the optimization task using a genetic algorithm. In the last section we compare the efficiency of the described method with other ones, including the algorithm based on the estimation of the EEG signal energy in the classical frequency bands. As a test data we use EEG recordings submitted to BCI Competition IV. In conclusion the main results and future lines of research are discussed.

  9. Candesartan and glycyrrhizin ameliorate ischemic brain damage through downregulation of the TLR signaling cascade.

    Science.gov (United States)

    Barakat, Waleed; Safwet, Nancy; El-Maraghy, Nabila N; Zakaria, Mohamed N M

    2014-02-05

    Stroke is the second leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. The final outcome of stroke is determined not only by the volume of the ischemic core, but also by the extent of secondary brain damage inflicted to penumbral tissues by brain swelling, impaired microcirculation, and inflammation. The only drug approved for the treatment ischemic stroke is recombinant tissue plasminogen activator (rt-PA). The current study was designed to investigate the protective effects of candesartan (0.15 mg/kg, orally) and glycyrrhizin (30 mg/kg, orally) experimentally-induced ischemic brain damage in C57BL/6 mice (middle cerebral artery occlusion, MCAO) in comparison to the effects of a standard neuroprotective drug (cerebrolysin, 7.5 mg/kg, IP). All drugs were administered 30 min before and 24h after MCAO. Both candesartan and glycyrrhizin ameliorated the deleterious effects of MCAO as indicated by the improvement in the performance of the animals in behaviour tests, reduction in brain infarction, neuronal degeneration, and leukocyte infiltration. In addition, MCAO induced a significant upregulation in the different elements of the TLR pathway including TLR-2 and TLR-4, Myd88, TRIF and IRF-3 and the downstream effectors TNF-α, IL-1β, IL-6 and NF-kB. All these changes were significantly ameliorated by treatment with candesartan and glycyrrhizin. The results of the current study represent a new indication for both candesartan and glycyrrhizin in the management of ischemic stroke with effects comparable to those of the standard neuroprotective drug cerebrolysin. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Activity-dependent, stress-responsive BDNF signaling and the quest for optimal brain health and resilience throughout the lifespan.

    Science.gov (United States)

    Rothman, S M; Mattson, M P

    2013-06-03

    During development of the nervous system, the formation of connections (synapses) between neurons is dependent upon electrical activity in those neurons, and neurotrophic factors produced by target cells play a pivotal role in such activity-dependent sculpting of the neural networks. A similar interplay between neurotransmitter and neurotrophic factor signaling pathways mediates adaptive responses of neural networks to environmental demands in adult mammals, with the excitatory neurotransmitter glutamate and brain-derived neurotrophic factor (BDNF) being particularly prominent regulators of synaptic plasticity throughout the central nervous system. Optimal brain health throughout the lifespan is promoted by intermittent challenges such as exercise, cognitive stimulation and dietary energy restriction, that subject neurons to activity-related metabolic stress. At the molecular level, such challenges to neurons result in the production of proteins involved in neurogenesis, learning and memory and neuronal survival; examples include proteins that regulate mitochondrial biogenesis, protein quality control, and resistance of cells to oxidative, metabolic and proteotoxic stress. BDNF signaling mediates up-regulation of several such proteins including the protein chaperone GRP-78, antioxidant enzymes, the cell survival protein Bcl-2, and the DNA repair enzyme APE1. Insufficient exposure to such challenges, genetic factors may conspire to impair BDNF production and/or signaling resulting in the vulnerability of the brain to injury and neurodegenerative disorders including Alzheimer's, Parkinson's and Huntington's diseases. Further, BDNF signaling is negatively regulated by glucocorticoids. Glucocorticoids impair synaptic plasticity in the brain by negatively regulating spine density, neurogenesis and long-term potentiation, effects that are potentially linked to glucocorticoid regulation of BDNF. Findings suggest that BDNF signaling in specific brain regions mediates some

  11. Nanocomposite polymeric electrolytes to record electrophysiological brain signals in prolonged, unconventional or extreme conditions.

    Science.gov (United States)

    Licoccia, Silvia; Luisa Di Vona, M; Romagnoli, Paola; Narici, Livio; Acquaviva, Massimo; Carozzo, Simone; Marco, Stefano Di; Saturno, Moreno; Sannita, Walter G; Traversa, Enrico

    2006-09-01

    Chemically stable nanocomposite iono-conducting polymeric membranes (based on lithium salts and nanocrystalline oxide powders dispersed in a polymethyl methacrylate matrix) performed successfully in the recording of human brain responses to visual stimulation. Impedance was higher than that of conventional electrodes. However, the electrophysiological signals recorded by acid Al(2)O(3) and neutral Al(2)O(3) 5 wt.% and 10 wt.% nanocomposite gel electrolytes were comparable to those obtained with standard electrodes, even without preliminary skin cleaning and in the absence of gel electrolytes allowing better contact with and skin-electrode ionic conductance. The electrochemical and mechanical characteristics of these membranes make them fit for human and animal research, for clinical application (specifically in emergencies, prolonged electrophysiological recordings), or in unconventional or extreme conditions when fluid electrolytes are unsuitable (e.g., biomedical space research).

  12. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Tansey Malú G

    2008-10-01

    Full Text Available Abstract The role of tumor necrosis factor (TNF as an immune mediator has long been appreciated but its function in the brain is still unclear. TNF receptor 1 (TNFR1 is expressed in most cell types, and can be activated by binding of either soluble TNF (solTNF or transmembrane TNF (tmTNF, with a preference for solTNF; whereas TNFR2 is expressed primarily by microglia and endothelial cells and is preferentially activated by tmTNF. Elevation of solTNF is a hallmark of acute and chronic neuroinflammation as well as a number of neurodegenerative conditions including ischemic stroke, Alzheimer's (AD, Parkinson's (PD, amyotrophic lateral sclerosis (ALS, and multiple sclerosis (MS. The presence of this potent inflammatory factor at sites of injury implicates it as a mediator of neuronal damage and disease pathogenesis, making TNF an attractive target for therapeutic development to treat acute and chronic neurodegenerative conditions. However, new and old observations from animal models and clinical trials reviewed here suggest solTNF and tmTNF exert different functions under normal and pathological conditions in the CNS. A potential role for TNF in synaptic scaling and hippocampal neurogenesis demonstrated by recent studies suggest additional in-depth mechanistic studies are warranted to delineate the distinct functions of the two TNF ligands in different parts of the brain prior to large-scale development of anti-TNF therapies in the CNS. If inactivation of TNF-dependent inflammation in the brain is warranted by additional pre-clinical studies, selective targeting of TNFR1-mediated signaling while sparing TNFR2 activation may lessen adverse effects of anti-TNF therapies in the CNS.

  13. Dysregulated brain immunity and neurotrophin signaling in Rett syndrome and autism spectrum disorders.

    Science.gov (United States)

    Theoharides, Theoharis C; Athanassiou, Marianna; Panagiotidou, Smaro; Doyle, Robert

    2015-02-15

    Rett syndrome is a neurodevelopmental disorder, which occurs in about 1:15,000 females and presents with neurologic and communication defects. It is transmitted as an X-linked dominant linked to mutations of the methyl-CpG-binding protein (MeCP2), a gene transcription suppressor, but its definitive pathogenesis is unknown thus hindering development of effective treatments. Almost half of children with Rett syndrome also have behavioral symptoms consistent with those of autism spectrum disorders (ASDs). PubMed was searched (2005-2014) using the terms: allergy, atopy, brain, brain-derived neurotrophic factor (BDNF), corticotropin-releasing hormone (CRH), cytokines, gene mutations, inflammation, mast cells (MCs), microglia, mitochondria, neurotensin (NT), neurotrophins, seizures, stress, and treatment. There are a number of intriguing differences and similarities between Rett syndrome and ASDs. Rett syndrome occurs in females, while ASDs more often in males, and the former has neurologic disabilities unlike ASDs. There is evidence of dysregulated immune system early in life in both conditions. Lack of microglial phagocytosis and decreased levels of BDNF appear to distinguish Rett syndrome from ASDs, in which there is instead microglia activation and/or proliferation and possibly defective BDNF signaling. Moreover, brain mast cell (MC) activation and focal inflammation may be more prominent in ASDs than Rett syndrome. The flavonoid luteolin blocks microglia and MC activation, provides BDNF-like activity, reverses Rett phenotype in mouse models, and has a significant benefit in children with ASDs. Appropriate formulations of luteolin or other natural molecules may be useful in the treatment of Rett syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. TLR4 signaling is involved in brain vascular toxicity of PCB153 bound to nanoparticles.

    Directory of Open Access Journals (Sweden)

    Bei Zhang

    Full Text Available PCBs bind to environmental particles; however, potential toxicity exhibited by such complexes is not well understood. The aim of the present study is to study the hypothesis that assembling onto nanoparticles can influence the PCB153-induced brain endothelial toxicity via interaction with the toll-like receptor 4 (TLR4. To address this hypothesis, TLR4-deficient and wild type control mice (males, 10 week old were exposed to PCB153 (5 ng/g body weight bound to chemically inert silica nanoparticles (PCB153-NPs, PCB153 alone, silica nanoparticles (NPs; diameter, 20 nm, or vehicle. Selected animals were also subjected to 40 min ischemia, followed by a 24 h reperfusion. As compared to exposure to PCB153 alone, treatment with PCB153-NP potentiated the brain infarct volume in control mice. Importantly, this effect was attenuated in TLR4-deficient mice. Similarly, PCB153-NP-induced proinflammatory responses and disruption of tight junction integrity were less pronounced in TLR4-deficient mice as compared to control animals. Additional in vitro experiments revealed that TLR4 mediates toxicity of PCB153-NP via recruitment of tumor necrosis factor-associated factor 6 (TRAF6. The results of current study indicate that binding to seemingly inert nanoparticles increase cerebrovascular toxicity of PCBs and suggest that targeting the TLR4/TRAF6 signaling may protect against these effects.

  15. TLR4 signaling is involved in brain vascular toxicity of PCB153 bound to nanoparticles.

    Science.gov (United States)

    Zhang, Bei; Choi, Jeong June; Eum, Sung Yong; Daunert, Sylvia; Toborek, Michal

    2013-01-01

    PCBs bind to environmental particles; however, potential toxicity exhibited by such complexes is not well understood. The aim of the present study is to study the hypothesis that assembling onto nanoparticles can influence the PCB153-induced brain endothelial toxicity via interaction with the toll-like receptor 4 (TLR4). To address this hypothesis, TLR4-deficient and wild type control mice (males, 10 week old) were exposed to PCB153 (5 ng/g body weight) bound to chemically inert silica nanoparticles (PCB153-NPs), PCB153 alone, silica nanoparticles (NPs; diameter, 20 nm), or vehicle. Selected animals were also subjected to 40 min ischemia, followed by a 24 h reperfusion. As compared to exposure to PCB153 alone, treatment with PCB153-NP potentiated the brain infarct volume in control mice. Importantly, this effect was attenuated in TLR4-deficient mice. Similarly, PCB153-NP-induced proinflammatory responses and disruption of tight junction integrity were less pronounced in TLR4-deficient mice as compared to control animals. Additional in vitro experiments revealed that TLR4 mediates toxicity of PCB153-NP via recruitment of tumor necrosis factor-associated factor 6 (TRAF6). The results of current study indicate that binding to seemingly inert nanoparticles increase cerebrovascular toxicity of PCBs and suggest that targeting the TLR4/TRAF6 signaling may protect against these effects.

  16. The representation of inflammatory signals in the brain – a model for subjective fatigue in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Katrin eHanken

    2014-12-01

    Full Text Available In multiple sclerosis (MS patients, fatigue is rated as one of the most common and disabling symptoms. However, the pathophysiology underlying this fatigue is not yet clear. Several lines of evidence suggest that immunological factors, such as elevated levels of proinflammatory cytokines, may contribute to subjective fatigue in MS patients. Proinflammatory cytokines represent primary mediators of immune-to-brain-communication, modulating changes in the neurophysiology of the central nervous system. Recently, we proposed a model arguing that fatigue in MS patients is a subjective feeling which is related to inflammation. Moreover, it implies that fatigue can be measured behaviorally only by applying specific cognitive tasks related to alertness and vigilance. In the present review we focus on the subjective feeling of MS-related fatigue. We examine the hypothesis that the subjective feeling of MS-related fatigue may be a variant of inflammation-induced sickness behavior, resulting from cytokine-mediated activity changes within brain areas involved in interoception and homeostasis including the insula, the anterior cingulate and the hypothalamus. We first present studies demonstrating a relationship between proinflammatory cytokines and subjective fatigue in healthy individuals, in people with inflammatory disorders, and particularly in MS patients. Subsequently, we discuss studies analyzing the impact of anti-inflammatory treatment on fatigue. In the next part of this review we present studies on the transmission and neural representation of inflammatory signals, with a special focus on possible neural concomitants of inflammation-induced fatigue. We also present two of our studies on the relationship between local gray and white matter atrophy and fatigue in MS patients. Finally, we discuss some implications of our findings and future perspectives.

  17. Leucine acts in the brain to suppress food intake but does not function as a physiological signal of low dietary protein

    Science.gov (United States)

    Laeger, Thomas; Reed, Scott D.; Henagan, Tara M.; Fernandez, Denise H.; Taghavi, Marzieh; Addington, Adele; Münzberg, Heike; Martin, Roy J.; Hutson, Susan M.

    2014-01-01

    Intracerebroventricular injections of leucine are sufficient to suppress food intake, but it remains unclear whether brain leucine signaling represents a physiological signal of protein balance. We tested whether variations in dietary and circulating levels of leucine, or all three branched-chain amino acids (BCAAs), contribute to the detection of reduced dietary protein. Of the essential amino acids (EAAs) tested, only intracerebroventricular injection of leucine (10 μg) was sufficient to suppress food intake. Isocaloric low- (9% protein energy; LP) or normal- (18% protein energy) protein diets induced a divergence in food intake, with an increased consumption of LP beginning on day 2 and persisting throughout the study (P dietary leucine or total BCAAs independently from total protein was neither necessary nor sufficient to induce hyperphagia, while chronic infusion of EAAs into the brain of LP rats failed to consistently block LP-induced hyperphagia. Collectively, these data suggest that circulating BCAAs are transiently reduced by dietary protein restriction, but variations in dietary or brain BCAAs alone do not explain the hyperphagia induced by a low-protein diet. PMID:24898843

  18. Fatty acid–induced gut-brain signaling attenuates neural and behavioral effects of sad emotion in humans

    OpenAIRE

    Van Oudenhove, Lukas; Mckie, Shane; Lassman, Daniel; Uddin, Bilal; Paine, Peter; Coen, Steven; Gregory, Lloyd; Tack, Jan; Aziz, Qasim

    2011-01-01

    Although a relationship between emotional state and feeding behavior is known to exist, the interactions between signaling initiated by stimuli in the gut and exteroceptively generated emotions remain incompletely understood. Here, we investigated the interaction between nutrient-induced gut-brain signaling and sad emotion induced by musical and visual cues at the behavioral and neural level in healthy nonobese subjects undergoing functional magnetic resonance imaging. Subjects received an in...

  19. Long-term music training tunes how the brain temporally binds signals from multiple senses.

    Science.gov (United States)

    Lee, Hweeling; Noppeney, Uta

    2011-12-20

    Practicing a musical instrument is a rich multisensory experience involving the integration of visual, auditory, and tactile inputs with motor responses. This combined psychophysics-fMRI study used the musician's brain to investigate how sensory-motor experience molds temporal binding of auditory and visual signals. Behaviorally, musicians exhibited a narrower temporal integration window than nonmusicians for music but not for speech. At the neural level, musicians showed increased audiovisual asynchrony responses and effective connectivity selectively for music in a superior temporal sulcus-premotor-cerebellar circuitry. Critically, the premotor asynchrony effects predicted musicians' perceptual sensitivity to audiovisual asynchrony. Our results suggest that piano practicing fine tunes an internal forward model mapping from action plans of piano playing onto visible finger movements and sounds. This internal forward model furnishes more precise estimates of the relative audiovisual timings and hence, stronger prediction error signals specifically for asynchronous music in a premotor-cerebellar circuitry. Our findings show intimate links between action production and audiovisual temporal binding in perception.

  20. Glioblastoma multiforme versus solitary supratentorial brain metastasis. Differentiation based on morphology and magnetic resonance signal characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Maurer, Martin H.; Wuestefeld, J.; Schaefer, M.L.; Wiener, E. [Charite - Universitaetsmedizin Berlin, Campus Virchow-Klinikum (Germany). Klinik fuer Diagnostische und Interventionelle Radiologie; Synowitz, M.; Lohkamp, L.N. [Charite - Universitaetsmedizin Berlin, Campus Virchow-Klinikum (Germany). Klinik fuer Neurochirurgie; Badakshi, H. [Charite - Universitaetsmedizin Berlin, Campus Virchow-Klinikum (Germany). Klinik fuer Strahlentherapie

    2013-03-15

    Purpose: To evaluate the diagnostic potential of a multi-factor analysis of morphometric parameters and magnetic resonance (MR) signal characteristics of a mass and peritumoral area to distinguish solitary supratentorial metastasis from glioblastoma multiforme (GBM). Materials and Methods: MR examinations of 51 patients with histologically proven GBM and 44 with a single supratentorial metastasis were evaluated. A large variety of morphologic criteria and MR signal characteristics in different sequences were analyzed. The data were subjected to logistic regression to investigate their ability to discriminate between GBM and cerebral metastasis. Receiver-operating characteristic (ROC) analysis was used to select an optimal cut-off point for prediction and to assess the predictive value in terms of sensitivity, specificity, and accuracy of the final model. Results: The logistic regression analysis revealed that the ratio of the maximum diameter of the peritumoral area measured on T2-weighted images (d T2) to the maximum diameter of the enhancing mass area (d T1, post-contrast) is the only useful criterion to distinguish single supratentorial brain metastasis from GBM with a lower ratio favoring GBM (accuracy 68 %, sensitivity 84 % and specificity 45 %). The cut-off point for the ratio d T2/d T1 post-contrast was calculated as 2.35. Conclusion: Measurement of maximum diameters of the peritumoral area in relation to the enhancing mass can be evaluated easily in the clinical routine to discriminate GBM from solitary supratentorial metastasis with an accuracy comparable to that of advanced MRI techniques. (orig.)

  1. β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain

    Directory of Open Access Journals (Sweden)

    Teppei Fujioka

    2017-02-01

    Full Text Available Cerebral ischemic stroke is a main cause of chronic disability. However, there is currently no effective treatment to promote recovery from stroke-induced neurological symptoms. Recent studies suggest that after stroke, immature neurons, referred to as neuroblasts, generated in a neurogenic niche, the ventricular-subventricular zone, migrate toward the injured area, where they differentiate into mature neurons. Interventions that increase the number of neuroblasts distributed at and around the lesion facilitate neuronal repair in rodent models for ischemic stroke, suggesting that promoting neuroblast migration in the post-stroke brain could improve efficient neuronal regeneration. To move toward the lesion, neuroblasts form chain-like aggregates and migrate along blood vessels, which are thought to increase their migration efficiency. However, the molecular mechanisms regulating these migration processes are largely unknown. Here we studied the role of β1-class integrins, transmembrane receptors for extracellular matrix proteins, in these migrating neuroblasts. We found that the neuroblast chain formation and blood vessel-guided migration critically depend on β1 integrin signaling. β1 integrin facilitated the adhesion of neuroblasts to laminin and the efficient translocation of their soma during migration. Moreover, artificial laminin-containing scaffolds promoted neuroblast chain formation and migration toward the injured area. These data suggest that laminin signaling via β1 integrin supports vasculature-guided neuronal migration to efficiently supply neuroblasts to injured areas. This study also highlights the importance of vascular scaffolds for cell migration in development and regeneration.

  2. Physiological and Pathological Roles of CaMKII-PP1 Signaling in the Brain

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    Norifumi Shioda

    2017-12-01

    Full Text Available Ca2+/calmodulin (CaM-dependent protein kinase II (CaMKII, a multifunctional serine (Ser/threonine (Thr protein kinase, regulates diverse activities related to Ca2+-mediated neuronal plasticity in the brain, including synaptic activity and gene expression. Among its regulators, protein phosphatase-1 (PP1, a Ser/Thr phosphatase, appears to be critical in controlling CaMKII-dependent neuronal signaling. In postsynaptic densities (PSDs, CaMKII is required for hippocampal long-term potentiation (LTP, a cellular process correlated with learning and memory. In response to Ca2+ elevation during hippocampal LTP induction, CaMKIIα, an isoform that translocates from the cytosol to PSDs, is activated through autophosphorylation at Thr286, generating autonomous kinase activity and a prolonged Ca2+/CaM-bound state. Moreover, PP1 inhibition enhances Thr286 autophosphorylation of CaMKIIα during LTP induction. By contrast, CaMKII nuclear import is regulated by Ser332 phosphorylation state. CaMKIIδ3, a nuclear isoform, is dephosphorylated at Ser332 by PP1, promoting its nuclear translocation, where it regulates transcription. In this review, we summarize physio-pathological roles of CaMKII/PP1 signaling in neurons. CaMKII and PP1 crosstalk and regulation of gene expression is important for neuronal plasticity as well as survival and/or differentiation.

  3. GRAPES—Grounding representations in action, perception, and emotion systems: How object properties and categories are represented in the human brain

    Science.gov (United States)

    Martin, Alex

    2016-01-01

    In this article, I discuss some of the latest functional neuroimaging findings on the organization of object concepts in the human brain. I argue that these data provide strong support for viewing concepts as the products of highly interactive neural circuits grounded in the action, perception, and emotion systems. The nodes of these circuits are defined by regions representing specific object properties (e.g., form, color, and motion) and thus are property-specific, rather than strictly modality-specific. How these circuits are modified by external and internal environmental demands, the distinction between representational content and format, and the grounding of abstract social concepts are also discussed. PMID:25968087

  4. GRAPES-Grounding representations in action, perception, and emotion systems: How object properties and categories are represented in the human brain.

    Science.gov (United States)

    Martin, Alex

    2016-08-01

    In this article, I discuss some of the latest functional neuroimaging findings on the organization of object concepts in the human brain. I argue that these data provide strong support for viewing concepts as the products of highly interactive neural circuits grounded in the action, perception, and emotion systems. The nodes of these circuits are defined by regions representing specific object properties (e.g., form, color, and motion) and thus are property-specific, rather than strictly modality-specific. How these circuits are modified by external and internal environmental demands, the distinction between representational content and format, and the grounding of abstract social concepts are also discussed.

  5. Increased brain size in mammals is associated with size variations in gene families with cell signalling, chemotaxis and immune-related functions.

    Science.gov (United States)

    Castillo-Morales, Atahualpa; Monzón-Sandoval, Jimena; Urrutia, Araxi O; Gutiérrez, Humberto

    2014-01-22

    Genomic determinants underlying increased encephalization across mammalian lineages are unknown. Whole genome comparisons have revealed large and frequent changes in the size of gene families, and it has been proposed that these variations could play a major role in shaping morphological and physiological differences among species. Using a genome-wide comparative approach, we examined changes in gene family size (GFS) and degree of encephalization in 39 fully sequenced mammalian species and found a significant over-representation of GFS variations in line with increased encephalization in mammals. We found that this relationship is not accounted for by known correlates of brain size such as maximum lifespan or body size and is not explained by phylogenetic relatedness. Genes involved in chemotaxis, immune regulation and cell signalling-related functions are significantly over-represented among those gene families most highly correlated with encephalization. Genes within these families are prominently expressed in the human brain, particularly the cortex, and organized in co-expression modules that display distinct temporal patterns of expression in the developing cortex. Our results suggest that changes in GFS associated with encephalization represent an evolutionary response to the specific functional requirements underlying increased brain size in mammals.

  6. Decomposition of Near-Infrared Spectroscopy Signals Using Oblique Subspace Projections: Applications in Brain Hemodynamic Monitoring.

    Science.gov (United States)

    Caicedo, Alexander; Varon, Carolina; Hunyadi, Borbala; Papademetriou, Maria; Tachtsidis, Ilias; Van Huffel, Sabine

    2016-01-01

    Clinical data is comprised by a large number of synchronously collected biomedical signals that are measured at different locations. Deciphering the interrelationships of these signals can yield important information about their dependence providing some useful clinical diagnostic data. For instance, by computing the coupling between Near-Infrared Spectroscopy signals (NIRS) and systemic variables the status of the hemodynamic regulation mechanisms can be assessed. In this paper we introduce an algorithm for the decomposition of NIRS signals into additive components. The algorithm, SIgnal DEcomposition base on Obliques Subspace Projections (SIDE-ObSP), assumes that the measured NIRS signal is a linear combination of the systemic measurements, following the linear regression model y = Ax + ϵ. SIDE-ObSP decomposes the output such that, each component in the decomposition represents the sole linear influence of one corresponding regressor variable. This decomposition scheme aims at providing a better understanding of the relation between NIRS and systemic variables, and to provide a framework for the clinical interpretation of regression algorithms, thereby, facilitating their introduction into clinical practice. SIDE-ObSP combines oblique subspace projections (ObSP) with the structure of a mean average system in order to define adequate signal subspaces. To guarantee smoothness in the estimated regression parameters, as observed in normal physiological processes, we impose a Tikhonov regularization using a matrix differential operator. We evaluate the performance of SIDE-ObSP by using a synthetic dataset, and present two case studies in the field of cerebral hemodynamics monitoring using NIRS. In addition, we compare the performance of this method with other system identification techniques. In the first case study data from 20 neonates during the first 3 days of life was used, here SIDE-ObSP decoupled the influence of changes in arterial oxygen saturation from the

  7. Metallic gold reduces TNFalpha expression, oxidative DNA damage and pro-apoptotic signals after experimental brain injury

    DEFF Research Database (Denmark)

    Pedersen, Mie Ostergaard; Larsen, Agnete; Pedersen, Dan Sonne

    2009-01-01

    -45 microm in size or the vehicle (placebo) were implanted in the cortical tissue followed by a cortical freeze-lesioning. At 1-2 weeks post-injury, brains were analyzed by using immunohistochemistry and markers of inflammation, oxidative stress and apoptosis. This study shows that gold treatment......Brain injury represents a major health problem and may result in chronic inflammation and neurodegeneration. Due to antiinflammatory effects of gold, we have investigated the cerebral effects of metallic gold particles following a focal brain injury (freeze-lesion) in mice. Gold particles 20...

  8. Dynamic neuronal ensembles: Issues in representing structure change in object-oriented, biologically-based brain models

    Energy Technology Data Exchange (ETDEWEB)

    Vahie, S.; Zeigler, B.P.; Cho, H. [Univ. of Arizona, Tucson, AZ (United States)

    1996-12-31

    This paper describes the structure of dynamic neuronal ensembles (DNEs). DNEs represent a new paradigm for learning, based on biological neural networks that use variable structures. We present a computational neural element that demonstrates biological neuron functionality such as neurotransmitter feedback absolute refractory period and multiple output potentials. More specifically, we will develop a network of neural elements that have the ability to dynamically strengthen, weaken, add and remove interconnections. We demonstrate that the DNE is capable of performing dynamic modifications to neuron connections and exhibiting biological neuron functionality. In addition to its applications for learning, DNEs provide an excellent environment for testing and analysis of biological neural systems. An example of habituation and hyper-sensitization in biological systems, using a neural circuit from a snail is presented and discussed. This paper provides an insight into the DNE paradigm using models developed and simulated in DEVS.

  9. Does visual working memory represent the predicted locations of future target objects? An event-related brain potential study.

    Science.gov (United States)

    Grubert, Anna; Eimer, Martin

    2015-11-11

    During the maintenance of task-relevant objects in visual working memory, the contralateral delay activity (CDA) is elicited over the hemisphere opposite to the visual field where these objects are presented. The presence of this lateralised CDA component demonstrates the existence of position-dependent object representations in working memory. We employed a change detection task to investigate whether the represented object locations in visual working memory are shifted in preparation for the known location of upcoming comparison stimuli. On each trial, bilateral memory displays were followed after a delay period by bilateral test displays. Participants had to encode and maintain three visual objects on one side of the memory display, and to judge whether they were identical or different to three objects in the test display. Task-relevant memory and test stimuli were located in the same visual hemifield in the no-shift task, and on opposite sides in the horizontal shift task. CDA components of similar size were triggered contralateral to the memorized objects in both tasks. The absence of a polarity reversal of the CDA in the horizontal shift task demonstrated that there was no preparatory shift of memorized object location towards the side of the upcoming comparison stimuli. These results suggest that visual working memory represents the locations of visual objects during encoding, and that the matching of memorized and test objects at different locations is based on a comparison process that can bridge spatial translations between these objects. This article is part of a Special Issue entitled SI: Prediction and Attention. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Neuro-developmental outcome at 18 months in premature infants with diffuse excessive high signal intensity on MR imaging of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Hart, Anthony [Sheffield Teaching Hospitals NHS Foundation Trust, Department of Neonatology, Sheffield (United Kingdom); University of Sheffield, Department of Academic Radiology, Sheffield, South Yorkshire (United Kingdom); Whitby, Elspeth; Paley, Martyn [University of Sheffield, Department of Academic Radiology, Sheffield, South Yorkshire (United Kingdom); Wilkinson, Stuart; Smith, Michael [Sheffield Teaching Hospitals NHS Foundation Trust, Department of Neonatology, Sheffield (United Kingdom); Alladi, Sathya [Sheffield Teaching Hospitals NHS Foundation Trust, Department of Child Development, Sheffield (United Kingdom)

    2011-10-15

    Diffuse excessive high signal intensity (DEHSI) may represent damage to the white matter in preterm infants, but may be best studied alongside quantitative markers. Limited published data exists on its neuro-developmental implications. The purpose of this study was to assess whether preterm children with DEHSI at term-corrected age have abnormal neuro-developmental outcome. This was a prospective observational study of 67 preterm infants with MRI of the brain around term-equivalent age, including diffusion-weighted imaging (DWI). Images were reported as being normal, overtly abnormal or to show DEHSI. A single observer placed six regions of interest in the periventricular white matter and calculated the apparent diffusion coefficients (ADC). DEHSI was defined as (1) high signal on T2-weighted images alone, (2) high signal with raised ADC values or (3) raised ADC values independent of visual appearances. The neuro-development was assessed around 18 months' corrected age using the Bayley Scales of Infant and Toddler Development (3rd Edition). Standard t tests compared outcome scores between imaging groups. No statistically significant difference in neuro-developmental outcome scores was seen between participants with normal MRI and DEHSI, regardless of which definition was used. Preterm children with DEHSI have similar neuro-developmental outcome to those with normal brain MRI, even if the definition includes objective markers alongside visual appearances. (orig.)

  11. Increases in Brain 1H-MR Glutamine and Glutamate Signals Following Acute Exhaustive Endurance Exercise in the Rat.

    Science.gov (United States)

    Świątkiewicz, Maciej; Fiedorowicz, Michał; Orzeł, Jarosław; Wełniak-Kamińska, Marlena; Bogorodzki, Piotr; Langfort, Józef; Grieb, Paweł

    2017-01-01

    Objective: Proton magnetic resonance spectroscopy (1H-MRS) in ultra-high magnetic field can be used for non-invasive quantitative assessment of brain glutamate (Glu) and glutamine (Gln) in vivo. Glu, the main excitatory neurotransmitter in the central nervous system, is efficiently recycled between synapses and presynaptic terminals through Glu-Gln cycle which involves glutamine synthase confined to astrocytes, and uses 60-80% of energy in the resting human and rat brain. During voluntary or involuntary exercise many brain areas are significantly activated, which certainly intensifies Glu-Gln cycle. However, studies on the effects of exercise on 1H-MRS Glu and/or Gln signals from the brain provided divergent results. The present study on rats was performed to determine changes in 1H-MRS signals from three brain regions engaged in motor activity consequential to forced acute exercise to exhaustion. Method: After habituation to treadmill running, rats were subjected to acute treadmill exercise continued to exhaustion. Each animal participating in the study was subject to two identical imaging sessions performed under light isoflurane anesthesia, prior to, and following the exercise bout. In control experiments, two imaging sessions separated by the period of rest instead of exercise were performed. 1H-NMR spectra were recorded from the cerebellum, striatum, and hippocampus using a 7T small animal MR scanner. Results: Following exhaustive exercise statistically significant increases in the Gln and Glx signals were found in all three locations, whereas increases in the Glu signal were found in the cerebellum and hippocampus. In control experiments, no changes in 1H-MRS signals were found. Conclusion: Increase in glutamine signals from the brain areas engaged in motor activity may reflect a disequilibrium caused by increased turnover in the glutamate-glutamine cycle and a delay in the return of glutamine from astrocytes to neurons. Increased turnover of Glu-Gln cycle

  12. Control of a two-dimensional movement signal by a noninvasive brain-computer interface in humans

    Science.gov (United States)

    Wolpaw, Jonathan R.; McFarland, Dennis J.

    2004-12-01

    Brain-computer interfaces (BCIs) can provide communication and control to people who are totally paralyzed. BCIs can use noninvasive or invasive methods for recording the brain signals that convey the user's commands. Whereas noninvasive BCIs are already in use for simple applications, it has been widely assumed that only invasive BCIs, which use electrodes implanted in the brain, can provide multidimensional movement control of a robotic arm or a neuroprosthesis. We now show that a noninvasive BCI that uses scalp-recorded electroencephalographic activity and an adaptive algorithm can provide humans, including people with spinal cord injuries, with multidimensional point-to-point movement control that falls within the range of that reported with invasive methods in monkeys. In movement time, precision, and accuracy, the results are comparable to those with invasive BCIs. The adaptive algorithm used in this noninvasive BCI identifies and focuses on the electroencephalographic features that the person is best able to control and encourages further improvement in that control. The results suggest that people with severe motor disabilities could use brain signals to operate a robotic arm or a neuroprosthesis without needing to have electrodes implanted in their brains. brain-machine interface | electroencephalography

  13. Maternal Inflammation Contributes to Brain Overgrowth and Autism-Associated Behaviors through Altered Redox Signaling in Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Janel E. Le Belle

    2014-11-01

    Full Text Available A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species.

  14. Exercise increases mTOR signaling in brain regions involved in cognition and emotional behavior.

    Science.gov (United States)

    Lloyd, Brian A; Hake, Holly S; Ishiwata, Takayuki; Farmer, Caroline E; Loetz, Esteban C; Fleshner, Monika; Bland, Sondra T; Greenwood, Benjamin N

    2017-04-14

    Exercise can enhance learning and memory and produce resistance against stress-related psychiatric disorders such as depression and anxiety. In rats, these beneficial effects of exercise occur regardless of exercise controllability: both voluntary and forced wheel running produce stress-protective effects. The mechanisms underlying these beneficial effects of exercise remain unknown. The mammalian target of rapamycin (mTOR) is a translation regulator important for cell growth, proliferation, and survival. mTOR has been implicated in enhancing learning and memory as well as antidepressant effects. Moreover, mTOR is sensitive to exercise signals such as metabolic factors. The effects of exercise on mTOR signaling, however, remain unknown. The goal of the present study was to test the hypothesis that exercise, regardless of controllability, increases levels of phosphorylated mTOR (p-mTOR) in brain regions important for learning and emotional behavior. Rats were exposed to 6 weeks of either sedentary (locked wheel), voluntary, or forced wheel running conditions. At 6 weeks, rats were sacrificed during peak running and levels of p-mTOR were measured using immunohistochemistry. Overall, both voluntary and forced exercise increased p-mTOR-positive neurons in the medial prefrontal cortex, striatum, hippocampus, hypothalamus, and amygdala compared to locked wheel controls. Exercise, regardless of controllability, also increased numbers of p-mTOR-positive glia in the striatum, hippocampus, and amygdala. For both neurons and glia, the largest increase in p-mTOR positive cells was observed after voluntary running, with forced exercise causing a more modest increase. Interestingly, voluntary exercise preferentially increased p-mTOR in astrocytes (GFAP+), while forced running increased p-mTOR in microglia (CD11+) in the inferior dentate gyrus. Results suggest that mTOR signaling is sensitive to exercise, but subtle differences exist depending on exercise controllability

  15. Effects of GSM and UMTS mobile telephony signals on neuron degeneration and blood-brain barrier permeation in the rat brain.

    Science.gov (United States)

    Poulletier de Gannes, Florence; Masuda, Hiroshi; Billaudel, Bernard; Poque-Haro, Emmanuelle; Hurtier, Annabelle; Lévêque, Philippe; Ruffié, Gilles; Taxile, Murielle; Veyret, Bernard; Lagroye, Isabelle

    2017-11-14

    Blood-brain barrier (BBB) permeation and neuron degeneration were assessed in the rat brain following exposure to mobile communication radiofrequency (RF) signals (GSM-1800 and UMTS-1950). Two protocols were used: (i) single 2 h exposure, with rats sacrificed immediately, and 1 h, 1, 7, or 50 days later, and (ii) repeated exposures (2 h/day, 5 days/week, for 4 weeks) with the effects assessed immediately and 50 days after the end of exposure. The rats' heads were exposed at brain-averaged specific absorption rates (BASAR) of 0.026, 0.26, 2.6, and 13 W/kg. No adverse impact in terms of BBB leakage or neuron degeneration was observed after single exposures or immediately after the end of repeated exposure, with the exception of a transient BBB leakage (UMTS, 0.26 W/kg). Fifty days after repeated exposure, the occurrence of degenerating neurons was unchanged on average. However, a significant increased albumin leakage was detected with both RF signals at 13 W/kg. In this work, the strongest, delayed effect was induced by GSM-1800 at 13 W/kg. Considering that 13 W/kg BASAR in the rat head is equivalent to 4 times as much in the human head, deleterious effects may occur following repeated human brain exposure above 50 W/kg.

  16. Prolonged maternal separation attenuates BDNF-ERK signaling correlated with spine formation in the hippocampus during early brain development.

    Science.gov (United States)

    Ohta, Ken-Ichi; Suzuki, Shingo; Warita, Katsuhiko; Kaji, Tomohiro; Kusaka, Takashi; Miki, Takanori

    2017-04-01

    Maternal separation (MS) is known to affect hippocampal function such as learning and memory, yet the molecular mechanism remains unknown. We hypothesized that these impairments are attributed to abnormities of neural circuit formation by MS, and focused on brain-derived neurotrophic factor (BDNF) as key factor because BDNF signaling has an essential role in synapse formation during early brain development. Using rat offspring exposed to MS for 6 h/day during postnatal days (PD) 2-20, we estimated BDNF signaling in the hippocampus during brain development. Our results show that MS attenuated BDNF expression and activation of extracellular signal-regulated kinase (ERK) around PD 7. Moreover, plasticity-related immediate early genes, which are transcriptionally regulated by BDNF-ERK signaling, were also reduced by MS around PD 7. Interestingly, detailed analysis revealed that MS particularly reduced expression of BDNF gene and immediate early genes in the cornu ammonis 1 (CA1) of hippocampus at PD 7. Considering that BDNF-ERK signaling is involved in spine formation, we next evaluated spine formation in the hippocampus during the weaning period. Our results show that MS particularly reduced mature spine density in proximal apical dendrites of CA1 pyramidal neurons at PD 21. These results suggest that MS could attenuate BDNF-ERK signaling during primary synaptogenesis with a region-specific manner, which is likely to lead to decreased spine formation and maturation observed in the hippocampal CA1 region. It is speculated that this incomplete spine formation during early brain development has an influence on learning capabilities throughout adulthood. © 2017 International Society for Neurochemistry.

  17. Impact of calcium signaling during infection of Neisseria meningitidis to human brain microvascular endothelial cells.

    Science.gov (United States)

    Asmat, Tauseef M; Tenenbaum, Tobias; Jonsson, Ann-Beth; Schwerk, Christian; Schroten, Horst

    2014-01-01

    The pili and outer membrane proteins of Neisseria meningitidis (meningococci) facilitate bacterial adhesion and invasion into host cells. In this context expression of meningococcal PilC1 protein has been reported to play a crucial role. Intracellular calcium mobilization has been implicated as an important signaling event during internalization of several bacterial pathogens. Here we employed time lapse calcium-imaging and demonstrated that PilC1 of meningococci triggered a significant increase in cytoplasmic calcium in human brain microvascular endothelial cells, whereas PilC1-deficient meningococci could not initiate this signaling process. The increase in cytosolic calcium in response to PilC1-expressing meningococci was due to efflux of calcium from host intracellular stores as demonstrated by using 2-APB, which inhibits the release of calcium from the endoplasmic reticulum. Moreover, pre-treatment of host cells with U73122 (phospholipase C inhibitor) abolished the cytosolic calcium increase caused by PilC1-expressing meningococci demonstrating that active phospholipase C (PLC) is required to induce calcium transients in host cells. Furthermore, the role of cytosolic calcium on meningococcal adherence and internalization was documented by gentamicin protection assay and double immunofluorescence (DIF) staining. Results indicated that chelation of intracellular calcium by using BAPTA-AM significantly impaired PilC1-mediated meningococcal adherence to and invasion into host endothelial cells. However, buffering of extracellular calcium by BAPTA or EGTA demonstrated no significant effect on meningococcal adherence to and invasion into host cells. Taken together, these results indicate that meningococci induce calcium release from intracellular stores of host endothelial cells via PilC1 and cytoplasmic calcium concentrations play a critical role during PilC1 mediated meningococcal adherence to and subsequent invasion into host endothelial cells.

  18. Impact of calcium signaling during infection of Neisseria meningitidis to human brain microvascular endothelial cells.

    Directory of Open Access Journals (Sweden)

    Tauseef M Asmat

    Full Text Available The pili and outer membrane proteins of Neisseria meningitidis (meningococci facilitate bacterial adhesion and invasion into host cells. In this context expression of meningococcal PilC1 protein has been reported to play a crucial role. Intracellular calcium mobilization has been implicated as an important signaling event during internalization of several bacterial pathogens. Here we employed time lapse calcium-imaging and demonstrated that PilC1 of meningococci triggered a significant increase in cytoplasmic calcium in human brain microvascular endothelial cells, whereas PilC1-deficient meningococci could not initiate this signaling process. The increase in cytosolic calcium in response to PilC1-expressing meningococci was due to efflux of calcium from host intracellular stores as demonstrated by using 2-APB, which inhibits the release of calcium from the endoplasmic reticulum. Moreover, pre-treatment of host cells with U73122 (phospholipase C inhibitor abolished the cytosolic calcium increase caused by PilC1-expressing meningococci demonstrating that active phospholipase C (PLC is required to induce calcium transients in host cells. Furthermore, the role of cytosolic calcium on meningococcal adherence and internalization was documented by gentamicin protection assay and double immunofluorescence (DIF staining. Results indicated that chelation of intracellular calcium by using BAPTA-AM significantly impaired PilC1-mediated meningococcal adherence to and invasion into host endothelial cells. However, buffering of extracellular calcium by BAPTA or EGTA demonstrated no significant effect on meningococcal adherence to and invasion into host cells. Taken together, these results indicate that meningococci induce calcium release from intracellular stores of host endothelial cells via PilC1 and cytoplasmic calcium concentrations play a critical role during PilC1 mediated meningococcal adherence to and subsequent invasion into host endothelial cells.

  19. Genome-wide association study signal at the 12q12 locus for Crohn's disease may represent associations with the MUC19 gene.

    Science.gov (United States)

    Kumar, Vijay; Mack, David R; Marcil, Valerie; Israel, David; Krupoves, Alfreda; Costea, Irina; Lambrette, Philippe; Grimard, Guy; Dong, Jinsong; Seidman, Ernest G; Amre, Devendra K; Levy, Emile

    2013-05-01

    Genome-wide association studies (GWAS) in Crohn's disease (CD) have identified associations with single-nucleotide polymorphism (SNP) rs11175593 at chromosome 12q12. The MUC19 and LRRK2 genes reside close to the GWAS signal, but it is as yet unclear which of the 2 genes represent the CD susceptibility genes. We studied associations between nonsynonymous coding variants in the MUC19 (5) and LRRK2 (3) genes in a case-control sample comprising CD cases aged associations were examined assuming different models of inheritance. A total of 530 cases and 600 controls were studied. The mean (±SD) age at diagnosis was 12.4 (±3.3). Most cases were male (57.4%). Most patients had ileocolonic disease location (48.8%) and inflammatory behavior at diagnosis (87.0%). Three MUC19 SNPs were nominally significantly associated with CD (rs11564245, Asp→His: P = 0.02; rs4768261, Ser→Phe: P = 0.0008; and rs2933353, Glu→Ala: P = 0.01). Associations with rs4768261 were maintained after corrections for multiple comparisons (permuted, P = 0.007). None of the LRRK2 SNPs were associated with CD. Haplotype analysis supported the single SNP associations noted with the MUC19 gene. GWAS signal at chromosome 12q12 for CD may represent associations with the MUC19 gene.

  20. Brain source localization: A new method based on MUltiple SIgnal Classification algorithm and spatial sparsity of the field signal for electroencephalogram measurements

    Science.gov (United States)

    Vergallo, P.; Lay-Ekuakille, A.

    2013-08-01

    Brain activity can be recorded by means of EEG (Electroencephalogram) electrodes placed on the scalp of the patient. The EEG reflects the activity of groups of neurons located in the head, and the fundamental problem in neurophysiology is the identification of the sources responsible of brain activity, especially if a seizure occurs and in this case it is important to identify it. The studies conducted in order to formalize the relationship between the electromagnetic activity in the head and the recording of the generated external field allow to know pattern of brain activity. The inverse problem, that is given the sampling field at different electrodes the underlying asset must be determined, is more difficult because the problem may not have a unique solution, or the search for the solution is made difficult by a low spatial resolution which may not allow to distinguish between activities involving sources close to each other. Thus, sources of interest may be obscured or not detected and known method in source localization problem as MUSIC (MUltiple SIgnal Classification) could fail. Many advanced source localization techniques achieve a best resolution by exploiting sparsity: if the number of sources is small as a result, the neural power vs. location is sparse. In this work a solution based on the spatial sparsity of the field signal is presented and analyzed to improve MUSIC method. For this purpose, it is necessary to set a priori information of the sparsity in the signal. The problem is formulated and solved using a regularization method as Tikhonov, which calculates a solution that is the better compromise between two cost functions to minimize, one related to the fitting of the data, and another concerning the maintenance of the sparsity of the signal. At the first, the method is tested on simulated EEG signals obtained by the solution of the forward problem. Relatively to the model considered for the head and brain sources, the result obtained allows to

  1. Trans-signaling is a dominant mechanism for the pathogenic actions of interleukin-6 in the brain.

    Science.gov (United States)

    Campbell, Iain L; Erta, Maria; Lim, Sue Ling; Frausto, Ricardo; May, Ulrike; Rose-John, Stefan; Scheller, Jürgen; Hidalgo, Juan

    2014-02-12

    IL-6 is implicated in the pathogenesis of various neuroinflammatory and neurodegenerative disorders of the CNS. IL-6 signals via binding to either the membrane bound IL-6Rα (classic signaling) or soluble (s)IL-6Ra (trans-signaling) that then form a complex with gp130 to activate the JAK/STAT signaling pathway. The importance of classic versus trans-signaling in mediating IL-6 actions in the living CNS is relatively unknown and was the focus of this investigation. Bigenic mice (termed GFAP-IL6/sgp130 mice) were generated with CNS-restricted, astrocyte-targeted production of IL-6 and coproduction of the specific inhibitor of IL-6 trans-signaling, human sgp130-Fc. Transgene-encoded IL-6 mRNA levels were similar in the brain of GFAP-IL6 and GFAP-IL6/sgp130 mice. However, GFAP-IL6/sgp130 mice had decreased pY(705)-STAT3 in the brain due to a reduction in the total number of pY(705)-STAT3-positive cells and a marked loss of pY(705)-STAT3 in specific cell types. Blockade of trans-signaling in the brain of the GFAP-IL6 mice significantly attenuated Serpina3n but not SOCS3 gene expression, whereas vascular changes including angiogenesis and blood-brain barrier leakage as well as gliosis were also reduced significantly. Hippocampal neurogenesis which was impaired in GFAP-IL6 mice was rescued in young GFAP-IL6 mice with cerebral sgp130 production. Finally, degenerative changes in the cerebellum characteristic of GFAP-IL6 mice were absent in GFAP-IL6/sgp130 mice. The findings indicate that in the CNS: (1) sgp130 is able to block IL-6 trans-signaling, (2) trans-signaling is important for IL-6 cellular communication with selective cellular and molecular targets, and (3) blocking of trans-signaling alleviates many of the detrimental effects of IL-6.

  2. Neuroprotective Effects of Physical Activity on the Brain A Closer Look at Trophic Factor Signaling

    Directory of Open Access Journals (Sweden)

    Cristy ePhillips

    2014-06-01

    Full Text Available While the relationship between increased physical activity and cognitive ability hasbeen conjectured for centuries, only recently have the mechanisms underlying this relationship began to emerge. Convergent evidence suggests that physical activity offers an affordable and effective method to improve cognitive function in all ages, particularly the elderly who are most vulnerable to neurodegenerative disorders. In addition to improving cardiac and immune function, physical activity alters trophic factor signaling and, in turn, neuronal function and structure in areas critical for cognition. Sustained exercise plays a role in modulating anti-inflammatory effects and may play a role in preserving cognitive function in aging and neuropathological conditions. Moreover, recent evidence suggests that myokines released by exercising muscles affect the expression of brain-derived neurotrophic factor synthesis in the dentate gyrus of the hippocampus, a finding that could lead to the identification of new and therapeutically important mediating factors. Given the growing numbers of individuals with cognitive impairment in the US population, a better understanding of how these factors work in aggregate to contribute to cognition is imperative, and constitutes an important first step toward developing non-pharmacological therapeutic strategies to improve cognition in vulnerable populations.

  3. A New Modular Brain Organization of the BOLD Signal during Natural Vision.

    Science.gov (United States)

    Kim, DoHyun; Kay, Kendrick; Shulman, Gordon L; Corbetta, Maurizio

    2017-07-13

    The resting blood oxygen level-dependent (BOLD) signal is synchronized in large-scale brain networks (resting-state networks, RSNs) defined by interregional temporal correlations (functional connectivity, FC). RSNs are thought to place strong constraints on task-evoked processing since they largely match the networks observed during task performance. However, this result may simply reflect the presence of spontaneous activity during both rest and task. Here, we examined the BOLD network structure of natural vision, as simulated by viewing of movies, using procedures that minimized the contribution of spontaneous activity. We found that the correlation between resting and movie-evoked FC (ρ = 0.60) was lower than previously reported. Hierarchical clustering and graph-theory analyses indicated a well-defined network structure during natural vision that differed from the resting structure, and emphasized functional groupings adaptive for natural vision. The visual network merged with a network for navigation, scene analysis, and scene memory. Conversely, the dorsal attention network was split and reintegrated into 2 groupings likely related to vision/scene and sound/action processing. Finally, higher order groupings from the clustering analysis combined internally directed and externally directed RSNs violating the large-scale distinction that governs resting-state organization. We conclude that the BOLD FC evoked by natural vision is only partly constrained by the resting network structure. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Decreased mTOR signalling reduces mitochondrial ROS in brain via accumulation of the telomerase protein TERT within mitochondria.

    Science.gov (United States)

    Miwa, Satomi; Czapiewski, Rafal; Wan, Tengfei; Bell, Amy; Hill, Kirsten N; von Zglinicki, Thomas; Saretzki, Gabriele

    2016-10-22

    Telomerase in its canonical function maintains telomeres in dividing cells. In addition, the telomerase protein TERT has non-telomeric functions such as shuttling to mitochondria resulting in a decreased oxidative stress, DNA damage and apoptosis. TERT protein persists in adult neurons and can co-localise to mitochondria under various stress conditions. We show here that TERT expression decreased in mouse brain during aging while release of reactive oxygen species (ROS) from the mitochondrial electron transport chain increased. Dietary restriction (DR) caused accumulation of TERT protein in mouse brain mitochondria correlating to decreased ROS release and improved learning and spatial short-term memory. Decreased mTOR signalling is a mediator of DR. Accordingly, feeding mice with rapamycin increased brain mitochondrial TERT and reduced ROS release. Importantly, the beneficial effects of rapamycin on mitochondrial function were absent in brains and fibroblasts from first generation TERT -/- mice, and when TERT shuttling was inhibited by the Src kinase inhibitor bosutinib. Taken together, our data suggests that the mTOR signalling pathway impinges on the mitochondrial localisation of TERT protein, which might in turn contribute to the protection of the brain by DR or rapamycin against age-associated mitochondrial ROS increase and cognitive decline.

  5. Optical mapping of the dominant frequency of brain signal oscillations in motor systems

    National Research Council Canada - National Science Library

    Feng-Mei Lu; Yi-Feng Wang; Juan Zhang; Hua-Fu Chen; Zhen Yuan

    2017-01-01

    Recent neuroimaging studies revealed that the dominant frequency of neural oscillations is brain-region-specific and can vary with frequency-specific reorganization of brain networks during cognition...

  6. A framework for using signal, noise, and variation to determine whether the brain controls movement synergies or single muscles.

    Science.gov (United States)

    Joshua, Mati; Lisberger, Stephen G

    2014-02-01

    We have used an analysis of signal and variation in motor behavior to elucidate the organization of the cerebellar and brain stem circuits that control smooth pursuit eye movements. We recorded from the abducens nucleus and identified floccular target neurons (FTNs) and other, non-FTN vestibular neurons. First, we assessed neuron-behavior correlations, defined as the trial-by-trial correlation between the variation in neural firing and eye movement, in brain stem neurons. In agreement with prior data from the cerebellum, neuron-behavior correlations during pursuit initiation were large in all neurons. Second, we asked whether movement variation arises upstream from, in parallel to, or downstream from a given site of recording. We developed a model that highlighted two measures: the ratio of the SDs of neural firing rate and eye movement ("SDratio") and the neuron-behavior correlation. The relationship between these measures defines possible sources of variation. During pursuit initiation, SDratio was approximately equal to neuron-behavior correlation, meaning that the source of signal and variation is upstream from the brain stem. During steady-state pursuit, neuron-behavior correlation became somewhat smaller than SDratio for FTNs, meaning that some variation may arise downstream in the brain stem. The data contradicted the model's predictions for sources of variation in pathways that run parallel to the site of recording. Because signal and noise are tightly linked in motor control, we take the source of variation as a proxy for the source of signal, leading us to conclude that the brain controls movement synergies rather than single muscles for eye movements.

  7. Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study.

    Directory of Open Access Journals (Sweden)

    Marina Yazigi Solis

    Full Text Available Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d(-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1 and on cognitive function before and after exercise in trained cyclists (Study 2.In Study 1, seven healthy vegetarians (3 women and 4 men and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation, with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task being performed before and after exercise on each occasion.In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99 or omnivores (p = 0.27; nor was there any effect when data from both groups were pooled (p = 0.19. Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27. In study 2, exercise improved cognitive function across all tests (P 0.05 of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise.28 d of beta-alanine supplementation at 6.4 g d(-1 appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists.

  8. Retardation of fetal dendritic development induced by gestational hyperglycemia is associated with brain insulin/IGF-I signals.

    Science.gov (United States)

    Jing, Yu-Hong; Song, Yan-Feng; Yao, Ya-Ming; Yin, Jie; Wang, De-Gui; Gao, Li-Ping

    2014-10-01

    Hyperglycemia is an essential risk factor for mothers and fetuses in gestational diabetes. Clinical observation has indicated that the offspring of mothers with diabetes shows impaired somatosensory function and IQ. However, only a few studies have explored the effects of hyperglycemia on fetal brain development. Neurodevelopment is susceptible to environmental conditions. Thus, this study aims to investigate the effects of maternal hyperglycemia on fetal brain development and to evaluate insulin and insulin-like growth factor-I (IGF-I) signals in fetal brain under hyperglycemia or controlled hyperglycemia. At day 1 of pregnancy, gestational rats were intraperitoneally injected with streptozocin (60 mg/kg). Some of the hyperglycemic gestational rats were injected with insulin (20 IU, two times a day) to control hyperglycemia; the others were injected with saline of equal volume. The gestational rats were sacrificed at days 14, 16, and 18 of embryo development. The dendritic spines of subplate cortex neurons in the fetal brain were detected by Golgi-Cox staining. The mRNA levels of insulin receptors (IRs) and IGF-IR in the fetal brain were measured using qRT-PCR. The protein levels of synaptophysin, IR, and IGF-IR in the fetal brain were detected by western blot. No significant difference in fetal brain formation was observed between the maternal hyperglycemic group and insulin-treated group. By contrast, obvious retardation of dendritic development in the fetus was observed in the maternal hyperglycemic group. Similarly, synaptophysin expression was lower in the fetus of the maternal hyperglycemic group than in that of the insulin-treated group. The mRNA and protein expression levels of IRs in the fetal brain were higher in the hyperglycemic group than in the insulin-treated group. By contrast, the levels of IGF-IR in the brain were lower in the fetus of the maternal hyperglycemic group than in that of the insulin-treated group. These results suggested that

  9. Blockade of Nociceptin Signaling Reduces Biochemical, Structural and Cognitive Deficits after Traumatic Brain Injury

    Science.gov (United States)

    2010-07-01

    euthanized and brains were excised. Brain-associated radioactivity was measured in a well γ- counter. The brains were then flash frozen in liquid ...electrophoretically transferred onto polyvinylidiene fluoride (PVDF) membranes. Membranes were blocked in 5% non-fat milk . Primary antibodies were incubated...cerebrovasodilation and hypoxia/ischemia following percussion fluid injury in piglets (Ross and Armstead, 2005

  10. Electrocommunication signals alone are sufficient to increase neurogenesis in the brain of adult electric fish, Apteronotus leptorhynchus.

    Science.gov (United States)

    Dunlap, Kent D; McCarthy, Elizabeth A; Jashari, Denisa

    2008-10-01

    Social interaction can have profound influences on the structure of the adult brain, but little is known about the precise stimulus feature found within social interaction that induces such brain plasticity. We examined the effects of social stimuli on cell addition and radial glial fiber formation in the brains of adult electric fish. These fish communicate primarily through weak, quasi-sinusoidal electric signals. Fish were housed in isolation, paired with another fish or exposed to only the electrocommunication signals of another fish for 7 days. After 3 days of exposure to these stimulus conditions, fish were injected with bromodeoxyuridine (BrdU) to mark newborn cells. We sacrificed the fish 4 days after BrdU injection and used immunohistochemistry to measure cell addition (BrdU+), the fraction of added cells that differentiated into neurons (BrdU+/NeuroTrace+) and the density of radial glia fibers (vimentin+) in the periventricular zone of the diencephalon. Fish that were exposed only to the electrocommunication signals of another fish and no other social stimuli had equivalent levels of cell addition and radial glial fiber density to fish that were housed with full social interaction and higher levels than fish housed in isolation. About 60% of the added cells differentiated into neurons; this fraction did not differ among treatment groups. Artificial sine wave electrical stimuli that mimicked electrocommunication signals were ineffective in increasing cell addition and glia fiber formation above those found in isolated fish. Thus, stimuli through a single modality are sufficient for inducing this brain plasticity, but the waveform or dynamic features of communication signals are crucial for the effect. (c) 2008 Wiley Periodicals, Inc.

  11. Analysis of brain signals with advanced signal processing techniques to help in the diagnosis of Alzheimer's disease.

    OpenAIRE

    Simons, Samantha M.

    2017-01-01

    Alzheimer’s disease (AD) is the most prevalent form of dementia in the world. Symptoms include progressive memory, cognitive and behavioural changes before death, caused by amyloid plaques and hyperphosphorated tau in the brain. The cause of AD is currently unknown and current interventions only slow the decline. Diagnosis is based on patient and familial history, interviews with close family and friends, cognitive, mental and physical tests. The electroencephalogram (EEG) records the ele...

  12. Multiple signaling pathways direct the initiation of tyrosine hydroxylase gene expression in cultured brain neurons.

    Science.gov (United States)

    Du, X; Iacovitti, L

    1997-10-15

    Previous studies have demonstrated that the synergistic interaction of acidic fibroblast growth factor (aFGF) and a second co-activator molecule can novelly induce expression of the CA biosynthetic enzyme tyrosine hydroxylase (TH) in non-TH expressing neurons of the striatum. Several co-activators have been identified, including substances present in L6 muscle cell extract (X. Du et al., J. Neurosci. 14 (1994) 7688-7694) catecholamines, such as dopamine (DA) (X. Du and L. Iacovitti, J. Neurosci. 15 (1995) 5420-5427; X. Du et al., Brain Res. 680 (1995) 229-233) and activators of protein kinase C (PKC) such as TPA (X. Du and L. Iacovitti, J. Neurochem. 68 (1997) 564-569). In the present study, we investigated whether activators of the protein kinase A (PKA) pathway also serve as effective co-activators of aFGF in the induction of TH gene expression. In addition, the combinatorial effects of the various TH-inducing agents were also evaluated. We found that, as with other co-activating molecules, the PKA stimulants IBMX and forskolin had no TH-inducing capacity when administered alone. However, co-treatment of 10 ng/ml aFGF with either (250 microM) IBMX or (10 microM) forskolin resulted in the novel expression of TH in 25% of plated neurons. The number of TH-expressing neurons was increased to 55% in aFGF-treated cultures co-incubated with aFGF and both (250 microM) IBMX and (10 microM) forskolin. Time course studies indicated that TH induction was rapid (peaking within 24 h) and enduring (lasting 4 days in culture). Induction of TH by aFGF and IBMX/forskolin was partially blocked by inhibitors of protein kinase, such as H7, H8 and H89, as well as pretreatment with protein (cyclohexamide) or RNA synthesis (amanitin and actinomycin D) inhibitors. The concomitant addition of combinations of co-activator molecules (DA, TPA and IBMX/forskolin) and aFGF resulted in the additive induction of TH. Maximal expression of TH (80% of striatal neurons) was accomplished when

  13. Conditional testing of multiple variants associated with bone mineral density in the FLNB gene region suggests that they represent a single association signal.

    Science.gov (United States)

    Mullin, Benjamin H; Mamotte, Cyril; Prince, Richard L; Spector, Tim D; Dudbridge, Frank; Wilson, Scott G

    2013-10-31

    Low bone mineral density (BMD) is a primary risk factor for osteoporosis and is a highly heritable trait, but appears to be influenced by many genes. Genome-wide linkage studies have highlighted the chromosomal region 3p14-p22 as a quantitative trait locus for BMD (LOD 1.1 - 3.5). The FLNB gene, which is thought to have a role in cytoskeletal actin dynamics, is located within this chromosomal region and presents as a strong candidate for BMD regulation. We have previously identified significant associations between four SNPs in the FLNB gene and BMD in women. We have also previously identified associations between five SNPs located 5' of the transcription start site (TSS) and in intron 1 of the FLNB gene and expression of FLNB mRNA in osteoblasts in vitro. The latter five SNPs were genotyped in this study to test for association with BMD parameters in a family-based population of 769 Caucasian women. Using FBAT, significant associations were seen for femoral neck BMD Z-score with the SNPs rs11720285, rs11130605 and rs9809315 (P = 0.004 - 0.043). These three SNPs were also found to be significantly associated with total hip BMD Z-score (P = 0.014 - 0.026). We then combined the genotype data for these three SNPs with the four SNPs we previously identified as associated with BMD and performed a conditional analysis to determine whether they represent multiple independent associations with BMD. The results from this analysis suggested that these variants represent a single association signal. The SNPs identified in our studies as associated with BMD appear to be part of a single association signal between the FLNB gene and BMD in our data. FLNB is one of several genes located in 3p14-p22 that has been identified as significantly associated with BMD in Caucasian women.

  14. Effect of naringenin on brain insulin signaling and cognitive functions in ICV-STZ induced dementia model of rats.

    Science.gov (United States)

    Yang, Wenqing; Ma, Jing; Liu, Zheng; Lu, Yongliang; Hu, Bin; Yu, Huarong

    2014-05-01

    Recent evidence indicates that severe abnormalities in brain glucose/energy metabolism and insulin signaling have been documented to take a pivotal role in early sporadic Alzheimer's disease pathology. It has been reported that naringenin (NAR), derived from citrus aurantium, exhibits antioxidant potential and protects the brain against neurodegeneration. The current study was designed to further investigate the protective effect of the NAR on neurodegeneration in a rat model of AD induced by an intracerebroventricular (ICV) injection of streptozotocin (STZ), and to determine whether this neuroprotective effect was associated with brain insulin signaling. Rats were injected bilaterally with ICV-STZ (3 mg/kg), while sham rats received the same volume of vehicle and then supplemented with NAR (25, 50 mg, 100 mg/kg, respectively) for 3 weeks. The ICV-STZ injected rats did not have elevated blood glucose levels. 21 days following ICV-STZ injection, rats treated with NAR had better learning and memory performance in the Morris water maze test compared with rats treated with saline. We demonstrated that NAR increased the mRNA expression of INS and INSR in cerebral cortex and hippocampus. In addition, NAR reversed ICV-STZ induced Tau hyper-phosphorylation in both hippocampus and cerebral cortex through downregulation of glycogen synthase kinase-3β (GSK-3β) activity, a key kinase in the insulin signaling. Brain levels of Abeta, which were elevated in ICV-STZ rats, were significantly reduced in NAR-treated rats via upregulation of insulin degrading enzyme. These effects were mediated by increased insulin and insulin receptors expression in the brain, suggesting that insulin sensitizer agents might have therapeutic efficacy in early AD.

  15. Effect of glucose and fructose on food intake via malonyl-CoA signaling in the brain.

    Science.gov (United States)

    Lane, M Daniel; Cha, Seung Hun

    2009-04-24

    In the brain malonyl-CoA serves the important function of monitoring and modulating energy balance. Because of its central role in the metabolism of higher animals, glucose acts as the principal indicator of global energy status. Specialized neuronal nuclei within the hypothalamus sense blood glucose and signal higher brain centers to adjust feeding behavior and energy expenditure accordingly. As the level of glucose entering the brain rises, food intake is suppressed. Energy status information triggered by glucose is transmitted via hypothalamic signaling intermediaries, i.e. AMPK and malonyl-CoA, to the orexigenic/anorexigenic neuropeptide system that determines hunger and energy expenditure. The central metabolism of glucose by the glycolytic pathway generates ATP which produces a compensatory decrease in AMP level and AMPK activity. Since acetyl-CoA carboxylase (ACC) is a substrate of AMPK, lowering AMP increases the catalytic activity of ACC and thereby, the level of its reaction product, malonyl-CoA. Malonyl-CoA signals the anorexigenic-orexigenic neuropeptide system to suppress food intake. Unlike glucose, however, centrally metabolized fructose increases food intake. This paradox results because fructose bypasses the rate-limiting step of glycolysis and uses a rapid ATP-requiring reaction that abruptly depletes ATP and provokes a compensatory rise in AMP. Thus, fructose has the opposite effect of glucose on the AMPK/malonyl-CoA signaling system and thereby, feeding behavior. The fact that fructose metabolism by the brain increases food intake and obesity risk raises health concerns in view of the large and increasing per capita consumption of high fructose sweeteners, especially by youth.

  16. Plasma from preeclamptic women increases blood-brain barrier permeability: role of vascular endothelial growth factor signaling.

    Science.gov (United States)

    Amburgey, Odül A; Chapman, Abbie C; May, Victor; Bernstein, Ira M; Cipolla, Marilyn J

    2010-11-01

    Circulating factors in preeclamptic women are thought to cause endothelial dysfunction and thereby contribute to the progression of this hypertensive condition. Despite the involvement of neurological complications in preeclampsia, there is a paucity of data regarding the effect of circulating factors on cerebrovascular function. Using a rat model of pregnancy, we investigated blood-brain barrier permeability, myogenic activity, and the influence of endothelial vasodilator mechanisms in cerebral vessels exposed intraluminally to plasma from normal pregnant or preeclamptic women. In addition, the role of vascular endothelial growth factor signaling in mediating changes in permeability in response to plasma was investigated. A 3-hour exposure to 20% normal pregnant or preeclamptic plasma increased blood-brain barrier permeability by ≈6.5- and 18.0-fold, respectively, compared with no plasma exposure (Pvascular endothelial growth factor receptor kinase activity prevented the increase in permeability in response to preeclamptic plasma but had no effect on changes in permeability of vessels exposed to normal pregnant plasma. Circulating factors in preeclamptic plasma did not affect myogenic activity or the influence of endothelium on vascular tone. These findings demonstrate that acute exposure to preeclamptic plasma has little effect on reactivity of cerebral arteries but significantly increases blood-brain barrier permeability. Prevention of increased permeability by inhibition of vascular endothelial growth factor signaling suggests that activation of this pathway may be responsible for increased blood-brain barrier permeability after exposure to preeclamptic plasma.

  17. Multi-Person Brain Activity Recognition via Comprehensive EEG Signal Analysis

    OpenAIRE

    Zhang, Xiang; Yao, Lina; Zhang, Dalin; Wang, Xianzhi; Sheng, Quan Z.; Gu, Tao

    2017-01-01

    An electroencephalography (EEG) based brain activity recognition is a fundamental field of study for a number of significant applications such as intention prediction, appliance control, and neurological disease diagnosis in smart home and smart healthcare domains. Existing techniques mostly focus on binary brain activity recognition for a single person, which limits their deployment in wider and complex practical scenarios. Therefore, multi-person and multi-class brain activity recognition h...

  18. Selecting Statistical Characteristics of Brain Signals to Detect Epileptic Seizures using Discrete Wavelet Transform and Perceptron Neural Network

    Directory of Open Access Journals (Sweden)

    Rezvan Abbasi

    2017-08-01

    Full Text Available Electroencephalogram signals (EEG have always been used in medical diagnosis. Evaluation of the statistical characteristics of EEG signals is actually the foundation of all brain signal processing methods. Since the correct prediction of disease status is of utmost importance, the goal is to use those models that have minimum error and maximum reliability. In anautomatic epileptic seizure detection system, we should be able to distinguish between EEG signals before, during and after seizure. Extracting useful characteristics from EEG data can greatly increase the classification accuracy. In this new approach, we first parse EEG signals to sub-bands in different categories with the help of discrete wavelet transform(DWT and then we derive statistical characteristics such as maximum, minimum, average and standard deviation for each sub-band. A multilayer perceptron (MLPneural network was used to assess the different scenarios of healthy and seizure among the collected signal sets. In order to assess the success and effectiveness of the proposed method, the confusion matrix was used and its accuracy was achieved98.33 percent. Due to the limitations and obstacles in analyzing EEG signals, the proposed method can greatly help professionals experimentally and visually in the classification and diagnosis of epileptic seizures.

  19. CXCL5 signaling is a shared pathway of neuroinflammation and blood-brain barrier injury contributing to white matter injury in the immature brain.

    Science.gov (United States)

    Wang, Lin-Yu; Tu, Yi-Fang; Lin, Yung-Chieh; Huang, Chao-Ching

    2016-01-06

    In very preterm infants, white matter injury is a prominent brain injury, and hypoxic ischemia (HI) and infection are the two primary pathogenic factors of this injury. Microglia and microvascular endothelial cells closely interact; therefore, a common signaling pathway may cause neuroinflammation and blood-brain barrier (BBB) damage after injury to the immature brain. CXC chemokine ligand 5 (CXCL5) is produced in inflammatory and endothelial cells by various organs in response to insults. CXCL5 levels markedly increased in the amniotic cavity in response to intrauterine infection and preterm birth in clinical studies. The objective of this study is to determine whether CXCL5 signaling is a shared pathway of neuroinflammation and BBB injury that contributes to white matter injury in the immature brain. Postpartum day 2 (P2) rat pups received lipopolysaccharide (LPS) followed by 90-min HI. Immunohistochemical analyses were performed to determine microglial activation, neutrophil infiltration, BBB damage, and myelin basic protein and glial fibrillary acidic protein expression. Immunofluorescence experiments were performed to determine the cellular distribution of CXCL5. Pharmacological tests were performed to inhibit or enhance CXCL5 activity. On P2, predominant increases in microglial activation and BBB damage were observed 24 h after LPS-sensitized HI induction, and white matter injury (decreased myelination and increased astrogliosis) was observed on P12 compared with controls. Immunohistochemical analyses revealed increased CXCL5 expression in the white matter 6 and 24 h after insult. Immunofluorescence experiments revealed upregulated CXCL5 expression in the activated microglia and endothelial cells 24 h after insult. CXCL5 inhibition by SB225002, a selective nonpeptide inhibitor of CXCR2, significantly attenuated microglial activation and BBB damage, increased myelination, and reduced astrogliosis in the white matter after LPS-sensitized HI. In addition, CXCL5

  20. Neurons in Vulnerable Regions of the Alzheimer's Disease Brain Display Reduced ATM Signaling.

    Science.gov (United States)

    Shen, Xuting; Chen, Jianmin; Li, Jiali; Kofler, Julia; Herrup, Karl

    2016-01-01

    Ataxia telangiectasia (A-T) is a multisystemic disease caused by mutations in the ATM (A-T mutated) gene. It strikes before 5 years of age and leads to dysfunctions in many tissues, including the CNS, where it leads to neurodegeneration, primarily in cerebellum. Alzheimer's disease (AD), by contrast, is a largely sporadic neurodegenerative disorder that rarely strikes before the 7th decade of life with primary neuronal losses in hippocampus, frontal cortex, and certain subcortical nuclei. Despite these differences, we present data supporting the hypothesis that a failure of ATM signaling is involved in the neuronal death in individuals with AD. In both, partially ATM-deficient mice and AD mouse models, neurons show evidence for a loss of ATM. In human AD, three independent indices of reduced ATM function-nuclear translocation of histone deacetylase 4, trimethylation of histone H3, and the presence of cell cycle activity-appear coordinately in neurons in regions where degeneration is prevalent. These same neurons also show reduced ATM protein levels. And though they represent only a fraction of the total neurons in each affected region, their numbers significantly correlate with disease stage. This previously unknown role for the ATM kinase in AD pathogenesis suggests that the failure of ATM function may be an important contributor to the death of neurons in AD individuals.

  1. Physical exercise mitigates doxorubicin-induced brain cortex and cerebellum mitochondrial alterations and cellular quality control signaling.

    Science.gov (United States)

    Marques-Aleixo, I; Santos-Alves, E; Balça, M M; Moreira, P I; Oliveira, P J; Magalhães, J; Ascensão, A

    2016-01-01

    Doxorubicin (DOX) is a highly effective anti-neoplastic agent, whose clinical use is limited by a dose-dependent mitochondrial toxicity in non-target tissues, including the brain. Here we analyzed the effects of distinct exercise modalities (12-week endurance treadmill-TM or voluntary free-wheel activity-FW) performed before and during sub-chronic DOX treatment on brain cortex and cerebellum mitochondrial bioenergetics, oxidative stress, permeability transition pore (mPTP), and proteins involved in mitochondrial biogenesis, apoptosis and auto(mito)phagy. Male Sprague-Dawley rats were divided into saline-sedentary (SAL+SED), DOX-sedentary (DOX+SED; 7-week DOX (2 mg · kg(-1)per week)), DOX+TM and DOX+FW. Animal behavior and post-sacrifice mitochondrial function were assessed. Oxidative phosphorylation (OXPHOS) subunits, oxidative stress markers or related proteins (SIRT3, p66shc, UCP2, carbonyls, MDA, -SH, aconitase, Mn-SOD), as well as proteins involved in mitochondrial biogenesis (PGC1α and TFAM) were evaluated. Apoptotic signaling was followed through caspases 3, 8 and 9-like activities, Bax, Bcl2, CypD, ANT and cofilin expression. Mitochondrial dynamics (Mfn1, Mfn2, OPA1 and DRP1) and auto(mito)phagy (LC3II, Beclin1, Pink1, Parkin and p62)-related proteins were measured by semi-quantitative Western blotting. DOX impaired behavioral performance, mitochondrial function, including lower resistance to mPTP and increased apoptotic signaling, decreased the content in OXPHOS complex subunits and increased oxidative stress in brain cortex and cerebellum. Molecular markers of mitochondrial biogenesis, dynamics and autophagy were also altered by DOX treatment in both brain subareas. Generally, TM and FW were able to mitigate DOX-related impairments in brain cortex and cerebellum mitochondrial activity, mPTP and apoptotic signaling. We conclude that the alterations in mitochondrial biogenesis, dynamics and autophagy markers induced by exercise performed before and during

  2. Polyphenols and the Human Brain: Plant “Secondary Metabolite” Ecologic Roles and Endogenous Signaling Functions Drive Benefits12

    Science.gov (United States)

    Kennedy, David O.

    2014-01-01

    Flavonoids and other polyphenols are ubiquitous plant chemicals that fulfill a range of ecologic roles for their home plant, including protection from a range of biotic and abiotic stressors and a pivotal role in the management of pathogenic and symbiotic soil bacteria and fungi. They form a natural part of the human diet, and evidence suggests that their consumption is associated with the beneficial modulation of a number of health-related variables, including those related to cardiovascular and brain function. Over recent years, the consensus as to the mechanisms responsible for these effects in humans has shifted away from polyphenols having direct antioxidant effects and toward their modulation of cellular signal transduction pathways. To date, little consideration has been given to the question of why, rather than how, these plant-derived chemicals might exert these effects. Therefore, this review summarizes the evidence suggesting that polyphenols beneficially affect human brain function and describes the current mechanistic hypotheses explaining these effects. It then goes on to describe the ecologic roles and potential endogenous signaling functions that these ubiquitous phytochemicals play within their home plant and discusses whether these functions drive their beneficial effects in humans via a process of “cross-kingdom” signaling predicated on the many conserved similarities in plant, microbial, and human cellular signal transduction pathways. PMID:25469384

  3. Polyphenols and the human brain: plant “secondary metabolite” ecologic roles and endogenous signaling functions drive benefits.

    Science.gov (United States)

    Kennedy, David O

    2014-09-01

    Flavonoids and other polyphenols are ubiquitous plant chemicals that fulfill a range of ecologic roles for their home plant, including protection from a range of biotic and abiotic stressors and a pivotal role in the management of pathogenic and symbiotic soil bacteria and fungi. They form a natural part of the human diet, and evidence suggests that their consumption is associated with the beneficial modulation of a number of health-related variables, including those related to cardiovascular and brain function. Over recent years, the consensus as to the mechanisms responsible for these effects in humans has shifted away from polyphenols having direct antioxidant effects and toward their modulation of cellular signal transduction pathways. To date, little consideration has been given to the question of why, rather than how, these plant-derived chemicals might exert these effects. Therefore, this review summarizes the evidence suggesting that polyphenols beneficially affect human brain function and describes the current mechanistic hypotheses explaining these effects. It then goes on to describe the ecologic roles and potential endogenous signaling functions that these ubiquitous phytochemicals play within their home plant and discusses whether these functions drive their beneficial effects in humans via a process of “cross-kingdom” signaling predicated on the many conserved similarities in plant, microbial, and human cellular signal transduction pathways.

  4. Using ipsilateral motor signals in the unaffected cerebral hemisphere as a signal platform for brain-computer interfaces in hemiplegic stroke survivors

    Science.gov (United States)

    Bundy, David T.; Wronkiewicz, Mark; Sharma, Mohit; Moran, Daniel W.; Corbetta, Maurizio; Leuthardt, Eric C.

    2012-06-01

    Brain-computer interface (BCI) systems have emerged as a method to restore function and enhance communication in motor impaired patients. To date, this has been applied primarily to patients who have a compromised motor outflow due to spinal cord dysfunction, but an intact and functioning cerebral cortex. The cortical physiology associated with movement of the contralateral limb has typically been the signal substrate that has been used as a control signal. While this is an ideal control platform in patients with an intact motor cortex, these signals are lost after a hemispheric stroke. Thus, a different control signal is needed that could provide control capability for a patient with a hemiparetic limb. Previous studies have shown that there is a distinct cortical physiology associated with ipsilateral, or same-sided, limb movements. Thus far, it was unknown whether stroke survivors could intentionally and effectively modulate this ipsilateral motor activity from their unaffected hemisphere. Therefore, this study seeks to evaluate whether stroke survivors could effectively utilize ipsilateral motor activity from their unaffected hemisphere to achieve this BCI control. To investigate this possibility, electroencephalographic (EEG) signals were recorded from four chronic hemispheric stroke patients as they performed (or attempted to perform) real and imagined hand tasks using either their affected or unaffected hand. Following performance of the screening task, the ability of patients to utilize a BCI system was investigated during on-line control of a one-dimensional control task. Significant ipsilateral motor signals (associated with movement intentions of the affected hand) in the unaffected hemisphere, which were found to be distinct from rest and contralateral signals, were identified and subsequently used for a simple online BCI control task. We demonstrate here for the first time that EEG signals from the unaffected hemisphere, associated with overt and

  5. Demonstration of brain noise on human EEG signals in perception of bistable images

    Science.gov (United States)

    Grubov, Vadim V.; Runnova, Anastasiya E.; Kurovskaya, Maria K.; Pavlov, Alexey N.; Koronovskii, Alexey A.; Hramov, Alexander E.

    2016-03-01

    In this report we studied human brain activity in the case of bistable visual perception. We proposed a new approach for quantitative characterization of this activity based on analysis of EEG oscillatory patterns and evoked potentials. Accordingly to theoretical background, obtained experimental EEG data and results of its analysis we studied a characteristics of brain activity during decision-making. Also we have shown that decisionmaking process has the special patterns on the EEG data.

  6. Clear signals or mixed messages: inter-individual emotion congruency modulates brain activity underlying affective body perception

    Science.gov (United States)

    de Gelder, B.

    2016-01-01

    The neural basis of emotion perception has mostly been investigated with single face or body stimuli. However, in daily life one may also encounter affective expressions by groups, e.g. an angry mob or an exhilarated concert crowd. In what way is brain activity modulated when several individuals express similar rather than different emotions? We investigated this question using an experimental design in which we presented two stimuli simultaneously, with same or different emotional expressions. We hypothesized that, in the case of two same-emotion stimuli, brain activity would be enhanced, while in the case of two different emotions, one emotion would interfere with the effect of the other. The results showed that the simultaneous perception of different affective body expressions leads to a deactivation of the amygdala and a reduction of cortical activity. It was revealed that the processing of fearful bodies, compared with different-emotion bodies, relied more strongly on saliency and action triggering regions in inferior parietal lobe and insula, while happy bodies drove the occipito-temporal cortex more strongly. We showed that this design could be used to uncover important differences between brain networks underlying fearful and happy emotions. The enhancement of brain activity for unambiguous affective signals expressed by several people simultaneously supports adaptive behaviour in critical situations. PMID:27025242

  7. Clear signals or mixed messages: inter-individual emotion congruency modulates brain activity underlying affective body perception.

    Science.gov (United States)

    de Borst, A W; de Gelder, B

    2016-08-01

    The neural basis of emotion perception has mostly been investigated with single face or body stimuli. However, in daily life one may also encounter affective expressions by groups, e.g. an angry mob or an exhilarated concert crowd. In what way is brain activity modulated when several individuals express similar rather than different emotions? We investigated this question using an experimental design in which we presented two stimuli simultaneously, with same or different emotional expressions. We hypothesized that, in the case of two same-emotion stimuli, brain activity would be enhanced, while in the case of two different emotions, one emotion would interfere with the effect of the other. The results showed that the simultaneous perception of different affective body expressions leads to a deactivation of the amygdala and a reduction of cortical activity. It was revealed that the processing of fearful bodies, compared with different-emotion bodies, relied more strongly on saliency and action triggering regions in inferior parietal lobe and insula, while happy bodies drove the occipito-temporal cortex more strongly. We showed that this design could be used to uncover important differences between brain networks underlying fearful and happy emotions. The enhancement of brain activity for unambiguous affective signals expressed by several people simultaneously supports adaptive behaviour in critical situations. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  8. EEG Recording and Online Signal Processing on Android: A Multiapp Framework for Brain-Computer Interfaces on Smartphone.

    Science.gov (United States)

    Blum, Sarah; Debener, Stefan; Emkes, Reiner; Volkening, Nils; Fudickar, Sebastian; Bleichner, Martin G

    2017-01-01

    Our aim was the development and validation of a modular signal processing and classification application enabling online electroencephalography (EEG) signal processing on off-the-shelf mobile Android devices. The software application SCALA (Signal ProCessing and CLassification on Android) supports a standardized communication interface to exchange information with external software and hardware. In order to implement a closed-loop brain-computer interface (BCI) on the smartphone, we used a multiapp framework, which integrates applications for stimulus presentation, data acquisition, data processing, classification, and delivery of feedback to the user. We have implemented the open source signal processing application SCALA. We present timing test results supporting sufficient temporal precision of audio events. We also validate SCALA with a well-established auditory selective attention paradigm and report above chance level classification results for all participants. Regarding the 24-channel EEG signal quality, evaluation results confirm typical sound onset auditory evoked potentials as well as cognitive event-related potentials that differentiate between correct and incorrect task performance feedback. We present a fully smartphone-operated, modular closed-loop BCI system that can be combined with different EEG amplifiers and can easily implement other paradigms.

  9. EEG Recording and Online Signal Processing on Android: A Multiapp Framework for Brain-Computer Interfaces on Smartphone

    Directory of Open Access Journals (Sweden)

    Sarah Blum

    2017-01-01

    Full Text Available Objective. Our aim was the development and validation of a modular signal processing and classification application enabling online electroencephalography (EEG signal processing on off-the-shelf mobile Android devices. The software application SCALA (Signal ProCessing and CLassification on Android supports a standardized communication interface to exchange information with external software and hardware. Approach. In order to implement a closed-loop brain-computer interface (BCI on the smartphone, we used a multiapp framework, which integrates applications for stimulus presentation, data acquisition, data processing, classification, and delivery of feedback to the user. Main Results. We have implemented the open source signal processing application SCALA. We present timing test results supporting sufficient temporal precision of audio events. We also validate SCALA with a well-established auditory selective attention paradigm and report above chance level classification results for all participants. Regarding the 24-channel EEG signal quality, evaluation results confirm typical sound onset auditory evoked potentials as well as cognitive event-related potentials that differentiate between correct and incorrect task performance feedback. Significance. We present a fully smartphone-operated, modular closed-loop BCI system that can be combined with different EEG amplifiers and can easily implement other paradigms.

  10. A New Pain Regulatory System via the Brain Long Chain Fatty Acid Receptor GPR40/FFA1 Signal.

    Science.gov (United States)

    Nakamoto, Kazuo

    2017-01-01

    An increasingly large number of pharmacological and physiological works on fatty acids have shown that the functional properties of fatty acids are regulated by the amount of individual fatty acid intake and the distribution of fatty acids among organs. Recently, it has been determined that G-protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFA1) is activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). GPR40/FFA1 is mainly expressed in the β cell of the pancreas, spinal cord and brain. It is reported that this receptor has a functional role in controlling blood glucose levels via the modulation of insulin secretion. However, its physiological function in the brain remains unknown. Our previous studies have shown that GPR40/FFA1 is expressed in pro-opiomelanocortin (POMC)-positive neurons of the arcuate nucleus, serotonergic neurons in the nucleus raphe magnus, and in noradrenergic neurons in the locus coeruleus. Furthermore, the intracerebroventricular injection of DHA or GW9508, which is a selective GPR40/FFA1 agonist, attenuates formalin-induced inflammatory pain behavior through increasing β-endorphin release in the hypothalamus. It also suppresses complete Freund's adjuvant-induced mechanical allodynia and thermal hyperalgesia. Our findings suggest that brain free long-chain fatty acids-GPR40/FFA1 signaling might have an important role in the modulation of endogenous pain control systems. In this review, I discuss the current status and our recent study regarding a new pain regulatory system via the brain long chain fatty acid receptor GPR40/FFA1 signal.

  11. Feasibility of the Application of Moment Of Inertia as a Feature to Study High-Frequency Bands in Brain Signals

    Directory of Open Access Journals (Sweden)

    Seyed Ali Shafiei

    2016-09-01

    Full Text Available Introduction Many features, emerging from mathematical techniques, have been used in the analysis of brain signals. In this study, the physical quantity of “moment of inertia” (MOI was introduced as a feature to enhance high-frequency waves (HFWs in electroencephalography (EEG. Materials and Methods In this research, the recorded EEGs from F3, F4, and Cz points in 20 males were used. A total of 30 noiseless epochs (4 sec with a 1 sec overlap were selected for each eyes-open and eyes-closed state from each brain signal. After averaging the relative power spectrum (RPS of 30 epochs and obtaining an RPS with low fluctuation, the MOIs of the power spectrum and each EEG band were calculated. Results The MOI enhanced the HFWs of brain signals; therefore, HFW fluctuations in the power spectrum of MOI were more evaluable and observable than those of RPS. Paired t-test showed no significant difference in the asymmetry of MOI between the eyes-open and eyes-closed states (P=0.227, while the MOIs of alpha and beta bands between these two states were significantly different [F(1, 38=11.8; P=0.001 and F(1, 38=12.9; P=0.001, respectively]. Conclusion This study demonstrated that the MOI of different frequency bands might be used as a feature for some patients who are different from healthy subjects in terms of high-frequency bands or performance of two hemispheres. Therefore, in order to ensure the applicability of the obtained results, evaluation of MOI for EEG of some disorders, such as attention-deficit hyperactivity disorder, alcoholism, and autism is suggested in future studies.

  12. 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.

  13. Simultaneous in vivo recording of local brain temperature and electrophysiological signals with a novel neural probe

    Science.gov (United States)

    Fekete, Z.; Csernai, M.; Kocsis, K.; Horváth, Á. C.; Pongrácz, A.; Barthó, P.

    2017-06-01

    Objective. Temperature is an important factor for neural function both in normal and pathological states, nevertheless, simultaneous monitoring of local brain temperature and neuronal activity has not yet been undertaken. Approach. In our work, we propose an implantable, calibrated multimodal biosensor that facilitates the complex investigation of thermal changes in both cortical and deep brain regions, which records multiunit activity of neuronal populations in mice. The fabricated neural probe contains four electrical recording sites and a platinum temperature sensor filament integrated on the same probe shaft within a distance of 30 µm from the closest recording site. The feasibility of the simultaneous functionality is presented in in vivo studies. The probe was tested in the thalamus of anesthetized mice while manipulating the core temperature of the animals. Main results. We obtained multiunit and local field recordings along with measurement of local brain temperature with accuracy of 0.14 °C. Brain temperature generally followed core body temperature, but also showed superimposed fluctuations corresponding to epochs of increased local neural activity. With the application of higher currents, we increased the local temperature by several degrees without observable tissue damage between 34-39 °C. Significance. The proposed multifunctional tool is envisioned to broaden our knowledge on the role of the thermal modulation of neuronal activity in both cortical and deeper brain regions.

  14. Reversible brain atrophy and subcortical high signal on MRI in a patient with anorexia nervosa

    Energy Technology Data Exchange (ETDEWEB)

    Drevelengas, A. [Asklipios-Aristotelio Diagnostic Centre, Thessaloniki (Greece); Dept. of Radiology, AHEPA University Hospital, Thessaloniki (Greece); Chourmouzi, D.; Boulogianni, G. [Asklipios-Aristotelio Diagnostic Centre, Thessaloniki (Greece); Pitsavas, G. [Paediatric Clinic, AHEPA University Hospital, Thessaloniki (Greece); Charitandi, A. [Dept. of Radiology, AHEPA University Hospital, Thessaloniki (Greece)

    2001-10-01

    Anorexia nervosa (AN), usually seen in young girls, is characterised by severe emaciation induced by self-imposed starvation. Enlargement of the ventricular system and sulci has been reported, as has high signal on T2-weighted images. We present a case with atrophic changes and high signal on T2-weighted images, which resolved completely following weight gain. (orig.)

  15. Effects of treadmill exercise on brain insulin signaling and ?-amyloid in intracerebroventricular streptozotocin induced-memory impairment in rats

    OpenAIRE

    Kang, Eun Bum; Cho, Joon Yong

    2014-01-01

    [Purpose] The purpose of the study is to explore effect of 6 weeks treadmill exercise on brain insulin signaling and ?-amyloid(A?). [Methods] The rat model of Alzheimer?s disease(AD) used in the present study was induced by the intracerebroventricular(ICV) streptozotocin(STZ). To produce the model of animal with AD, STZ(1.5mg/kg) was injected to a cerebral ventricle of both cerebrums of Sprague-Dawley rat(20 weeks). The experimental animals were divided into ICV-Sham(n=7), ICV-STZ CON(n=7), I...

  16. Deregulation of the Egfr/Ras Signaling Pathway Induces Age-related Brain Degeneration in the Drosophila Mutant vap

    Science.gov (United States)

    Botella, José A.; Kretzschmar, Doris; Kiermayer, Claudia; Feldmann, Pascale; Hughes, David A.; Schneuwly, Stephan

    2003-01-01

    Ras signaling has been shown to play an important role in promoting cell survival in many different tissues. Here we show that upregulation of Ras activity in adult Drosophila neurons induces neuronal cell death, as evident from the phenotype of vacuolar peduncle (vap) mutants defective in the Drosophila RasGAP gene, which encodes a Ras GTPase-activating protein. These mutants show age-related brain degeneration that is dependent on activation of the EGF receptor signaling pathway in adult neurons, leading to autophagic cell death (cell death type 2). These results provide the first evidence for a requirement of Egf receptor activity in differentiated adult Drosophila neurons and show that a delicate balance of Ras activity is essential for the survival of adult neurons. PMID:12529440

  17. Does Global Astrocytic Calcium Signaling Participate in Awake Brain State Transitions and Neuronal Circuit Function?

    DEFF Research Database (Denmark)

    Kjaerby, Celia; Rasmussen, Rune; Andersen, Mie

    2017-01-01

    We continuously need to adapt to changing conditions within our surrounding environment, and our brain needs to quickly shift between resting and working activity states in order to allow appropriate behaviors. These global state shifts are intimately linked to the brain-wide release...... look at the development and availability of innovative new methodological tools that are opening up for new ways of visualizing and perturbing astrocyte activity in awake behaving animals. With these new tools at hand, the field of astrocyte research will likely be able to elucidate the causal...... and mechanistic roles of astrocytes in complex behaviors within a very near future....

  18. Glutamate affects the production of epoxyeicosanoids within the brain: The up-regulation of brain CYP2J through the MAPK-CREB signaling pathway.

    Science.gov (United States)

    Liu, Mingzhou; Zhu, Quanfei; Wu, Jinhua; Yu, Xuming; Hu, Mingbai; Xie, Xianfei; Yang, Zheqiong; Yang, Jing; Feng, Yu-Qi; Yue, Jiang

    2017-04-15

    Glutamate is the major excitatory neurotransmitter in the brain, and chronic glutamate excitotoxicity has been thought to be involved in numerous neurodegenerative diseases. We investigated the effects of glutamate at concentrations lower than the usual extrasynaptic concentrations on the production of epoxyeicosanoids mediated by brain CYP2J. Glutamate increased CYP2J2 mRNA levels in astrocytes in a dose-dependent manner, while an antagonist of the metabotropic glutamate receptor subtype 5 (mGlu5 receptor) attenuated the glutamate-induced increases in CYP2J2 levels by glutamate. Glutamate increased the binding of cAMP response element-binding protein (CREB) with the CYP2J2 promoter, and the inhibition of the MAPK signaling pathway (ERK1/2, p38, and JNK) decreased the binding of CREB with the CYP2J2 promoter following the glutamate treatment. CREB activated the CYP2J2 promoter located at -1522 to -1317bp, and CREB overexpression significantly increased CYP2J2 mRNA levels. The CYP2J2 and mGlu5 mRNA levels were higher in the frontal cortex, hippocampus, cerebellum, and brainstem in adult rats that received a subcutaneous injection of monosodium l-glutamate at 1, 3, 5, and 7days of age. The data from the partial least-squares-discriminant analysis showed the epoxyeicosanoid profile of the hippocampus from the cerebellum, brain stem, and frontal cortex. The sum of the epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) was increased by 1.16-fold, 1.18-fold, and 1.19-fold in the frontal cortex, cerebellum, and brain stem, respectively, in rats treated with monosodium l-glutamate compared with the control group. The results suggest that brain CYP2J levels and CYP2J-mediated epoxyeicosanoid production can be regulated by extrasynaptic glutamate. The glutamate receptors expressed in astrocytes may mediate the regulation of drug-metabolizing enzymes and the metabolome of endogenous substances by glutamate. Copyright © 2017 Elsevier B.V. All rights

  19. Notch signaling and ageing.

    Science.gov (United States)

    Polychronidou, Eleftheria; Vlachakis, Dimitrios; Vlamos, Panayiotis; Baumann, Marc; Kossida, Sophia

    2015-01-01

    Notch signaling is a master controller of the neural stem cell and neural development maintaining a significant role in the normal brain function. Notch genes are involved in embryogenesis, nervous system, and cardiovascular and endocrine function. On the other side, there are studies representing the involvement of Notch mutations in sporadic Alzheimer disease, other neurodegenerative diseases such as Down syndrome, Pick's and Prion's disease, and CADASIL. This manuscript attempts to present a holistic view of the positive or negative contribution of Notch signaling in the adult brain, and at the same time to present and promote the promising research fields of study.

  20. Hypoxic preconditioning induces neuroprotective stanniocalcin-1 in brain via IL-6 signaling

    DEFF Research Database (Denmark)

    Westberg, Johan A; Serlachius, Martina; Lankila, Petri

    2007-01-01

    BACKGROUND AND PURPOSE: Exposure of animals for a few hours to moderate hypoxia confers relative protection against subsequent ischemic brain damage. This phenomenon, known as hypoxic preconditioning, depends on new RNA and protein synthesis, but its molecular mechanisms are poorly understood. In...

  1. Signal changes in gradient echo images of human brain induced by hypo- and hyperoxia

    DEFF Research Database (Denmark)

    Rostrup, Egill; Larsson, H B; Toft, P B

    1995-01-01

    The effect of hypoxia (inspired oxygen fraction, FiO2 of 10% and 16%) and hyperoxia (FiO2) of 100%) on gradient echo images of the brain using long echo times was investigated in six healthy volunteers (age 24-28 years). Different flip angles were used with an FiO2 of 10% to assess the importance...

  2. Perturbation and Nonlinear Dynamic Analysis of Acoustic Phonatory Signal in Parkinsonian Patients Receiving Deep Brain Stimulation

    Science.gov (United States)

    Lee, Victoria S.; Zhou, Xiao Ping; Rahn, Douglas A., III; Wang, Emily Q.; Jiang, Jack J.

    2008-01-01

    Nineteen PD patients who received deep brain stimulation (DBS), 10 non-surgical (control) PD patients, and 11 non-pathologic age- and gender-matched subjects performed sustained vowel phonations. The following acoustic measures were obtained on the sustained vowel phonations: correlation dimension (D[subscript 2]), percent jitter, percent shimmer,…

  3. MR Spectroscopy evaluation of white matter signal abnormalities of different non-neoplastic brain lesions

    Directory of Open Access Journals (Sweden)

    Randa O. Kaddah

    2016-03-01

    Conclusion: MRS is a noninvasive additional MRI technique to define the nature of non-neoplastic brain lesions. Together with image analysis, it may be the key to etiologic diagnosis or, at least, definition of the group where the lesion is classified, by detecting changes in different metabolites and peaks of inflammation.

  4. Evolution of the Brain Computing Interface (BCI and Proposed Electroencephalography (EEG Signals Based Authentication Model

    Directory of Open Access Journals (Sweden)

    Ramzan Qaseem

    2018-01-01

    Full Text Available With current advancements in the field of Brain Computer interface it is required to study how it will affect the other technologies currently in use. In this paper, the authors motivate the need of Brain Computing Interface in the era of IoT (Internet of Things, and analyze how BCI in the presence of IoT could have serious privacy breach if not protected by new kind of more secure protocols. Security breach and hacking has been around for a long time but now we are sensitive towards data as our lives depend on it. When everything is interconnected through IoT and considering that we control all interconnected things by means of our brain using BCI (Brain Computer Interface, the meaning of security breach becomes much more sensitive than in the past. This paper describes the old security methods being used for authentication and how they can be compromised. Considering the sensitivity of data in the era of IoT, a new form of authentication is required, which should incorporate BCI rather than usual authentication techniques.

  5. Estrogen activates rapid signaling in the brain: role of estrogen receptor alpha and estrogen receptor beta in neurons and glia.

    Science.gov (United States)

    Mhyre, A J; Dorsa, D M

    2006-01-01

    The aging process is known to coincide with a decline in circulating sex hormone levels in both men and women. Due to an increase in the average lifespan, a growing number of post-menopausal women are now receiving hormone therapy for extended periods of time. Recent findings of the Women's Health Initiative, however, have called into question the benefits of long-term hormone therapy for treating symptoms of menopause. The results of this study are still being evaluated, but it is clear that a better understanding of the molecular effects of estradiol is needed in order to develop new estrogenic compounds that activate specific mechanisms but lack adverse side effects. Traditionally, the effects of estradiol treatment have been ascribed to changes in gene expression, namely transcription at estrogen response elements. This review focuses on emerging information that estradiol can also activate a repertoire of membrane-initiated signaling pathways and that these rapid signaling events lead to functional changes at the cellular level. The various types of cells in the brain can respond differently to estradiol treatment based on the signaling properties of the cell, as well as which receptor, estrogen receptor alpha and/or estrogen receptor beta, is expressed. Taken together, these findings suggest that the estradiol-induced activation of membrane-initiated signaling pathways occurs in a cell-type specific manner and can differentially influence how the cells respond to various insults.

  6. Implications of the Primary Cilium in Cellular Signaling and Brain Development

    DEFF Research Database (Denmark)

    Lindbæk, Louise

    with signaling proteins, receptors, axonemal building blocks, and membrane. Collectively, these processes ensure the carefully regulated exit and entry of signaling mediators to/from the cilium, enabling the multitude of sensory functions of the organelle, including signaling through the Transforming Growth......Primary cilia are microtubule-based signaling organelles, emanating from the cell body on most cells in growth arrest. They comprise a highly conserved membrane structure, and coordinate a variety of cellular processes in development and homeostasis, including cell differentiation, migration, cell...... cycle regulation, and cell division. Defects in ciliary function is associated with a plethora of multi-systemic disorders affecting a variety of functions, including hearing, vision, kidneys, and liver. These are collectively termed ciliopathies. Maintenance and formation of the primary cilium...

  7. Non-contact time-domain imaging of functional brain activation and heterogeneity of superficial signals

    Science.gov (United States)

    Wabnitz, H.; Mazurenka, M.; Di Sieno, L.; Contini, D.; Dalla Mora, A.; Farina, A.; Hoshi, Y.; Kirilina, E.; Macdonald, R.; Pifferi, A.

    2017-07-01

    Non-contact scanning at small source-detector separation enables imaging of cerebral and extracranial signals at high spatial resolution and their separation based on early and late photons accounting for the related spatio-temporal characteristics.

  8. Statistical models for brain signals with properties that evolve across trials

    KAUST Repository

    Ombao, Hernando

    2017-12-07

    Most neuroscience cognitive experiments involve repeated presentations of various stimuli across several minutes or a few hours. It has been observed that brain responses, even to the same stimulus, evolve over the course of the experiment. These changes in brain activation and connectivity are believed to be associated with learning and/or habituation. In this paper, we present two general approaches to modeling dynamic brain connectivity using electroencephalograms (EEGs) recorded across replicated trials in an experiment. The first approach is the Markovian regime-switching vector autoregressive model (MS-VAR) which treats EEGs as realizations of an underlying brain process that switches between different states both within a trial and across trials in the entire experiment. The second is the slowly evolutionary locally stationary process (SEv-LSP) which characterizes the observed EEGs as a mixture of oscillatory activities at various frequency bands. The SEv-LSP model captures the dynamic nature of the amplitudes of the band-oscillations and cross-correlations between them. The MS-VAR model is able to capture abrupt changes in the dynamics while the SEv-LSP directly gives interpretable results. Moreover, it is nonparametric and hence does not suffer from model misspecification. For both of these models, time-evolving connectivity metrics in the frequency domain are derived from the model parameters for both functional and effective connectivity. We illustrate these two models for estimating cross-trial connectivity in selective attention using EEG data from an oddball paradigm auditory experiment where the goal is to characterize the evolution of brain responses to target stimuli and to standard tones presented randomly throughout the entire experiment. The results suggest dynamic changes in connectivity patterns over trials with inter-subject variability.

  9. Metastasis-associated kinase modulates Wnt signaling to regulate brain patterning and morphogenesis

    OpenAIRE

    Kibardin, Alexey; Ossipova, Olga; Sokol, Sergei Y.

    2006-01-01

    Wnt signaling is a major pathway regulating cell fate determination, cell proliferation and cell movements in vertebrate embryos. Distinct branches of this pathway activate β-catenin/TCF target genes and modulate morphogenetic movements in embryonic tissues by reorganizing the cytoskeleton. The selection of different molecular targets in the pathway is driven by multiple phosphorylation events. Here, we report that metastasis-associated kinase (MAK) is a novel regulator of Wnt signaling durin...

  10. Final Report on LDRD project 130784 : functional brain imaging by tunable multi-spectral Event-Related Optical Signal (EROS).

    Energy Technology Data Exchange (ETDEWEB)

    Speed, Ann Elizabeth; Spahn, Olga Blum; Hsu, Alan Yuan-Chun

    2009-09-01

    Functional brain imaging is of great interest for understanding correlations between specific cognitive processes and underlying neural activity. This understanding can provide the foundation for developing enhanced human-machine interfaces, decision aides, and enhanced cognition at the physiological level. The functional near infrared spectroscopy (fNIRS) based event-related optical signal (EROS) technique can provide direct, high-fidelity measures of temporal and spatial characteristics of neural networks underlying cognitive behavior. However, current EROS systems are hampered by poor signal-to-noise-ratio (SNR) and depth of measure, limiting areas of the brain and associated cognitive processes that can be investigated. We propose to investigate a flexible, tunable, multi-spectral fNIRS EROS system which will provide up to 10x greater SNR as well as improved spatial and temporal resolution through significant improvements in electronics, optoelectronics and optics, as well as contribute to the physiological foundation of higher-order cognitive processes and provide the technical foundation for miniaturized portable neuroimaging systems.

  11. Neuroprotective effect of breviscapine on traumatic brain injury in rats associated with the inhibition of GSK3β signaling pathway.

    Science.gov (United States)

    Jiang, Ling; Xia, Qing-Jie; Dong, Xiu-Juan; Hu, Yue; Chen, Zhi-Wei; Chen, Kang; Wang, Kun-Hua; Liu, Jia; Wang, Ting-Hua

    2017-04-01

    Breviscapine, a standardized Chinese herbal medicine extracted from Erigeron breviscapine, has been widely used to treat cerebrovascular diseases. However, there are no reports about the neuroprotective effects and underlying molecular mechanisms of breviscapine on traumatic brain injury (TBI). Therefore, this study was aimed to investigate the effects of breviscapine on rats with TBI insult and illuminate the underlying mechanism. We created a traumatic brain-injured model with breviscapine lateral ventricle injection and evaluated the expressional changes of glycogen synthase kinase 3 beta (GSK3β) as well as the GSK3β-involved signaling pathways including apoptosis and axonal growth. At 7, 14, 21days after injection, we found a great reduction of motor disability in TBI rats following breviscapine treatment, which was accompanied with a notably increased expression of phospho-Ser9-GSK3β (p-Ser9-GSK3β) and decreased expression of phosphor-Try216-GSK3β (p-Try216-GSK3β) at 7days after injection. Concomitantly, an enhanced expression of synaptic marker synaptophysin (SYP) together with a weakened expression of pro-apoptotic caspase3 was observed after TBI rats were treated with breviscapine. Terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling (TUNEL) immunohistochemical assay and SYP immunofluorescence staining also confirmed the result. This study suggests that breviscapine inhibits the GSK3β signaling pathway to promote neurobehavioral function following neurotrauma. These events may provide a new insight into the mechanism of breviscapine treating brain injury. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. A brain-computer interface for potential non-verbal facial communication based on EEG signals related to specific emotions.

    Science.gov (United States)

    Kashihara, Koji

    2014-01-01

    Unlike assistive technology for verbal communication, the brain-machine or brain-computer interface (BMI/BCI) has not been established as a non-verbal communication tool for amyotrophic lateral sclerosis (ALS) patients. Face-to-face communication enables access to rich emotional information, but individuals suffering from neurological disorders, such as ALS and autism, may not express their emotions or communicate their negative feelings. Although emotions may be inferred by looking at facial expressions, emotional prediction for neutral faces necessitates advanced judgment. The process that underlies brain neuronal responses to neutral faces and causes emotional changes remains unknown. To address this problem, therefore, this study attempted to decode conditioned emotional reactions to neutral face stimuli. This direction was motivated by the assumption that if electroencephalogram (EEG) signals can be used to detect patients' emotional responses to specific inexpressive faces, the results could be incorporated into the design and development of BMI/BCI-based non-verbal communication tools. To these ends, this study investigated how a neutral face associated with a negative emotion modulates rapid central responses in face processing and then identified cortical activities. The conditioned neutral face-triggered event-related potentials that originated from the posterior temporal lobe statistically significantly changed during late face processing (600-700 ms) after stimulus, rather than in early face processing activities, such as P1 and N170 responses. Source localization revealed that the conditioned neutral faces increased activity in the right fusiform gyrus (FG). This study also developed an efficient method for detecting implicit negative emotional responses to specific faces by using EEG signals. A classification method based on a support vector machine enables the easy classification of neutral faces that trigger specific individual emotions. In

  13. Tuning the brain for motherhood: prolactin-like central signalling in virgin, pregnant, and lactating female mice.

    Science.gov (United States)

    Salais-López, Hugo; Lanuza, Enrique; Agustín-Pavón, Carmen; Martínez-García, Fernando

    2017-03-01

    Prolactin is fundamental for the expression of maternal behaviour. In virgin female rats, prolactin administered upon steroid hormone priming accelerates the onset of maternal care. By contrast, the role of prolactin in mice maternal behaviour remains unclear. This study aims at characterizing central prolactin activity patterns in female mice and their variation through pregnancy and lactation. This was revealed by immunoreactivity of phosphorylated (active) signal transducer and activator of transcription 5 (pSTAT5-ir), a key molecule in the signalling cascade of prolactin receptors. We also evaluated non-hypophyseal lactogenic activity during pregnancy by administering bromocriptine, which suppresses hypophyseal prolactin release. Late-pregnant and lactating females showed significantly increased pSTAT5-ir resulting in a widespread pattern of immunostaining with minor variations between pregnant and lactating animals, which comprises nuclei of the sociosexual and maternal brain, including telencephalic (septum, nucleus of the stria terminalis, and amygdala), hypothalamic (preoptic, paraventricular, supraoptic, and ventromedial), and midbrain (periaqueductal grey) regions. During late pregnancy, this pattern was not affected by the administration of bromocriptine, suggesting it to be elicited mostly by non-hypophyseal lactogenic agents, likely placental lactogens. Virgin females displayed, instead, a variable pattern of pSTAT5-ir restricted to a subset of the brain nuclei labelled in pregnant and lactating mice. A hormonal substitution experiment confirmed that estradiol and progesterone contribute to the variability found in virgin females. Our results reflect how the shaping of the maternal brain takes place prior to parturition and suggest that lactogenic agents are important candidates in the development of maternal behaviours already during pregnancy.

  14. Another kind of 'BOLD Response': answering multiple-choice questions via online decoded single-trial brain signals.

    Science.gov (United States)

    Sorger, Bettina; Dahmen, Brigitte; Reithler, Joel; Gosseries, Olivia; Maudoux, Audrey; Laureys, Steven; Goebel, Rainer

    2009-01-01

    The term 'locked-in'syndrome (LIS) describes a medical condition in which persons concerned are severely paralyzed and at the same time fully conscious and awake. The resulting anarthria makes it impossible for these patients to naturally communicate, which results in diagnostic as well as serious practical and ethical problems. Therefore, developing alternative, muscle-independent communication means is of prime importance. Such communication means can be realized via brain-computer interfaces (BCIs) circumventing the muscular system by using brain signals associated with preserved cognitive, sensory, and emotional brain functions. Primarily, BCIs based on electrophysiological measures have been developed and applied with remarkable success. Recently, also blood flow-based neuroimaging methods, such as functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS), have been explored in this context. After reviewing recent literature on the development of especially hemodynamically based BCIs, we introduce a highly reliable and easy-to-apply communication procedure that enables untrained participants to motor-independently and relatively effortlessly answer multiple-choice questions based on intentionally generated single-trial fMRI signals that can be decoded online. Our technique takes advantage of the participants' capability to voluntarily influence certain spatio-temporal aspects of the blood oxygenation level-dependent (BOLD) signal: source location (by using different mental tasks), signal onset and offset. We show that healthy participants are capable of hemodynamically encoding at least four distinct information units on a single-trial level without extensive pretraining and with little effort. Moreover, real-time data analysis based on simple multi-filter correlations allows for automated answer decoding with a high accuracy (94.9%) demonstrating the robustness of the presented method. Following our 'proof of concept', the

  15. Power law scaling in synchronization of brain signals depends on cognitive load.

    Science.gov (United States)

    Tinker, Jesse; Velazquez, Jose Luis Perez

    2014-01-01

    As it has several features that optimize information processing, it has been proposed that criticality governs the dynamics of nervous system activity. Indications of such dynamics have been reported for a variety of in vitro and in vivo recordings, ranging from in vitro slice electrophysiology to human functional magnetic resonance imaging. However, there still remains considerable debate as to whether the brain actually operates close to criticality or in another governing state such as stochastic or oscillatory dynamics. A tool used to investigate the criticality of nervous system data is the inspection of power-law distributions. Although the findings are controversial, such power-law scaling has been found in different types of recordings. Here, we studied whether there is a power law scaling in the distribution of the phase synchronization derived from magnetoencephalographic recordings during executive function tasks performed by children with and without autism. Characterizing the brain dynamics that is different between autistic and non-autistic individuals is important in order to find differences that could either aid diagnosis or provide insights as to possible therapeutic interventions in autism. We report in this study that power law scaling in the distributions of a phase synchrony index is not very common and its frequency of occurrence is similar in the control and the autism group. In addition, power law scaling tends to diminish with increased cognitive load (difficulty or engagement in the task). There were indications of changes in the probability distribution functions for the phase synchrony that were associated with a transition from power law scaling to lack of power law (or vice versa), which suggests the presence of phenomenological bifurcations in brain dynamics associated with cognitive load. Hence, brain dynamics may fluctuate between criticality and other regimes depending upon context and behaviors.

  16. Power law scaling in synchronization of brain signals depends on cognitive load

    Directory of Open Access Journals (Sweden)

    Jose Luis ePerez Velazquez

    2014-05-01

    Full Text Available As it has several features that optimize information processing, it has been proposed that criticality governs the dynamics of nervous system activity. Indications of such dynamics have been reported for a variety of in vitro and in vivo recordings, ranging from in vitro slice electrophysiology to human functional magnetic resonance imaging. However, there still remains considerable debate as to whether the brain actually operates close to criticality or in another governing state such as stochastic or oscillatory dynamics. A tool used to investigate the criticality of nervous system data is the inspection of power-law distributions. Although the findings are controversial, such power-law scaling has been found in different types of recordings. Here, we studied whether there is a power law scaling in the distribution of the phase synchronization derived from magnetoencephalographic recordings during executive function tasks performed by children with and without autism. Characterizing the brain dynamics that is different between autistic and non-autistic individuals is important in order to find differences that could either aid diagnosis or provide insights as to possible therapeutic interventions in autism. We report in this study that power law scaling in the distributions of a phase synchrony index is not very common and its frequency of occurrence is similar in the control and the autism group. In addition, power law scaling tends to diminish with increased cognitive load (difficulty or engagement in the task. There were indications of changes in the probability distribution functions for the phase synchrony that were associated with a transition from power law scaling to lack of power law (or vice versa, which suggests the presence of phenomenological bifurcations in brain dynamics associated with cognitive load. Hence, brain dynamics may fluctuate between criticality and other regimes depending upon context and behaviours.

  17. From Intracerebral EEG Signals to Brain Connectivity: Identification of Epileptogenic Networks in Partial Epilepsy

    OpenAIRE

    Wendling, Fabrice; Chauvel, Patrick; Biraben, Arnaud; Bartolomei, Fabrice

    2010-01-01

    Epilepsy is a complex neurological disorder characterized by recurring seizures. In 30% of patients, seizures are insufficiently reduced by anti-epileptic drugs. In the case where seizures originate from a relatively circumscribed region of the brain, epilepsy is said to be partial and surgery can be indicated. The success of epilepsy surgery depends on the accurate localization and delineation of the epileptogenic zone (which often involves several structures), responsible for seizures. It r...

  18. Brain connectivity analysis from EEG signals using stable phase-synchronized states during face perception tasks

    Science.gov (United States)

    Jamal, Wasifa; Das, Saptarshi; Maharatna, Koushik; Pan, Indranil; Kuyucu, Doga

    2015-09-01

    Degree of phase synchronization between different Electroencephalogram (EEG) channels is known to be the manifestation of the underlying mechanism of information coupling between different brain regions. In this paper, we apply a continuous wavelet transform (CWT) based analysis technique on EEG data, captured during face perception tasks, to explore the temporal evolution of phase synchronization, from the onset of a stimulus. Our explorations show that there exists a small set (typically 3-5) of unique synchronized patterns or synchrostates, each of which are stable of the order of milliseconds. Particularly, in the beta (β) band, which has been reported to be associated with visual processing task, the number of such stable states has been found to be three consistently. During processing of the stimulus, the switching between these states occurs abruptly but the switching characteristic follows a well-behaved and repeatable sequence. This is observed in a single subject analysis as well as a multiple-subject group-analysis in adults during face perception. We also show that although these patterns remain topographically similar for the general category of face perception task, the sequence of their occurrence and their temporal stability varies markedly between different face perception scenarios (stimuli) indicating toward different dynamical characteristics for information processing, which is stimulus-specific in nature. Subsequently, we translated these stable states into brain complex networks and derived informative network measures for characterizing the degree of segregated processing and information integration in those synchrostates, leading to a new methodology for characterizing information processing in human brain. The proposed methodology of modeling the functional brain connectivity through the synchrostates may be viewed as a new way of quantitative characterization of the cognitive ability of the subject, stimuli and information integration

  19. Expression of the retinoic acid catabolic enzyme CYP26B1 in the human brain to maintain signaling homeostasis.

    Science.gov (United States)

    Stoney, Patrick N; Fragoso, Yara D; Saeed, Reem Bu; Ashton, Anna; Goodman, Timothy; Simons, Claire; Gomaa, Mohamed S; Sementilli, Angelo; Sementilli, Leonardo; Ross, Alexander W; Morgan, Peter J; McCaffery, Peter J

    2016-07-01

    Retinoic acid (RA) is a potent regulator of gene transcription via its activation of a set of nuclear receptors controlling transcriptional activation. Precise maintenance of where and when RA is generated is essential and achieved by local expression of synthetic and catabolic enzymes. The catabolic enzymes Cyp26a1 and Cyp26b1 have been studied in detail in the embryo, where they limit gradients of RA that form patterns of gene expression, crucial for morphogenesis. This paracrine role of RA has been assumed to occur in most tissues and that the RA synthetic enzymes release RA at a site distant from the catabolic enzymes. In contrast to the embryonic CNS, relatively little is known about RA metabolism in the adult brain. This study investigated the distribution of Cyp26a1 and Cyp26b1 transcripts in the rat brain, identifying several novel regions of expression, including the cerebral cortex for both enzymes and striatum for Cyp26b1. In vivo use of a new and potent inhibitor of the Cyp26 enzymes, ser 2-7, demonstrated a function for endogenous Cyp26 in the brain and that hippocampal RA levels can be raised by ser 2-7, altering the effect of RA on differential patterning of cell proliferation in the hippocampal region of neurogenesis, the subgranular zone. The expression of CYP26A1 and CYP26B1 was also investigated in the adult human brain and colocalization of CYP26A1 and the RA synthetic enzyme RALDH2 indicated a different, autocrine role for RA in human hippocampal neurons. Studies with the SH-SY5Y human neuroblastoma cell line implied that the co-expression of RA synthetic and catabolic enzymes maintains retinoid homeostasis within neurons. This presents a novel view of RA in human neurons as part of an autocrine, intracellular signaling system.

  20. The metabolic trinity, glucose-glycogen-lactate, links astrocytes and neurons in brain energetics, signaling, memory, and gene expression.

    Science.gov (United States)

    Dienel, Gerald A

    2017-01-10

    Glucose, glycogen, and lactate are traditionally identified with brain energetics, ATP turnover, and pathophysiology. However, recent studies extend their roles to include involvement in astrocytic signaling, memory consolidation, and gene expression. Emerging roles for these brain fuels and a readily-diffusible by-product are linked to differential fluxes in glycolytic and oxidative pathways, astrocytic glycogen dynamics, redox shifts, neuron-astrocyte interactions, and regulation of astrocytic activities by noradrenaline released from the locus coeruleus. Disproportionate utilization of carbohydrate compared with oxygen during brain activation is influenced by catecholamines, but its physiological basis is not understood and its magnitude may be affected by technical aspects of metabolite assays. Memory consolidation and gene expression are impaired by glycogenolysis blockade, and prevention of these deficits by injection of abnormally-high concentrations of lactate was interpreted as a requirement for astrocyte-to-neuron lactate shuttling in memory and gene expression. However, lactate transport was not measured and evidence for presumed shuttling is not compelling. In fact, high levels of lactate used to preserve memory consolidation and induce gene expression are sufficient to shut down neuronal firing via the HCAR1 receptor. In contrast, low lactate levels activate a receptor in locus coeruleus that stimulates noradrenaline release that may activate astrocytes throughout brain. Physiological relevance of exogenous concentrations of lactate used to mimic and evaluate metabolic, molecular, and behavioral effects of lactate requires close correspondence with the normal lactate levels, the biochemical and cellular sources and sinks, and specificity of lactate delivery to target cells. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. A Novel Brain Decoding Method: a Correlation Network Framework for Revealing Brain Connections

    OpenAIRE

    Yu, Siyu; Zheng, Nanning; Ma, Yongqiang; Wu, Hao; Chen, Badong

    2017-01-01

    Brain decoding is a hot spot in cognitive science, which focuses on reconstructing perceptual images from brain activities. Analyzing the correlations of collected data from human brain activities and representing activity patterns are two problems in brain decoding based on functional magnetic resonance imaging (fMRI) signals. However, existing correlation analysis methods mainly focus on the strength information of voxel, which reveals functional connectivity in the cerebral cortex. They te...

  2. Neuropilin-1 modulates interferon-γ-stimulated signaling in brain microvascular endothelial cells.

    Science.gov (United States)

    Wang, Ying; Cao, Ying; Mangalam, Ashutosh K; Guo, Yong; LaFrance-Corey, Reghann G; Gamez, Jeffrey D; Atanga, Pascal Aliihnui; Clarkson, Benjamin D; Zhang, Yuebo; Wang, Enfeng; Angom, Ramcharan Singh; Dutta, Kirthica; Ji, Baoan; Pirko, Istvan; Lucchinetti, Claudia F; Howe, Charles L; Mukhopadhyay, Debabrata

    2016-10-15

    Inflammatory response of blood-brain barrier (BBB) endothelial cells plays an important role in pathogenesis of many central nervous system inflammatory diseases, including multiple sclerosis; however, the molecular mechanism mediating BBB endothelial cell inflammatory response remains unclear. In this study, we first observed that knockdown of neuropilin-1 (NRP1), a co-receptor of several structurally diverse ligands, suppressed interferon-γ (IFNγ)-induced C-X-C motif chemokine 10 expression and activation of STAT1 in brain microvascular endothelial cells in a Rac1-dependent manner. Moreover, endothelial-specific NRP1-knockout mice, VECadherin-Cre-ERT2/NRP1flox/flox mice, showed attenuated disease progression during experimental autoimmune encephalomyelitis, a mouse neuroinflammatory disease model. Detailed analysis utilizing histological staining, quantitative PCR, flow cytometry and magnetic resonance imaging demonstrated that deletion of endothelial NRP1 suppressed neuron demyelination, altered lymphocyte infiltration, preserved BBB function and decreased activation of the STAT1-CXCL10 pathway. Furthermore, increased expression of NRP1 was observed in endothelial cells of acute multiple sclerosis lesions. Our data identify a new molecular mechanism of brain microvascular endothelial inflammatory response through NRP1-IFNγ crosstalk that could be a potential target for intervention of endothelial cell dysfunction in neuroinflammatory diseases. © 2016. Published by The Company of Biologists Ltd.

  3. Characterizing functional integrity: intraindividual brain signal variability predicts memory performance in patients with medial temporal lobe epilepsy.

    Science.gov (United States)

    Protzner, Andrea B; Kovacevic, Natasa; Cohn, Melanie; McAndrews, Mary Pat

    2013-06-05

    Computational modeling suggests that variability in brain signals provides important information regarding the system's capacity to adopt different network configurations that may promote optimal responding to stimuli. Although there is limited empirical work on this construct, a recent study indicates that age-related decreases in variability across the adult lifespan correlate with less efficient and less accurate performance. Here, we extend this construct to the assessment of cerebral integrity by comparing fMRI BOLD variability and fMRI BOLD amplitude in their ability to account for differences in functional capacity in patients with focal unilateral medial temporal dysfunction. We were specifically interested in whether either of these BOLD measures could identify a link between the affected medial temporal region and memory performance (as measured by a clinical test of verbal memory retention). Using partial least-squares analyses, we found that variability in a set of regions including the left hippocampus predicted verbal retention and, furthermore, this relationship was similar across a range of cognitive tasks measured during scanning (i.e., the same pattern was seen in fixation, autobiographical recall, and word generation). In contrast, signal amplitude in the hippocampus did not predict memory performance, even for a task that reliably activates the medial temporal lobes (i.e., autobiographical recall). These findings provide a powerful validation of the concept that variability in brain signals reflects functional integrity. Furthermore, this measure can be characterized as a robust biomarker in this clinical setting because it reveals the same pattern regardless of cognitive challenge or task engagement during scanning.

  4. Maternal obesity alters brain derived neurotrophic factor (BDNF) signaling in the placenta in a sexually dimorphic manner.

    Science.gov (United States)

    Prince, Calais S; Maloyan, Alina; Myatt, Leslie

    2017-01-01

    Obesity is a major clinical problem in obstetrics being associated with adverse pregnancy outcomes and fetal programming. Brain derived neurotrophic factor (BDNF), a validated miR-210 target, is necessary for placental development, fetal growth, glucose metabolism, and energy homeostasis. Plasma BDNF levels are reduced in obese individuals; however, placental BDNF has yet to be studied in the context of maternal obesity. In this study, we investigated the effect of maternal obesity and sexual dimorphism on placental BDNF signaling. BDNF signaling was measured in placentas from lean (pre-pregnancy BMI 30) women at term without medical complications that delivered via cesarean section without labor. MiRNA-210, BDNF mRNA, proBDNF, and mature BDNF were measured by RT - PCR, ELISA, and Western blot. Downstream signaling via TRKB (BDNF receptor) was measured using Western blot. Maternal obesity was associated with increased miRNA-210 and decreased BDNF mRNA in placentas from female fetuses, and decreased proBDNF in placentas from male fetuses. We also identified decreased mature BDNF in placentas from male fetuses when compared to female fetuses. Mir-210 expression was negatively correlated with mature BDNF protein. TRKB phosphorylated at tyrosine 817, not tyrosine 515, was increased in placentas from obese women. Maternal obesity was associated with increased phosphorylation of MAPK p38 in placentas from male fetuses, but not phosphorylation of ERK p42/44. BDNF regulation is complex and highly regulated. Pre-pregnancy/early maternal obesity adversely affects BDNF/TRKB signaling in the placenta in a sexually dimorphic manner. These data collectively suggest that induction of placental TRKB signaling could ameliorate the placental OB phenotype, thus improving perinatal outcome. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Dopamine D1-D2 receptor heteromer signaling pathway in the brain: emerging physiological relevance

    Directory of Open Access Journals (Sweden)

    Hasbi Ahmed

    2011-06-01

    Full Text Available Abstract Dopamine is an important catecholamine neurotransmitter modulating many physiological functions, and is linked to psychopathology of many diseases such as schizophrenia and drug addiction. Dopamine D1 and D2 receptors are the most abundant dopaminergic receptors in the striatum, and although a clear segregation between the pathways expressing these two receptors has been reported in certain subregions, the presence of D1-D2 receptor heteromers within a unique subset of neurons, forming a novel signaling transducing functional entity has been shown. Recently, significant progress has been made in elucidating the signaling pathways activated by the D1-D2 receptor heteromer and their potential physiological relevance.

  6. Dexamethasone Protects Neonatal Hypoxic-Ischemic Brain Injury via L-PGDS-Dependent PGD2-DP1-pERK Signaling Pathway

    Science.gov (United States)

    Gonzalez-Rodriguez, Pablo J.; Li, Yong; Martinez, Fabian; Zhang, Lubo

    2014-01-01

    Background and Purpose Glucocorticoids pretreatment confers protection against neonatal hypoxic-ischemic (HI) brain injury. However, the molecular mechanism remains poorly elucidated. We tested the hypothesis that glucocorticoids protect against HI brain injury in neonatal rat by stimulation of lipocalin-type prostaglandin D synthase (L-PGDS)-induced prostaglandin D2 (PGD2)-DP1-pERK mediated signaling pathway. Methods Dexamethasone and inhibitors were administered via intracerebroventricular (i.c.v) injections into 10-day-old rat brains. Levels of L-PGD2, D prostanoid (DP1) receptor, pERK1/2 and PGD2 were determined by Western immunoblotting and ELISA, respectively. Brain injury was evaluated 48 hours after conduction of HI in 10-day-old rat pups. Results Dexamethasone pretreatment significantly upregulated L-PGDS expression and the biosynthesis of PGD2. Dexamethasone also selectively increased isoform pERK-44 level in the neonatal rat brains. Inhibitors of L-PGDS (SeCl4), DP1 (MK-0524) and MAPK (PD98059) abrogated dexamethasone-induced increases in pERK-44 level, respectively. Of importance, these inhibitors also blocked dexamethasone-mediated neuroprotective effects against HI brain injury in neonatal rat brains. Conclusion Interaction of glucocorticoids-GR signaling and L-PGDS-PGD2-DP1-pERK mediated pathway underlies the neuroprotective effects of dexamethasone pretreatment in neonatal HI brain injury. PMID:25474649

  7. Neuroprotective effect of a novel gastrodin derivative against ischemic brain injury: involvement of peroxiredoxin and TLR4 signaling inhibition

    Science.gov (United States)

    Mao, Xiao-Na; Zhou, Hong-Jing; Yang, Xiao-Jia; Zhao, Li-Xue; Kuang, Xi; Chen, Chu; Liu, Dong-Ling; Du, Jun-Rong

    2017-01-01

    The inhibition of extracellular inflammatory peroxiredoxin (Prx) signaling appears to be a potential therapeutic strategy for neuroinflammatory injury after acute ischemic stroke. Gastrodin (Gas) is a phenolic glycoside that is used for the treatment of cerebral ischemia, accompanied by regulation of the autoimmune inflammatory response. The present study investigated the neuroprotective effects of Gas and its derivative, Gas-D, with a focus on the potential mechanism associated with inflammatory Prx–Toll-like receptor 4 (TLR4) signaling. Gas-D significantly inhibited Prx1-, Prx2-, and Prx4-induced inflammatory responses in RAW264.7 macrophages and H2O2-mediated oxidative injury in SH-SY5Y nerve cells. In rats, intraperitoneal Gas-D administration 10 h after reperfusion following 2-h middle cerebral artery occlusion (MCAO) ameliorated neurological deficits, brain infarction, and neuropathological alterations, including neuron loss, astrocyte and microglia/macrophage activation, T-lymphocyte invasion, and lipid peroxidation. Delayed Gas-D treatment significantly inhibited postischemic Prx1/2/4 expression and spillage, TLR4 signaling activation, and inflammatory mediator production. In contrast, Gas had no significant effects in either cell model or in MCAO rats under the same conditions. These results indicate that Gas-D may be a drug candidate with an extended therapeutic time window that blocks inflammatory responses and attenuates the expression and secretome of inflammatory Prxs in acute ischemic stroke. PMID:29207618

  8. Brain-derived neurotrophic factor signalling mediates the antidepressant-like effect of piperine in chronically stressed mice.

    Science.gov (United States)

    Mao, Qing-Qiu; Huang, Zhen; Zhong, Xiao-Ming; Xian, Yan-Fang; Ip, Siu-Po

    2014-03-15

    Previous studies in our laboratory have demonstrated that piperine produced antidepressant-like action in various mouse models of behavioral despair. This study aimed to investigate the role of brain-derived neurotrophic factor (BDNF) signalling in the antidepressant-like effect of piperine in mice exposed to chronic unpredictable mild stress (CUMS). The results showed that CUMS caused depression-like behavior in mice, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. It was also found that BDNF protein expression in the hippocampus and frontal cortex were significantly decreased in CUMS-treated mice. Chronic treatment of piperine at the dose of 10mg/kg significantly ameliorated behavioural deficits of CUMS-treated mice in the sucrose preference test and forced swim test. Piperine treatment also significantly decreased immobility time in the forced swim test in naive mice. In parallel, chronic piperine treatment significantly increased BDNF protein expression in the hippocampus and frontal cortex of both naive and CUMS-treated mice. In addition, inhibition of BDNF signalling by injection of K252a, an inhibitor of the BDNF receptor TrkB, significantly blocked the antidepressant-like effect of piperine in the sucrose preference test and forced swim test of CUMS-treated mice. Taken together, this study suggests that BDNF signalling is an essential mediator for the antidepressant-like effect of piperine. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Signal changes in gradient echo images of human brain induced by hypo- and hyperoxia

    DEFF Research Database (Denmark)

    Rostrup, Egill; Larsson, H B; Toft, P B

    1995-01-01

    of saturation effects. The total cerebral blood flow was measured by a phase mapping technique during normoxia as well as hypoxia (FiO2 of 10% and 16%) and hyperoxia (FiO2 of 50% and 100%). High relative signal changes were found, independently of the flip angle, with FiO2 of 10%. With a flip angle of 40...

  10. Traumatic brain injury dysregulates microRNAs to modulate cell signaling in rat hippocampus.

    Directory of Open Access Journals (Sweden)

    Liang Liu

    Full Text Available Traumatic brain injury (TBI is a common cause for cognitive and communication problems, but the molecular and cellular mechanisms are not well understood. Epigenetic modifications, such as microRNA (miRNA dysregulation, may underlie altered gene expression in the brain, especially hippocampus that plays a major role in spatial learning and memory and is vulnerable to TBI. To advance our understanding of miRNA in pathophysiological processes of TBI, we carried out a time-course microarray analysis of microRNA expression profile in rat ipsilateral hippocampus and examined histological changes, apoptosis and synapse ultrastructure of hippocampus post moderate TBI. We found that 10 out of 156 reliably detected miRNAs were significantly and consistently altered from one hour to seven days after injury. Bioinformatic and gene ontology analyses revealed 107 putative target genes, as well as several biological processes that might be initiated by those dysregulated miRNAs. Among those differentially expressed microRNAs, miR-144, miR-153 and miR-340-5p were confirmed to be elevated at all five time points after TBI by quantitative RT-PCR. Western blots showed three of the predicated target proteins, calcium/calmodulin-dependent serine protein kinase (CASK, nuclear factor erythroid 2-related factor 2 (NRF2 and alpha-synuclein (SNCA, were concurrently down- regulated, suggesting that miR-144, miR-153 and miR-340-5p may play important roles collaboratively in the pathogenesis of TBI-induced cognitive and memory impairments. These microRNAs might serve as potential targets for progress assessment and intervention against TBI to mitigate secondary damage to the brain.

  11. The fractionation of spoken language understanding by measuring electrical and magnetic brain signals.

    Science.gov (United States)

    Hagoort, Peter

    2008-03-12

    This paper focuses on what electrical and magnetic recordings of human brain activity reveal about spoken language understanding. Based on the high temporal resolution of these recordings, a fine-grained temporal profile of different aspects of spoken language comprehension can be obtained. Crucial aspects of speech comprehension are lexical access, selection and semantic integration. Results show that for words spoken in context, there is no 'magic moment' when lexical selection ends and semantic integration begins. Irrespective of whether words have early or late recognition points, semantic integration processing is initiated before words can be identified on the basis of the acoustic information alone. Moreover, for one particular event-related brain potential (ERP) component (the N400), equivalent impact of sentence- and discourse-semantic contexts is observed. This indicates that in comprehension, a spoken word is immediately evaluated relative to the widest interpretive domain available. In addition, this happens very quickly. Findings are discussed that show that often an unfolding word can be mapped onto discourse-level representations well before the end of the word. Overall, the time course of the ERP effects is compatible with the view that the different information types (lexical, syntactic, phonological, pragmatic) are processed in parallel and influence the interpretation process incrementally, that is as soon as the relevant pieces of information are available. This is referred to as the immediacy principle.

  12. mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis.

    Science.gov (United States)

    Foerster, Philippe; Daclin, Marie; Asm, Shihavuddin; Faucourt, Marion; Boletta, Alessandra; Genovesio, Auguste; Spassky, Nathalie

    2017-01-15

    Radial glial cells (RCGs) are self-renewing progenitor cells that give rise to neurons and glia during embryonic development. Throughout neurogenesis, these cells contact the cerebral ventricles and bear a primary cilium. Although the role of the primary cilium in embryonic patterning has been studied, its role in brain ventricular morphogenesis is poorly characterized. Using conditional mutants, we show that the primary cilia of radial glia determine the size of the surface of their ventricular apical domain through regulation of the mTORC1 pathway. In cilium-less mutants, the orientation of the mitotic spindle in radial glia is also significantly perturbed and associated with an increased number of basal progenitors. The enlarged apical domain of RGCs leads to dilatation of the brain ventricles during late embryonic stages (ventriculomegaly), which initiates hydrocephalus during postnatal stages. These phenotypes can all be significantly rescued by treatment with the mTORC1 inhibitor rapamycin. These results suggest that primary cilia regulate ventricle morphogenesis by acting as a brake on the mTORC1 pathway. This opens new avenues for the diagnosis and treatment of hydrocephalus. © 2017. Published by The Company of Biologists Ltd.

  13. Region-specific RNA m6A methylation represents a new layer of control in the gene regulatory network in the mouse brain.

    Science.gov (United States)

    Chang, Mengqi; Lv, Hongyi; Zhang, Weilong; Ma, Chunhui; He, Xue; Zhao, Shunli; Zhang, Zhi-Wei; Zeng, Yi-Xin; Song, Shuhui; Niu, Yamei; Tong, Wei-Min

    2017-09-01

    N6-methyladenosine (m6A) is the most abundant epitranscriptomic mark found on mRNA and has important roles in various physiological processes. Despite the relatively high m6A levels in the brain, its potential functions in the brain remain largely unexplored. We performed a transcriptome-wide methylation analysis using the mouse brain to depict its region-specific methylation profile. RNA methylation levels in mouse cerebellum are generally higher than those in the cerebral cortex. Heterogeneity of RNA methylation exists across different brain regions and different types of neural cells including the mRNAs to be methylated, their methylation levels and methylation site selection. Common and region-specific methylation have different preferences for methylation site selection and thereby different impacts on their biological functions. In addition, high methylation levels of fragile X mental retardation protein (FMRP) target mRNAs suggest that m6A methylation is likely to be used for selective recognition of target mRNAs by FMRP in the synapse. Overall, we provide a region-specific map of RNA m6A methylation and characterize the distinct features of specific and common methylation in mouse cerebellum and cerebral cortex. Our results imply that RNA m6A methylation is a newly identified element in the region-specific gene regulatory network in the mouse brain. © 2017 The Authors.

  14. Human brain dynamics: the analysis of EEG signals with Tsallis information measure

    Science.gov (United States)

    Capurro, A.; Diambra, L.; Lorenzo, D.; Macadar, O.; Martin, M. T.; Mostaccio, C.; Plastino, A.; Pérez, J.; Rofman, E.; Torres, M. E.; Velluti, J.

    We undertake the study of human EEG-signals by recourse to a wavelet based multiresolution analysis as adapted to an Information-Measure-Scenario. Different information measures are employed. It is shown that non-extensive ones seem to be of particular usefulness. Their use opens up perspectives of building up automatic detection devices. Conjectures concerning general characteristics of focal epilepsy are formulated on the basis of a Tsallis-type of analysis.

  15. Mathematical approach to recover EEG brain signals with artifacts by means of Gram-Schmidt transform

    Science.gov (United States)

    Runnova, A. E.; Zhuravlev, M. O.; Koronovskiy, A. A.; Hramov, A. E.

    2017-04-01

    A novel method for removing oculomotor artifacts on electroencephalographical signals is proposed and based on the orthogonal Gram-Schmidt transform using electrooculography data. The method has shown high efficiency removal of artifacts caused by spontaneous movements of the eyeballs (about 95-97% correct remote oculomotor artifacts). This method may be recommended for multi-channel electroencephalography data processing in an automatic on-line in a variety of psycho-physiological experiments.

  16. NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes.

    Science.gov (United States)

    Lin, Chih-Chung; Hsieh, Hsi-Lung; Shih, Ruey-Horng; Chi, Pei-Ling; Cheng, Shin-Ei; Chen, Jin-Chung; Yang, Chuen-Mao

    2012-11-23

    Matrix metalloproteinase-9 (MMP-9) plays a crucial role in pathological processes of brain inflammation, injury, and neurodegeneration. Moreover, bradykinin (BK) induces the expression of several inflammatory proteins in brain astrocytes. Recent studies have suggested that increased oxidative stress is implicated in the brain inflammation and injury. However, whether BK induced MMP-9 expression mediated through oxidative stress remains virtually unknown. Herein we investigated the role of redox signals in BK-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells). In the study, we first demonstrated that reactive oxygen species (ROS) plays a crucial role in BK-induced MMP-9 expression in cultured brain astrocytes (in vitro) and animal brain tissue (in vivo) models. Next, BK-induced MMP-9 expression is mediated through a Ca2+-mediated PKC-α linking to p47phox/NADPH oxidase 2 (Nox2)/ROS signaling pathway. Nox2-dependent ROS generation led to activation and up-regulation of the downstream transcriptional factor AP-1 (i.e. c-Fos and c-Jun), which bound to MMP-9 promoter region, and thereby turned on transcription of MMP-9 gene. Functionally, BK-induced MMP-9 expression enhanced astrocytic migration. These results demonstrated that in RBA-1 cells, activation of AP-1 (c-Fos/c-Jun) by the PKC-α-mediated Nox2/ROS signals is essential for up-regulation of MMP-9 and cell migration enhanced by BK.

  17. NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes

    Directory of Open Access Journals (Sweden)

    Lin Chih-Chung

    2012-11-01

    Full Text Available Abstract Background Matrix metalloproteinase-9 (MMP-9 plays a crucial role in pathological processes of brain inflammation, injury, and neurodegeneration. Moreover, bradykinin (BK induces the expression of several inflammatory proteins in brain astrocytes. Recent studies have suggested that increased oxidative stress is implicated in the brain inflammation and injury. However, whether BK induced MMP-9 expression mediated through oxidative stress remains virtually unknown. Herein we investigated the role of redox signals in BK-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells. Results In the study, we first demonstrated that reactive oxygen species (ROS plays a crucial role in BK-induced MMP-9 expression in cultured brain astrocytes (in vitro and animal brain tissue (in vivo models. Next, BK-induced MMP-9 expression is mediated through a Ca2+-mediated PKC-α linking to p47phox/NADPH oxidase 2 (Nox2/ROS signaling pathway. Nox2-dependent ROS generation led to activation and up-regulation of the downstream transcriptional factor AP-1 (i.e. c-Fos and c-Jun, which bound to MMP-9 promoter region, and thereby turned on transcription of MMP-9 gene. Functionally, BK-induced MMP-9 expression enhanced astrocytic migration. Conclusions These results demonstrated that in RBA-1 cells, activation of AP-1 (c-Fos/c-Jun by the PKC-α-mediated Nox2/ROS signals is essential for up-regulation of MMP-9 and cell migration enhanced by BK.

  18. Repeated intravenous administration of gadobutrol does not lead to increased signal intensity on unenhanced T1-weighted images - a voxel-based whole brain analysis

    Energy Technology Data Exchange (ETDEWEB)

    Langner, Soenke; Kromrey, Marie-Luise [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); Kuehn, Jens-Peter [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); University Hospital, Carl Gustav Carus University Dresden, Institute for Radiology, Dresden (Germany); Grothe, Matthias [University Medicine Greifswald, Department of Neurology, Greifswald (Germany); Domin, Martin [University Medicine Greifswald, Functional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany)

    2017-09-15

    To identify a possible association between repeated intravenous administration of gadobutrol and increased signal intensity in the grey and white matter using voxel-based whole-brain analysis. In this retrospective single-centre study, 217 patients with a clinically isolated syndrome underwent baseline brain magnetic resonance imaging and at least one annual follow-up examination with intravenous administration of 0.1 mmol/kg body weight of gadobutrol. Using the ''Diffeomorphic Anatomical Registration using Exponentiated Lie algebra'' (DARTEL) normalisation process, tissue templates for grey matter (GM), white matter (WM), and cerebrospinal fluid (CSF) were calculated, as were GM-CSF and WM-CSF ratios. Voxel-based whole-brain analysis was used to calculate the signal intensity for each voxel in each data set. Paired t-test was applied to test differences to baseline MRI for significance. Voxel-based whole-brain analysis demonstrated no significant changes in signal intensity of grey and white matter after up to five gadobutrol administrations. There was no significant change in GM-CSF and grey WM-CSF ratios. Voxel-based whole-brain analysis did not demonstrate increased signal intensity of GM and WM on unenhanced T1-weighted images after repeated gadobutrol administration. The molecular structure of gadolinium-based contrast agent preparations may be an essential factor causing SI increase on unenhanced T1-weighted images. (orig.)

  19. Quantification of ethanol methyl (1)H magnetic resonance signal intensity following intravenous ethanol administration in primate brain.

    Science.gov (United States)

    Flory, Graham S; O'Malley, Jean; Grant, Kathleen A; Park, Byung; Kroenke, Christopher D

    2010-03-01

    In vivo(1)H magnetic resonance spectroscopy (MRS) can be used to directly monitor brain ethanol. Previously, studies of human subjects have lead to the suggestion that the ethanol methyl (1)H MRS signal intensity relates to tolerance to ethanol's intoxicating effects. More recently, the ethanol (1)H MRS signal intensity has been recognized to vary between brain gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) due to differences in T(2) within these environments. The methods presented here extend ethanol MRS techniques to non-human primate subjects. Twelve monkeys were administered ethanol while sedated and positioned within a 3T MRI system. Chemical shift imaging (CSI) measurements were performed following intravenous infusion of 1g/kg ethanol. Magnetic resonance imaging (MRI) data were also recorded for each monkey to provide volume fractions of GM, WM, and CSF for each CSI spectrum. To estimate co-variance of ethanol MRS intensity with GM, WM, and CSF volume fractions, the relative contribution of each tissue subtype was determined following corrections for radiofrequency pulse profile non-uniformity, chemical shift artifacts, and differences between the point spread function in the CSI data and the imaging data. The ethanol MRS intensity per unit blood ethanol concentration was found to differ between GM, WM, and CSF. Individual differences in MRS intensity were larger in GM than WM. This methodology demonstrates the feasibility of ethanol MRS experiments and analysis in non-human primate subjects, and suggests GM may be a site of significant variation in ethanol MRS intensity between individuals. Copyright 2009 Elsevier Inc. All rights reserved.

  20. Brain Basics

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    Full Text Available ... Brain Basics will introduce you to some of this science, such as: How the brain develops How ... cell, and responds to signals from the environment; this all helps the cell maintain its balance with ...

  1. Brain Basics

    Medline Plus

    Full Text Available ... the brain How different parts of the brain communicate and work with each other How changes in ... communication signal sent between neurons by which neurons communicate with each other. magnetic resonance imaging (MRI) mdash; ...

  2. Brain Basics

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    Full Text Available ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ... the body's response to stress. impulse —An electrical communication signal sent between neurons by which neurons communicate ...

  3. Brain Basics

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    Full Text Available ... as: How the brain develops How genes and the environment affect the brain The basic structure of the ... leaves the cell, and responds to signals from the environment; this all helps the cell maintain its balance ...

  4. Brain Basics

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    Full Text Available ... control specific body functions such as sleep and speech. The brain continues maturing well into a person's ... as in areas of the brain that control movement. When electrical signals are abnormal, they can cause ...

  5. Activation of sonic hedgehog signaling attenuates oxidized low-density lipoprotein-stimulated brain microvascular endothelial cells dysfunction in vitro.

    Science.gov (United States)

    Jiang, Xiu-Long; Chen, Ting; Zhang, Xu

    2015-01-01

    The study was performed to investigate the role of sonic hedgehog (SHH) in the oxidized low-density lipoprotein (oxLDL)-induced blood-brain barrier (BBB) disruption. The primary mouse brain microvascular endothelial cells (MBMECs) were exposed to oxLDL. The results indicated that treatment of MBMECs with oxLDL decreased the cell viability, and oxidative stress was involved in oxLDL-induce MBMECs dysfunction with increasing intracellular ROS and MDA formation as well as decreasing NO release and eNOS mRNA expression. In addition, SHH signaling components, such as SHH, Smo and Gli1, mRNA and protein levels were significantly decreased after incubation with increasing concentrations of oxLDL. Treatment with oxLDL alone or SHH loss-of-function significantly increased the permeability of MBMECs, and overexpression of SHH attenuated oxLDL-induced elevation of permeability in MBMECs. Furthermore, SHH gain-of-function could reverse oxLDL-induced apoptosis through inhibition caspase3 and caspase8 levels in MBMECs. Taken together, these results demonstrated that the suppression of SHH in MBMECs might contribute to the oxLDL-induced disruption of endothelial barrier. However, the overexpression of SHH could reverse oxLDL-induced endothelial cells dysfunction in vitro.

  6. Effect of cannabis on glutamate signalling in the brain: A systematic review of human and animal evidence.

    Science.gov (United States)

    Colizzi, Marco; McGuire, Philip; Pertwee, Roger G; Bhattacharyya, Sagnik

    2016-05-01

    Use of cannabis or delta-9-tetrahydrocannabinol (Δ9-THC), its main psychoactive ingredient, is associated with psychotic symptoms or disorder. However, the neurochemical mechanism that may underlie this psychotomimetic effect is poorly understood. Although dopaminergic dysfunction is generally recognized as the final common pathway in psychosis, evidence of the effects of Δ9-THC or cannabis use on dopaminergic measures in the brain is equivocal. In fact, it is thought that cannabis or Δ9-THC may not act on dopamine firing directly but indirectly by altering glutamate neurotransmission. Here we systematically review all studies examining acute and chronic effects of cannabis or Δ9-THC on glutamate signalling in both animals and man. Limited research carried out in humans tends to support the evidence that chronic cannabis use reduces levels of glutamate-derived metabolites in both cortical and subcortical brain areas. Research in animals tends to consistently suggest that Δ9-THC depresses glutamate synaptic transmission via CB1 receptor activation, affecting glutamate release, inhibiting receptors and transporters function, reducing enzyme activity, and disrupting glutamate synaptic plasticity after prolonged exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Diffuse light reflectance signals as potential indicators of loss of viability in brain tissue due to hypoxia: charge-coupled-device-based imaging and fiber-based measurement.

    Science.gov (United States)

    Kawauchi, Satoko; Nishidate, Izumi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ashida, Hiroshi; Sato, Shunichi

    2013-01-01

    Brain tissue is highly vulnerable to ischemia/hypoxia, and real-time monitoring of its viability is important. By fiber-based measurements for rat brain, we previously observed a unique triphasic reflectance change (TRC) after a certain period of time after hypoxia. After TRC, rats could not be rescued, suggesting that TRC can be used as an indicator of loss of brain tissue viability. In this study, we investigated this diffuse-reflectance change due to hypoxia in three parts. First, we developed and validated a theoretical method to quantify changes in the absorption and reduced scattering coefficients involved in TRC. Second, we performed charge-coupled-device-based reflectance imaging of the rat brain during hypoxia followed by reoxygenation to examine spatiotemporal characteristics of the reflectance and its correlation with reversibility of brain tissue damage. Third, we made simultaneous imaging and fiber-based measurement of the reflectance for the rat to compare signals obtained by these two modalities. We observed a nontriphasic reflectance change by the imaging, and it was associated with brain tissue viability. We found that TRC measured by the fibers preceded the reflectance-signal change captured by the imaging. This time difference is attributable to the different observation depths in the brain with these two methods.

  8. Representing dispositions

    Directory of Open Access Journals (Sweden)

    Röhl Johannes

    2011-08-01

    Full Text Available Abstract Dispositions and tendencies feature significantly in the biomedical domain and therefore in representations of knowledge of that domain. They are not only important for specific applications like an infectious disease ontology, but also as part of a general strategy for modelling knowledge about molecular interactions. But the task of representing dispositions in some formal ontological systems is fraught with several problems, which are partly due to the fact that Description Logics can only deal well with binary relations. The paper will discuss some of the results of the philosophical debate about dispositions, in order to see whether the formal relations needed to represent dispositions can be broken down to binary relations. Finally, we will discuss problems arising from the possibility of the absence of realizations, of multi-track or multi-trigger dispositions and offer suggestions on how to deal with them.

  9. Brain-Inspired Photonic Signal Processor for Generating Periodic Patterns and Emulating Chaotic Systems

    Science.gov (United States)

    Antonik, Piotr; Haelterman, Marc; Massar, Serge

    2017-05-01

    Reservoir computing is a bioinspired computing paradigm for processing time-dependent signals. Its hardware implementations have received much attention because of their simplicity and remarkable performance on a series of benchmark tasks. In previous experiments, the output was uncoupled from the system and, in most cases, simply computed off-line on a postprocessing computer. However, numerical investigations have shown that feeding the output back into the reservoir opens the possibility of long-horizon time-series forecasting. Here, we present a photonic reservoir computer with output feedback, and we demonstrate its capacity to generate periodic time series and to emulate chaotic systems. We study in detail the effect of experimental noise on system performance. In the case of chaotic systems, we introduce several metrics, based on standard signal-processing techniques, to evaluate the quality of the emulation. Our work significantly enlarges the range of tasks that can be solved by hardware reservoir computers and, therefore, the range of applications they could potentially tackle. It also raises interesting questions in nonlinear dynamics and chaos theory.

  10. The vasopressin receptor of the blood-brain barrier in the rat hippocampus is linked to calcium signalling

    DEFF Research Database (Denmark)

    Hess, J.; Jensen, Claus V.; Diemer, Nils Henrik

    1991-01-01

    Neuropathology, vasopressin receptor, VI subtype, blood-brain barrier, cerebral endothelium, hippocampus, Fura-2......Neuropathology, vasopressin receptor, VI subtype, blood-brain barrier, cerebral endothelium, hippocampus, Fura-2...

  11. Apoptosis Signal-Regulating Kinase 1 Is Involved in Brain-Derived Neurotrophic Factor (BDNF)-Enhanced Cell Motility and Matrix Metalloproteinase 1 Expression in Human Chondrosarcoma Cells

    Science.gov (United States)

    Lin, Chih-Yang; Chang, Sunny Li-Yun; Fong, Yi-Chin; Hsu, Chin-Jung; Tang, Chih-Hsin

    2013-01-01

    Chondrosarcoma is the primary malignancy of bone that is characterized by a potent capacity to invade locally and cause distant metastasis, and is therefore associated with poor prognoses. Chondrosarcoma further shows a predilection for metastasis to the lungs. The brain-derived neurotrophic factor (BDNF) is a small molecule in the neurotrophin family of growth factors that is associated with the disease status and outcome of cancers. However, the effect of BDNF on cell motility in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma cell lines had significantly higher cell motility and BDNF expression compared to normal chondrocytes. We also found that BDNF increased cell motility and expression of matrix metalloproteinase-1 (MMP-1) in human chondrosarcoma cells. BDNF-mediated cell motility and MMP-1 up-regulation were attenuated by Trk inhibitor (K252a), ASK1 inhibitor (thioredoxin), JNK inhibitor (SP600125), and p38 inhibitor (SB203580). Furthermore, BDNF also promoted Sp1 activation. Our results indicate that BDNF enhances the migration and invasion activity of chondrosarcoma cells by increasing MMP-1 expression through a signal transduction pathway that involves the TrkB receptor, ASK1, JNK/p38, and Sp1. BDNF thus represents a promising new target for treating chondrosarcoma metastasis. PMID:23892595

  12. A Hardware-Efficient Scalable Spike Sorting Neural Signal Processor Module for Implantable High-Channel-Count Brain Machine Interfaces.

    Science.gov (United States)

    Yang, Yuning; Boling, Sam; Mason, Andrew J

    2017-08-01

    Next-generation brain machine interfaces demand a high-channel-count neural recording system to wirelessly monitor activities of thousands of neurons. A hardware efficient neural signal processor (NSP) is greatly desirable to ease the data bandwidth bottleneck for a fully implantable wireless neural recording system. This paper demonstrates a complete multichannel spike sorting NSP module that incorporates all of the necessary spike detector, feature extractor, and spike classifier blocks. To meet high-channel-count and implantability demands, each block was designed to be highly hardware efficient and scalable while sharing resources efficiently among multiple channels. To process multiple channels in parallel, scalability analysis was performed, and the utilization of each block was optimized according to its input data statistics and the power, area and/or speed of each block. Based on this analysis, a prototype 32-channel spike sorting NSP scalable module was designed and tested on an FPGA using synthesized datasets over a wide range of signal to noise ratios. The design was mapped to 130 nm CMOS to achieve 0.75 μW power and 0.023 mm2 area consumptions per channel based on post synthesis simulation results, which permits scalability of digital processing to 690 channels on a 4×4 mm2 electrode array.

  13. Fatty acid-induced gut-brain signaling attenuates neural and behavioral effects of sad emotion in humans.

    Science.gov (United States)

    Van Oudenhove, Lukas; McKie, Shane; Lassman, Daniel; Uddin, Bilal; Paine, Peter; Coen, Steven; Gregory, Lloyd; Tack, Jan; Aziz, Qasim

    2011-08-01

    Although a relationship between emotional state and feeding behavior is known to exist, the interactions between signaling initiated by stimuli in the gut and exteroceptively generated emotions remain incompletely understood. Here, we investigated the interaction between nutrient-induced gut-brain signaling and sad emotion induced by musical and visual cues at the behavioral and neural level in healthy nonobese subjects undergoing functional magnetic resonance imaging. Subjects received an intragastric infusion of fatty acid solution or saline during neutral or sad emotion induction and rated sensations of hunger, fullness, and mood. We found an interaction between fatty acid infusion and emotion induction both in the behavioral readouts (hunger, mood) and at the level of neural activity in multiple pre-hypothesized regions of interest. Specifically, the behavioral and neural responses to sad emotion induction were attenuated by fatty acid infusion. These findings increase our understanding of the interplay among emotions, hunger, food intake, and meal-induced sensations in health, which may have important implications for a wide range of disorders, including obesity, eating disorders, and depression.

  14. Brain expressed and X-linked (Bex proteins are intrinsically disordered proteins (IDPs and form new signaling hubs.

    Directory of Open Access Journals (Sweden)

    Eva M Fernandez

    Full Text Available Intrinsically disordered proteins (IDPs are abundant in complex organisms. Due to their promiscuous nature and their ability to adopt several conformations IDPs constitute important points of network regulation. The family of Brain Expressed and X-linked (Bex proteins consists of 5 members in humans (Bex1-5. Recent reports have implicated Bex proteins in transcriptional regulation and signaling pathways involved in neurodegeneration, cancer, cell cycle and tumor growth. However, structural and biophysical data for this protein family is almost non-existent. We used bioinformatics analyses to show that Bex proteins contain long regions of intrinsic disorder which are conserved across all members. Moreover, we confirmed the intrinsic disorder by circular dichroism spectroscopy of Bex1 after expression and purification in E. coli. These observations strongly suggest that Bex proteins constitute a new group of IDPs. Based on these findings, together with the demonstrated promiscuity of Bex proteins and their involvement in different signaling pathways, we propose that Bex family members play important roles in the formation of protein network hubs.

  15. Effects of chronic methamphetamine on psychomotor and cognitive functions and dopamine signaling in the brain.

    Science.gov (United States)

    Thanos, Panayotis K; Kim, Ronald; Delis, Foteini; Rocco, Mark J; Cho, Jacob; Volkow, Nora D

    2017-03-01

    Methamphetamine (MA) studies in animals usually involve acute, binge, or short-term exposure to the drug. However, addicts take substantial amounts of MA for extended periods of time. Here we wished to study the effects of MA exposure on brain and behavior, using an animal model analogous to this pattern of MA intake. MA doses, 4 and 8mg/kg/day, were based on previously reported average daily freely available MA self-administration levels. We examined the effects of 16 week MA treatment on psychomotor and cognitive function in the rat using open field and novel object recognition tests and we studied the adaptations of the dopaminergic system, using in vitro and in vivo receptor imaging. We show that chronic MA treatment, at doses that correspond to the average daily freely available self-administration levels in the rat, disorganizes open field activity, impairs alert exploratory behavior and anxiety-like state, and downregulates dopamine transporter in the striatum. Under these treatment conditions, dopamine terminal functional integrity in the nucleus accumbens is also affected. In addition, lower dopamine D1 receptor binding density, and, to a smaller degree, lower dopamine D2 receptor binding density were observed. Potential mechanisms related to these alterations are discussed. Copyright © 2016. Published by Elsevier B.V.

  16. Massively parallel signal processing using the graphics processing unit for real-time brain-computer interface feature extraction

    Directory of Open Access Journals (Sweden)

    J. Adam Wilson

    2009-07-01

    Full Text Available The clock speeds of modern computer processors have nearly plateaued in the past five years. Consequently, neural prosthetic systems that rely on processing large quantities of data in a short period of time face a bottleneck, in that it may not be possible to process all of the data recorded from an electrode array with high channel counts and bandwidth, such as electrocorticographic grids or other implantable systems. Therefore, in this study a method of using the processing capabilities of a graphics card (GPU was developed for real-time neural signal processing of a brain-computer interface (BCI. The NVIDIA CUDA system was used to offload processing to the GPU, which is capable of running many operations in parallel, potentially greatly increasing the speed of existing algorithms. The BCI system records many channels of data, which are processed and translated into a control signal, such as the movement of a computer cursor. This signal processing chain involves computing a matrix-matrix multiplication (i.e., a spatial filter, followed by calculating the power spectral density on every channel using an auto-regressive method, and finally classifying appropriate features for control. In this study, the first two computationally-intensive steps were implemented on the GPU, and the speed was compared to both the current implementation and a CPU-based implementation that uses multi-threading. Significant performance gains were obtained with GPU processing: the current implementation processed 1000 channels in 933 ms, while the new GPU method took only 27 ms, an improvement of nearly 35 times.

  17. Massively Parallel Signal Processing using the Graphics Processing Unit for Real-Time Brain-Computer Interface Feature Extraction.

    Science.gov (United States)

    Wilson, J Adam; Williams, Justin C

    2009-01-01

    The clock speeds of modern computer processors have nearly plateaued in the past 5 years. Consequently, neural prosthetic systems that rely on processing large quantities of data in a short period of time face a bottleneck, in that it may not be possible to process all of the data recorded from an electrode array with high channel counts and bandwidth, such as electrocorticographic grids or other implantable systems. Therefore, in this study a method of using the processing capabilities of a graphics card [graphics processing unit (GPU)] was developed for real-time neural signal processing of a brain-computer interface (BCI). The NVIDIA CUDA system was used to offload processing to the GPU, which is capable of running many operations in parallel, potentially greatly increasing the speed of existing algorithms. The BCI system records many channels of data, which are processed and translated into a control signal, such as the movement of a computer cursor. This signal processing chain involves computing a matrix-matrix multiplication (i.e., a spatial filter), followed by calculating the power spectral density on every channel using an auto-regressive method, and finally classifying appropriate features for control. In this study, the first two computationally intensive steps were implemented on the GPU, and the speed was compared to both the current implementation and a central processing unit-based implementation that uses multi-threading. Significant performance gains were obtained with GPU processing: the current implementation processed 1000 channels of 250 ms in 933 ms, while the new GPU method took only 27 ms, an improvement of nearly 35 times.

  18. Cabergoline, a dopamine receptor agonist, has an antidepressant-like property and enhances brain-derived neurotrophic factor signaling.

    Science.gov (United States)

    Chiba, Shuichi; Numakawa, Tadahiro; Ninomiya, Midori; Yoon, Hyung Shin; Kunugi, Hiroshi

    2010-08-01

    Dopamine agonists have been implicated in the treatment of depression. Cabergoline is an ergot derivative with a high affinity to dopamine D(2)-like receptors; however, there have been few preclinical studies on its antidepressant-like effects. Behavioral effects of cabergoline were examined in rats using forced swimming (FST), novelty-suppressed feeding (NST), open field (OFT), and elevated-plus maze (EPT) tests. In a single treatment paradigm, behaviors of rats were analyzed 4 h after single injection of cabergoline (s.c., 0-4 micromol/kg). In a repeated-treatment paradigm, OFT, EPT, and FST were conducted on days 11, 12, and 13-14, respectively, during daily cabergoline injections (s.c., 0.5 micromol/kg), and then hippocampus was removed 24 h after the last injection. NST was conducted in a separate experiment at day 14. Western blotting was used for the analysis of the protein levels of brain-derived neurotrophic factor (BDNF) and the activation of intracellular signaling molecules. Single injection of cabergoline demonstrated decreased immobility in FST and distance traveled during 0-10 min in OFT, while time spent and entry into open arms were increased at 4 micromol/kg. When cabergoline was repeatedly administered, immobility in FST and the latency of feeding in NSF were significantly reduced, while vertical movement was increased in OFT. The time in closed arms was tended to be decreased in EPT. Expression of BDNF and activation of extracellular signal-regulated kinase 1 were up-regulated after the chronic administration of cabergoline. Cabergoline exerts antidepressant- and anxiolytic-like effects, which may be mediated by potentiation of intracellular signaling of BDNF.

  19. Signaling through MyD88 regulates leukocyte recruitment after brain injury

    DEFF Research Database (Denmark)

    Babcock, Alicia A; Toft-Hansen, Henrik; Owens, Trevor

    2008-01-01

    Injury to the CNS provokes an innate inflammatory reaction that engages infiltrating leukocytes with the capacity to repair and/or exacerbate tissue damage. The initial cues that orchestrate leukocyte entry remain poorly defined. We have used flow cytometry to investigate whether MyD88, an adaptor...... protein that transmits signals from TLRs and receptors for IL-1 and IL-18, regulates leukocyte infiltration into the stab-injured entorhinal cortex (EC) and into sites of axonal degeneration in the denervated hippocampus. We have previously established the kinetics of leukocyte entry into the denervated...... hippocampus. We now show that significant leukocyte entry into the EC occurs within 3-12 h of stab injury. Whereas T cells showed small, gradual increases over 8 days, macrophage infiltration was pronounced and peaked within 12-24 h. MyD88 deficiency significantly reduced macrophage and T cell recruitment...

  20. Kinesthetic imagery training of forceful muscle contractions increases brain signal and muscle strength.

    Science.gov (United States)

    Yao, Wan X; Ranganathan, Vinoth K; Allexandre, Didier; Siemionow, Vlodek; Yue, Guang H

    2013-01-01

    The purpose of this study was to compare the effect of training using internal imagery (IMI; also known as kinesthetic imagery or first person imagery) with that of external imagery (EMI; also known as third-person visual imagery) of strong muscle contractions on voluntary muscle strengthening. Eighteen young, healthy subjects were randomly assigned to one of three groups (6 in each group): internal motor imagery (IMI), external motor imagery (EMI), or a no-practice control (CTRL) group. Training lasted for 6 weeks (~15 min/day, 5 days/week). The participants' right arm elbow-flexion strength, muscle electrical activity, and movement-related cortical potential (MRCP) were evaluated before and after training. Only the IMI group showed significant strength gained (10.8%) while the EMI (4.8%) and CTRL (-3.3%) groups did not. Only the IMI group showed a significant elevation in MRCP on scalp locations over both the primary motor (M1) and supplementary motor cortices (EMI group over M1 only) and this increase was significantly greater than that of EMI and CTRL groups. These results suggest that training by IMI of forceful muscle contractions was effective in improving voluntary muscle strength without physical exercise. We suggest that the IMI training likely strengthened brain-to-muscle (BTM) command that may have improved motor unit recruitment and activation, and led to greater muscle output. Training by IMI of forceful muscle contractions may change the activity level of cortical motor control network, which may translate into greater descending command to the target muscle and increase its strength.

  1. KINESTHETIC IMAGERY TRAINING OF FORCEFUL MUSCLE CONTRACTIONS INCREASES BRAIN SIGNAL AND MUSCLE STRENGTH

    Directory of Open Access Journals (Sweden)

    Wan X Yao

    2013-09-01

    Full Text Available The purpose of this study was to compare the effect of training using internal imagery (IMI; also known as kinesthetic imagery or first person imagery with that of external imagery (EMI; also known as third-person visual imagery of strong muscle contractions on voluntary muscle strengthening. Eighteen young, healthy subjects were randomly assigned to one of three groups (6 in each group: internal motor imagery (IMI, external motor imagery (EMI, or a no-practice control (CTRL group. Training lasted for 6 weeks (~15 min/day, 5 days/week. The participants’ right arm elbow-flexion strength, muscle electrical activity and movement-related cortical potential (MRCP were evaluated before and after training. Only the IMI group showed significant strength gained (10.8% while the EMI (4.8% and CTRL (-3.3% groups did not. Only the IMI group showed a significant elevation in MRCP on scalp locations over both the primary motor (M1 and supplementary motor cortices (EMI group over M1 only and this increase was significantly greater than that of EMI and CTRL groups. These results suggest that training by IMI of forceful muscle contractions was effective in improving voluntary muscle strength without physical exercise. We suggest that the IMI training likely strengthened brain-to-muscle (BTM command that may have improved motor unit recruitment and activation, and led to greater muscle output. Training by internal motor imagery of forceful muscle contractions may change the activity level of cortical motor control network, which may translate into greater descending command to the target muscle and increase its strength.

  2. Representing Development

    DEFF Research Database (Denmark)

    Representing Development presents the different social representations that have formed the idea of development in Western thinking over the past three centuries. Offering an acute perspective on the current state of developmental science and providing constructive insights into future pathways...... and development, addressing their contemporary enactments and reflecting on future theoretical and empirical directions. The first section of the book provides an historical account of early representations of development that, having come from life science, has shaped the way in which developmental science has...... approached development. Section two focuses upon the contemporary issues of developmental psychology, neuroscience and developmental science at large. The final section offers a series of commentaries pointing to the questions opened by the previous chapters, looking to outline the future lines...

  3. Brain Basics

    Medline Plus

    Full Text Available ... neuron's point of contact for receiving chemical and electrical signals called impulses from neighboring neurons. Axon which ... from one neuron to another as chemical or electrical signals. The brain begins as a small group ...

  4. Functional MRI signal fluctuations highlight altered resting brain activity in Huntington's disease.

    Science.gov (United States)

    Sarappa, Chiara; Salvatore, Elena; Filla, Alessandro; Cocozza, Sirio; Russo, Cinzia Valeria; Saccà, Francesco; Brunetti, Arturo; De Michele, Giuseppe; Quarantelli, Mario

    2017-10-01

    The fractional Amplitude of Low Frequency Fluctuations (fALFF) and the degree of local synchronization (Regional Homogeneity - ReHo) of resting-state BOLD signal have been suggested to map spontaneous neuronal activity and local functional connectivity, respectively. We compared voxelwise, independent of atrophy, the fALFF and ReHo patterns of 11 presymptomatic (ps-HD) and 28 symptomatic (sHD) Huntington's disease mutation carriers, with those of 40 normal volunteers, and tested their possible correlations with the motor and cognitive subscores of the Unified Huntington's Disease Rating Scale. In sHD patients, fALFF was mainly reduced bilaterally in parietal lobes (right precuneus being already affected in psHD), and in superior frontal gyri, and increased bilaterally in cerebellar lobules VI, VIII and IX, as well as in the right inferior temporal gyrus. In sHD, and to a lesser extent in psHD, ReHo was bilaterally reduced in putamina, cerebellar lobules III to VI, and superior medial frontal gyri, and increased in both psHD and sHD in fronto-basal cortices, and in the right temporal lobe. fALFF correlated inversely with cognitive scores in lobule IX of the cerebellum (mainly with total Stroop score, p Huntington's Disease, and with reduced local functional integration in subcortical and cerebellar components of the sensori-motor network. Cerebellar clusters of significant correlation of fALFF with executive function scores may be related to compensatory mechanisms.

  5. Structures of the first representatives of Pfam family PF06938 (DUF1285) reveal a new fold with repeated structural motifs and possible involvement in signal transduction.

    Science.gov (United States)

    Han, Gye Won; Bakolitsa, Constantina; Miller, Mitchell D; Kumar, Abhinav; Carlton, Dennis; Najmanovich, Rafael J; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L; Chen, Connie; Chiu, Hsiu Ju; Clayton, Thomas; Das, Debanu; Deller, Marc C; Duan, Lian; Ernst, Dustin; Feuerhelm, Julie; Grant, Joanna C; Grzechnik, Anna; Jaroszewski, Lukasz; Jin, Kevin K; Johnson, Hope A; Klock, Heath E; Knuth, Mark W; Kozbial, Piotr; Krishna, S Sri; Marciano, David; McMullan, Daniel; Morse, Andrew T; Nigoghossian, Edward; Okach, Linda; Reyes, Ron; Rife, Christopher L; Sefcovic, Natasha; Tien, Henry J; Trame, Christine B; van den Bedem, Henry; Weekes, Dana; Xu, Qingping; Hodgson, Keith O; Wooley, John; Elsliger, Marc André; Deacon, Ashley M; Godzik, Adam; Lesley, Scott A; Wilson, Ian A

    2010-10-01

    The crystal structures of SPO0140 and Sbal_2486 were determined using the semiautomated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). The structures revealed a conserved core with domain duplication and a superficial similarity of the C-terminal domain to pleckstrin homology-like folds. The conservation of the domain interface indicates a potential binding site that is likely to involve a nucleotide-based ligand, with genome-context and gene-fusion analyses additionally supporting a role for this family in signal transduction, possibly during oxidative stress.

  6. Purinergic signaling induces cyclooxygenase-1-dependent prostanoid synthesis in microglia: roles in the outcome of excitotoxic brain injury.

    Directory of Open Access Journals (Sweden)

    Josef Anrather

    Full Text Available Cyclooxygenases (COX are prostanoid synthesizing enzymes constitutively expressed in the brain that contribute to excitotoxic neuronal cell death. While the neurotoxic role of COX-2 is well established and has been linked to prostaglandin E(2 synthesis, the role of COX-1 is not clearly understood. In a model of N-Methyl-D-aspartic acid (NMDA induced excitotoxicity in the mouse cerebral cortex we found a distinctive temporal profile of COX-1 and COX-2 activation where COX-1, located in microglia, is responsible for the early phase of prostaglandin E(2 synthesis (10 minutes after NMDA, while both COX-1 and COX-2 contribute to the second phase (3-24 hours after NMDA. Microglial COX-1 is strongly activated by ATP but not excitatory neurotransmitters or the Toll-like receptor 4 ligand bacterial lipopolysaccharide. ATP induced microglial COX-1 dependent prostaglandin E(2 synthesis is dependent on P2X7 receptors, extracellular Ca(2+ and cytoplasmic phospholipase A2. NMDA receptor activation induces ATP release from cultured neurons leading to microglial P2X7 receptor activation and COX-1 dependent prostaglandin E(2 synthesis in mixed microglial-neuronal cultures. Pharmacological inhibition of COX-1 has no effect on the cortical lesion produced by NMDA, but counteracts the neuroprotection exerted by inhibition of COX-2 or observed in mice lacking the prostaglandin E(2 receptor type 1. Similarly, the neuroprotection exerted by the prostaglandin E(2 receptor type 2 agonist butaprost is not observed after COX-1 inhibition. P2X7 receptors contribute to NMDA induced prostaglandin E(2 production in vivo and blockage of P2X7 receptors reverses the neuroprotection offered by COX-2 inhibition. These findings suggest that purinergic signaling in microglia triggered by neuronal ATP modulates excitotoxic cortical lesion by regulating COX-1 dependent prostanoid production and unveil a previously unrecognized protective role of microglial COX-1 in excitotoxic brain

  7. Effects of chronic Δ9-tetrahydrocannabinol treatment on Rho/Rho-kinase signalization pathway in mouse brain

    Directory of Open Access Journals (Sweden)

    Halil Mahir Kaplan

    2017-11-01

    Full Text Available Δ9-Tetrahydrocannabinol (Δ9-THC shows its effects by activating cannabinoid receptors which are on some tissues and neurons. Cannabinoid systems have role on cell proliferation and development of neurons. Furthermore, it is interesting that cannabinoid system and rho/rho-kinase signalization pathway, which have important role on cell development and proliferation, may have role on neuron proliferation and development together. Thus, a study is planned to investigate rhoA and rho-kinase enzyme expressions and their activities in the brain of chronic Δ9-THC treated mice. One group of mice are treated with Δ9-THC once to see effects of acute treatment. Another group of mice are treated with Δ9-THC three times per day for one month. After this period, rhoA and rho-kinase enzyme expressions and their activities in mice brains are analyzed by ELISA method. Chronic administration of Δ9-THC decreased the expression of rhoA while acute treatment has no meaningful effect on it. Administration of Δ9-THC did not affect expression of rho-kinase on both chronic and acute treatment. Administration of Δ9-THC increased rho-kinase activity on both chronic and acute treatment, however, chronic treatment decreased its activity with respect to acute treatment. This study showed that chronic Δ9-THC treatment down-regulated rhoA expression and did not change the expression level of rho-kinase which is downstream effector of rhoA. However, it elevated the rho-kinase activity. Δ9-THC induced down-regulation of rhoA may cause elevation of cypin expression and may have benefit on cypin related diseases. Furthermore, use of rho-kinase inhibitors and Δ9-THC together can be useful on rho-kinase related diseases.

  8. Effect of short-term exercise training on brain-derived neurotrophic factor signaling in spontaneously hypertensive rats.

    Science.gov (United States)

    Monnier, Alice; Garnier, Philippe; Quirie, Aurore; Pernet, Nicolas; Demougeot, Céline; Marie, Christine; Prigent-Tessier, Anne

    2017-02-01

    Decreased brain-derived neurotrophic factor (BDNF) level has been reported in the hippocampus of hypertensive rats. The present study explored whether brain neurons and/or endothelial cells are targeted by hypertension with respect to BDNF expression and the potential of physical exercise to cope with hypertension. Physical exercise was induced in spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats. The hippocampus of sedentary and exercised rats (n = 6 for each group) were used for western blots to assess proBDNF, mature BDNF (mBDNF), tropomyosin-related kinase B (TrkB), P-TrkB (TrkB phosphorylated at tyrosine 816), synaptophysin, endothelial nitric oxide synthase (eNOS) and eNOS phosphorylated at serine 1177 protein levels. BDNF and proBDNF localization in the hippocampus was studied in WKY rats, SHR and exercised SHR (n = 5 each). mBDNF and proBDNF protein levels were also assessed in hippocampal slices prepared from SHR (n = 10) that were incubated for 24 h with the nitric oxide (NO) donor glyceryl trinitrate. SBP was measured by the tail-cuff method. Exercise modified blood pressure neither in SHR nor WKY. As compared with WKY rats, SHR displayed decreased levels of mBDNF, P-TrkB, synaptophysin, eNOS and eNOS phosphorylated at serine 1177 but no change in proBDNF and TrkB levels. These effects coincided with low BDNF staining in both endothelial cells and neurons. Exercise improved the endothelium-derived NO system and the BDNF pathway in both strains. The NO donor increased mBDNF but decreased proBDNF levels. Our results revealed that endothelial and neuronal BDNF expressions were both impaired in hypertension and that physical exercise improved hippocampal mBDNF levels and signaling through blood pressure-independent mechanisms.

  9. Immune challenge by intraperitoneal administration of lipopolysaccharide directs gene expression in distinct blood-brain barrier cells toward enhanced prostaglandin E(2) signaling.

    Science.gov (United States)

    Vasilache, Ana Maria; Qian, Hong; Blomqvist, Anders

    2015-08-01

    The cells constituting the blood-brain barrier are critical for the transduction of peripheral immune signals to the brain, but hitherto no comprehensive analysis of the signaling events that occur in these cells in response to a peripheral inflammatory stimulus has been performed. Here, we examined the inflammatory transcriptome in blood-brain barrier cells, including endothelial cells, pericytes, and perivascular macrophages, which were isolated by fluorescent-activated cell sorting, from non-immune-challenged mice and from mice stimulated by bacterial wall lipopolysaccharide. We show that endothelial cells and perivascular macrophages display distinct transcription profiles for inflammatory signaling and respond in distinct and often opposing ways to the immune stimulus. Thus, endothelial cells show induced PGE2 synthesis and transport with attenuation of PGE2 catabolism, increased expression of cytokine receptors and down-stream signaling molecules, and downregulation of adhesion molecules. In contrast, perivascular macrophages show downregulation of the synthesis of prostanoids other than PGE2 and of prostaglandin catabolism, but upregulation of interleukin-6 synthesis. Pericytes were largely unresponsive to the immune stimulation, with the exception of downregulation of proteins involved in pericyte-endothelial cell communication. While the endothelial cells account for most of the immune-induced gene expression changes in the blood-brain barrier, the response of the endothelial cells occurs in a concerted manner with that of the perivascular cells to elevate intracerebral levels of PGE2, hence emphasizing the critical role of PGE2 in immune-induced signal transduction across the blood-brain barrier. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Signaling proteins are represented in tissue fluid/lymph from soft tissues of normal human legs at concentrations different from serum.

    Science.gov (United States)

    Zaleska, Marzanna; Olszewski, Waldemar L; Durlik, Marek; Miller, Norman E

    2013-12-01

    The mobile intercellular fluid flowing to and in the lymphatics contains filtered plasma products and substances synthesized and excreted by tissue cells. Among them are signaling proteins such as cytokines, chemokines, enzymes, and growth factors. They act locally in autocrine and paracrine systems regulating cell metabolism, proliferation, and formation of the ground matrix. They play an immunoregulatory role in infections, wound healing, and tumor cell growth. In this study we measured the concentration of selected cytokines, chemokines, tissue enzymes, and growth factors in tissue fluid/lymph drained from normal human leg soft tissues. Legs exposed to infections and trauma often result in development of lymphedema. Lymph was drained from superficial calf lymphatics using microsurgical techniques. Our studies showed generally higher concentrations of cytokines, chemokines, enzymes, and growth factors in lymph than in serum. The total protein L/S ratio was 0.22, whereas that of various lymph signaling proteins ranged between 1 and 10. This indicates that in addition to proteins filtered from blood, local cells contribute to lymph concentration by own production, depending on the actual cell requirement. Moreover, there were major individual differences of lymph levels with simultaneous stable serum levels. This suggests existence of a local autonomous regulatory humoral mechanism in tissues, not reflected in serum.

  11. Cross Talk Between Brain Innate Immunity and Serotonin Signaling Underlies Depressive-Like Behavior Induced by Alzheimer's Amyloid-β Oligomers in Mice.

    Science.gov (United States)

    Ledo, Jose Henrique; Azevedo, Estefania P; Beckman, Danielle; Ribeiro, Felipe C; Santos, Luis E; Razolli, Daniela S; Kincheski, Grasielle C; Melo, Helen M; Bellio, Maria; Teixeira, Antonio L; Velloso, Licio A; Foguel, Debora; De Felice, Fernanda G; Ferreira, Sergio T

    2016-11-30

    Considerable clinical and epidemiological evidence links Alzheimer's disease (AD) and depression. However, the molecular mechanisms underlying this connection are largely unknown. We reported recently that soluble Aβ oligomers (AβOs), toxins that accumulate in AD brains and are thought to instigate synapse damage and memory loss, induce depressive-like behavior in mice. Here, we report that the mechanism underlying this action involves AβO-induced microglial activation, aberrant TNF-α signaling, and decreased brain serotonin levels. Inactivation or ablation of microglia blocked the increase in brain TNF-α and abolished depressive-like behavior induced by AβOs. Significantly, we identified serotonin as a negative regulator of microglial activation. Finally, AβOs failed to induce depressive-like behavior in Toll-like receptor 4-deficient mice and in mice harboring a nonfunctional TLR4 variant in myeloid cells. Results establish that AβOs trigger depressive-like behavior via a double impact on brain serotonin levels and microglial activation, unveiling a cross talk between brain innate immunity and serotonergic signaling as a key player in mood alterations in AD. Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the main cause of dementia in the world. Brain accumulation of amyloid-β oligomers (AβOs) is a major feature in the pathogenesis of AD. Although clinical and epidemiological data suggest a strong connection between AD and depression, the underlying mechanisms linking these two disorders remain largely unknown. Here, we report that aberrant activation of the brain innate immunity and decreased serotonergic tonus in the brain are key players in AβO-induced depressive-like behavior in mice. Our findings may open up new possibilities for the development of effective therapeutics for AD and depression aimed at modulating microglial function. Copyright © 2016 the authors 0270-6474/16/3612106-11$15.00/0.

  12. Quaternion-Based Signal Analysis for Motor Imagery Classification from Electroencephalographic Signals

    Science.gov (United States)

    Batres-Mendoza, Patricia; Montoro-Sanjose, Carlos R.; Guerra-Hernandez, Erick I.; Almanza-Ojeda, Dora L.; Rostro-Gonzalez, Horacio; Romero-Troncoso, Rene J.; Ibarra-Manzano, Mario A.

    2016-01-01

    Quaternions can be used as an alternative to model the fundamental patterns of electroencephalographic (EEG) signals in the time domain. Thus, this article presents a new quaternion-based technique known as quaternion-based signal analysis (QSA) to represent EEG signals obtained using a brain-computer interface (BCI) device to detect and interpret cognitive activity. This quaternion-based signal analysis technique can extract features to represent brain activity related to motor imagery accurately in various mental states. Experimental tests in which users where shown visual graphical cues related to left and right movements were used to collect BCI-recorded signals. These signals were then classified using decision trees (DT), support vector machine (SVM) and k-nearest neighbor (KNN) techniques. The quantitative analysis of the classifiers demonstrates that this technique can be used as an alternative in the EEG-signal modeling phase to identify mental states. PMID:26959029

  13. Quaternion-Based Signal Analysis for Motor Imagery Classification from Electroencephalographic Signals.

    Science.gov (United States)

    Batres-Mendoza, Patricia; Montoro-Sanjose, Carlos R; Guerra-Hernandez, Erick I; Almanza-Ojeda, Dora L; Rostro-Gonzalez, Horacio; Romero-Troncoso, Rene J; Ibarra-Manzano, Mario A

    2016-03-05

    Quaternions can be used as an alternative to model the fundamental patterns of electroencephalographic (EEG) signals in the time domain. Thus, this article presents a new quaternion-based technique known as quaternion-based signal analysis (QSA) to represent EEG signals obtained using a brain-computer interface (BCI) device to detect and interpret cognitive activity. This quaternion-based signal analysis technique can extract features to represent brain activity related to motor imagery accurately in various mental states. Experimental tests in which users where shown visual graphical cues related to left and right movements were used to collect BCI-recorded signals. These signals were then classified using decision trees (DT), support vector machine (SVM) and k-nearest neighbor (KNN) techniques. The quantitative analysis of the classifiers demonstrates that this technique can be used as an alternative in the EEG-signal modeling phase to identify mental states.

  14. Brain-mediated antidiabetic, anorexic, and cardiovascular actions of leptin require melanocortin-4 receptor signaling.

    Science.gov (United States)

    da Silva, Alexandre A; Spradley, Frank T; Granger, Joey P; Hall, John E; do Carmo, Jussara M

    2015-04-01

    We previously demonstrated that leptin has powerful central nervous system (CNS)-mediated antidiabetic actions. In this study we tested the importance of melanocortin-4 receptors (MC4Rs) for leptin's ability to suppress food intake, increase blood pressure (BP) and heart rate (HR), and normalize glucose levels in insulin-dependent diabetes. MC4R knockout (MC4R-KO) and control wild-type (WT) rats were implanted with intracerebroventricular (ICV) cannula and BP and HR were measured 24 h/day by telemetry. After 5-day control period, an injection of streptozotocin (50 mg/kg, ip) was used to induce diabetes. Eight days after injection, an osmotic pump was implanted subcutaneously and connected to the ICV cannula to deliver leptin (15 μg/day) for 7 days. At baseline, MC4R-KO rats were hyperphagic and 40% heavier than WT rats. Despite obesity, BP was similar (112 ± 2 vs. 111 ± 2 mmHg) and HR was lower in MC4R-KO rats (320 ± 6 vs. 347 ± 5 beats/min). Induction of diabetes increased food intake (30%) and reduced BP (∼17 mmHg) and HR (∼61 beats/min) in WT rats, while food intake, BP, and HR were reduced by ∼10%, 7 mmHg, and 33 beats/min, respectively, in MC4R-KO rats. Leptin treatment normalized blood glucose (437 ± 10 to 136 ± 18 mg/dl), reduced food intake (40%), and increased HR (+60 beats/min) and BP (+9 mmHg) in WT rats. Only modest changes in blood glucose (367 ± 16 to 326 ± 23 mg/dl), food intake (5%), HR (+16 beats/min) and BP (+4 mmHg) were observed in MC4R-KO rats. These results indicate that intact CNS MC4R signaling is necessary for leptin to exert its chronic antidiabetic, anorexic, and cardiovascular actions. Copyright © 2015 the American Physiological Society.

  15. Statistical approach of measurement of signal to noise ratio in according to change pulse sequence on brain MRI meningioma and cyst images

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eul Kyu [Inje Paik University Hospital Jeo-dong, Seoul (Korea, Republic of); Choi, Kwan Woo [Asan Medical Center, Seoul (Korea, Republic of); Jeong, Hoi Woun [The Baekseok Culture University, Cheonan (Korea, Republic of); Jang, Seo Goo [The Soonchunhyang University, Asan (Korea, Republic of); Kim, Ki Won [Kyung Hee University Hospital at Gang-dong, Seoul (Korea, Republic of); Son, Soon Yong [The Wonkwang Health Science University, Iksan (Korea, Republic of); Min, Jung Whan; Son, Jin Hyun [The Shingu University, Sungnam (Korea, Republic of)

    2016-09-15

    The purpose of this study was to needed basis of measure MRI CAD development for signal to noise ratio (SNR) by pulse sequence analysis from region of interest (ROI) in brain magnetic resonance imaging (MRI) contrast. We examined images of brain MRI contrast enhancement of 117 patients, from January 2005 to December 2015 in a University-affiliated hospital, Seoul, Korea. Diagnosed as one of two brain diseases such as meningioma and cysts SNR for each patient's image of brain MRI were calculated by using Image J. Differences of SNR among two brain diseases were tested by SPSS Statistics21 ANOVA test for there was statistical significance (p < 0.05). We have analysis socio-demographical variables, SNR according to sequence disease, 95% confidence according to SNR of sequence and difference in a mean of SNR. Meningioma results, with the quality of distributions in the order of T1CE, T2 and T1, FLAIR. Cysts results, with the quality of distributions in the order of T2 and T1, T1CE and FLAIR. SNR of MRI sequences of the brain would be useful to classify disease. Therefore, this study will contribute to evaluate brain diseases, and be a fundamental to enhancing the accuracy of CAD development.

  16. Decoupled temporal variability and signal synchronization of spontaneous brain activity in loss of consciousness: An fMRI study in anesthesia.

    Science.gov (United States)

    Huang, Zirui; Zhang, Jun; Wu, Jinsong; Qin, Pengmin; Wu, Xuehai; Wang, Zhiyao; Dai, Rui; Li, Yuan; Liang, Weimin; Mao, Ying; Yang, Zhong; Zhang, Jianfeng; Wolff, Annemarie; Northoff, Georg

    2016-01-01

    Two aspects of the low frequency fluctuations of spontaneous brain activity have been proposed which reflect the complex and dynamic features of resting-state activity, namely temporal variability and signal synchronization. The relationship between them, especially its role in consciousness, nevertheless remains unclear. Our study examined the temporal variability and signal synchronization of spontaneous brain activity, as well as their relationship during loss of consciousness. We applied an intra-subject design of resting-state functional magnetic resonance imaging (rs-fMRI) in two conditions: during wakefulness, and under anesthesia with clinical unconsciousness. In addition, an independent group of patients with disorders of consciousness (DOC) was included in order to test the reliability of our findings. We observed a global reduction in the temporal variability, local and distant brain signal synchronization for subjects during anesthesia. Importantly, we found a link between temporal variability and both local and distant signal synchronizations during wakefulness: the higher the degree of temporal variability, the higher its intra-regional homogeneity and inter-regional functional connectivity. In contrast, this link was broken down under anesthesia, implying a decoupling between temporal variability and signal synchronization; this decoupling was reproduced in patients with DOC. Our results suggest that there exist some as yet unclear physiological mechanisms of consciousness which "couple" the two mathematically independent measures, temporal variability and signal synchronization of spontaneous brain activity. Our findings not only extend our current knowledge of the neural correlates of anesthetic-induced unconsciousness, but have implications for both computational neural modeling and clinical practice, such as in the diagnosis of loss of consciousness in patients with DOC. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Altered Wnt signalling in the teenage suicide brain: focus on glycogen synthase kinase-3β and β-catenin.

    Science.gov (United States)

    Ren, Xinguo; Rizavi, Hooriyah S; Khan, Mansoor A; Dwivedi, Yogesh; Pandey, Ghanshyam N

    2013-06-01

    Glycogen synthase kinase (GSK)-3β and β-catenin are important components of the Wnt signalling pathway, which is involved in numerous physiological functions such as cognition, brain development and cell survival. Their abnormalities have been implicated in mood disorders and schizophrenia. Teenage suicide is a major public health concern; however, very little is known about its neurobiology. In order to examine if abnormalities of GSK-3β and β-catenin are associated with teenage suicide, we determined the gene and protein expression of GSK-3β and β-catenin in the prefrontal cortex (PFC) and hippocampus obtained from 24 teenage suicide victims and 24 normal control subjects. Protein expression was determined using Western blot with specific antibodies and gene expression (mRNA levels) was determined using the real-time polymerase chain reaction method. No significant change was observed in the GSK-3β protein levels either in the PFC or hippocampus of suicide victims compared to controls. However, protein levels of pGSK-3β-ser(9) were significantly decreased in the PFC and hippocampus of suicide victims compared to normal controls. We also found that GSK-3β mRNA levels were significantly decreased in the PFC but not in the hippocampus of teenage suicide victims compared to controls. Mean protein and mRNA levels of β-catenin were significantly decreased in both the PFC and hippocampus of teenage suicide group compared to controls. The observation that there is a decrease in β-catenin and pGSK-3β-ser(9) in the PFC and hippocampus of teenage suicide victims does indicate a disturbance in the Wnt signalling pathway in teenage suicide.

  18. Brain-derived neurotrophic factor signaling plays a role in resilience to stress promoted by isoquinoline in defeated mice.

    Science.gov (United States)

    Pesarico, Ana Paula; Rosa, Suzan G; Martini, Franciele; Goulart, Tales A; Zeni, Gilson; Nogueira, Cristina Wayne

    2017-11-01

    Certain stressful life events have been associated with the onset of depression. This study aims to investigate if 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI) is effective against social avoidance induced by social defeat stress model in mice. Furthermore, it was investigated the effects of FDPI in the mouse prefrontal cortical plasticity-related proteins and some parameters of toxicity. Adult Swiss mice were subjected to social defeat stress for 10 days. Two protocols with FDPI were carried out: 1- FDPI (25 mg/kg, intragastric) was administered to mice 24 h after the last social defeat stress episode; 2- FDPI (1-25 mg/kg, intragastric) was administered to mice once a day for 10 days concomitant with the social defeat stress. The mice performed social avoidance and locomotor tests. The prefrontal cortical protein contents of kinase B (Akt), extracellular signal-regulated kinase (ERK), cAMP-response element binding protein (CREB), pro-brain-derived neurotrophic factor (proBDNF), p75NTR, neuronal nuclear protein (NeuN) and nuclear factor-κB (NF-κB) were determined in mice. A single administration of FDPI (25 mg/kg) partially protected against social avoidance induced by stress in mice. Repeated administration of FDPI (25 mg/kg) protected against social avoidance induced by stress in mice. Social defeat stress decreased the protein contents of p75NTR, NeuN and the pERK/ERK ratio but increased those of proBDNF and the pCREB/CREB ratio, without changing that of NF-κB. Repeated administration of FDPI modulated signaling pathways altered by social defeat stress in mice. The present findings demonstrate that FDPI promoted resilience to stress in mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Brain pyroglutamate amyloid-β is produced by cathepsin B and is reduced by the cysteine protease inhibitor E64d, representing a potential Alzheimer's disease therapeutic.

    Science.gov (United States)

    Hook, Gregory; Yu, Jin; Toneff, Thomas; Kindy, Mark; Hook, Vivian

    2014-01-01

    Pyroglutamate amyloid-β peptides (pGlu-Aβ) are particularly pernicious forms of amyloid-β peptides (Aβ) present in Alzheimer's disease (AD) brains. pGlu-Aβ peptides are N-terminally truncated forms of full-length Aβ peptides (flAβ(1-40/42)) in which the N-terminal glutamate is cyclized to pyroglutamate to generate pGlu-Aβ(3-40/42). β-secretase cleavage of amyloid-β precursor protein (AβPP) produces flAβ(1-40/42), but it is not yet known whether the β-secretase BACE1 or the alternative β-secretase cathepsin B (CatB) participate in the production of pGlu-Aβ. Therefore, this study examined the effects of gene knockout of these proteases on brain pGlu-Aβ levels in transgenic AβPPLon mice, which express AβPP isoform 695 and have the wild-type (wt) β-secretase activity found in most AD patients. Knockout or overexpression of the CatB gene reduced or increased, respectively, pGlu-Aβ(3-40/42), flAβ(1-40/42), and pGlu-Aβ plaque load, but knockout of the BACE1 gene had no effect on those parameters in the transgenic mice. Treatment of AβPPLon mice with E64d, a cysteine protease inhibitor of CatB, also reduced brain pGlu-Aβ(3-42), flAβ(1-40/42), and pGlu-Aβ plaque load. Treatment of neuronal-like chromaffin cells with CA074Me, an inhibitor of CatB, resulted in reduced levels of pGlu-Aβ(3-40) released from the activity-dependent, regulated secretory pathway. Moreover, CatB knockout and E64d treatment has been previously shown to improve memory deficits in the AβPPLon mice. These data illustrate the role of CatB in producing pGlu-Aβ and flAβ that participate as key factors in the development of AD. The advantages of CatB inhibitors, especially E64d and its derivatives, as alternatives to BACE1 inhibitors in treating AD patients are discussed.

  20. Simple and cost-effective hardware and software for functional brain mapping using intrinsic optical signal imaging.

    Science.gov (United States)

    Harrison, Thomas C; Sigler, Albrecht; Murphy, Timothy H

    2009-09-15

    We describe a simple and low-cost system for intrinsic optical signal (IOS) imaging using stable LED light sources, basic microscopes, and commonly available CCD cameras. IOS imaging measures activity-dependent changes in the light reflectance of brain tissue, and can be performed with a minimum of specialized equipment. Our system uses LED ring lights that can be mounted on standard microscope objectives or video lenses to provide a homogeneous and stable light source, with less than 0.003% fluctuation across images averaged from 40 trials. We describe the equipment and surgical techniques necessary for both acute and chronic mouse preparations, and provide software that can create maps of sensory representations from images captured by inexpensive 8-bit cameras or by 12-bit cameras. The IOS imaging system can be adapted to commercial upright microscopes or custom macroscopes, eliminating the need for dedicated equipment or complex optical paths. This method can be combined with parallel high resolution imaging techniques such as two-photon microscopy.

  1. Community representatives: representing the "community"?

    Science.gov (United States)

    Jewkes, R; Murcott, A

    1998-04-01

    This paper takes as its starting point the apparent disjunction between the assumptions of the self-evidence of the meaning of community in major international declarations and strategies which promote community participation and the observation that meanings of "community" are a subject of extensive debate in literatures of social analysis and to some extent health. Given that the word's meaning is not agreed, those working to promote "community participation" in health are forced to adjudicate on competing meanings in order to operationalise the notion. This raises questions about how this is done and what are the implications of particular choices for what may be achieved by the participating "community". This paper presents the findings of an empirical study which examined the manner in which ideas of "community" are operationalised by people engaged in encouraging community participation in health promotion in the context of the selection of members for health for all steering groups in healthy cities projects in the United Kingdom. It argues that the demands of the role of the "community representative" are such that particular interpretations of "community" achieve ascendance. The paper explores the consequences of the interpretation of "community" as part of the "voluntary sector" and argues that this may compromise one of the stated desired outcomes of community participation i.e. extending democracy in health decision-making.

  2. Naringin Improves Neuronal Insulin Signaling, Brain Mitochondrial Function, and Cognitive Function in High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    Wang, Dongmei; Yan, Junqiang; Chen, Jing; Wu, Wenlan; Zhu, Xiaoying; Wang, Yong

    2015-10-01

    The epidemic and experimental studies have confirmed that the obesity induced by high-fat diet not only caused neuronal insulin resistance, but also induced brain mitochondrial dysfunction as well as learning impairment in mice. Naringin has been reported to posses biological functions which are beneficial to human cognitions, but its protective effects on HFD-induced cognitive deficits and underlying mechanisms have not been well characterized. In the present study Male C57BL/6 J mice were fed either a control or high-fat diet for 20 weeks and then randomized into four groups treated with their respective diets including control diet, control diet + naringin, high-fat diet (HFD), and high-fat diet + naringin (HFDN). The behavioral performance was assessed by using novel object recognition test and Morris water maze test. Hippocampal mitochondrial parameters were analyzed. Then the protein levels of insulin signaling pathway and the AMP-activated protein kinase (AMPK) in the hippocampus were detected by Western blot method. Our results showed that oral administration of naringin significantly improved the learning and memory abilities as evidenced by increasing recognition index by 52.5% in the novel object recognition test and inducing a 1.05-fold increase in the crossing-target number in the probe test, and ameliorated mitochondrial dysfunction in mice caused by HFD consumption. Moreover, naringin significantly enhanced insulin signaling pathway as indicated by a 34.5% increase in the expression levels of IRS-1, a 47.8% decrease in the p-IRS-1, a 1.43-fold increase in the p-Akt, and a 1.89-fold increase in the p-GSK-3β in the hippocampus of the HFDN mice versus HFD mice. Furthermore, the AMPK activity significantly increased in the naringin-treated (100 mg kg(-1) d(-1)) group. These findings suggest that an enhancement in insulin signaling and a decrease in mitochondrial dysfunction through the activation of AMPK may be one of the mechanisms that naringin

  3. Salidroside improves behavioral and histological outcomes and reduces apoptosis via PI3K/Akt signaling after experimental traumatic brain injury.

    Science.gov (United States)

    Chen, Szu-Fu; Tsai, Hsin-Ju; Hung, Tai-Ho; Chen, Chien-Cheng; Lee, Chao Yu; Wu, Chun-Hu; Wang, Pei-Yi; Liao, Nien-Chieh

    2012-01-01

    Traumatic brain injury (TBI) induces a complex sequence of apopototic cascades that contribute to secondary tissue damage. The aim of this study was to investigate the effects of salidroside, a phenolic glycoside with potent anti-apoptotic properties, on behavioral and histological outcomes, brain edema, and apoptosis following experimental TBI and the possible involvement of the phosphoinositide 3-kinase/protein kinase B (PI3K)/Akt signaling pathway. Mice subjected to controlled cortical impact injury received intraperitoneal salidroside (20, or 50 mg/kg) or vehicle injection 10 min after injury. Behavioral studies, histology analysis and brain water content assessment were performed. Levels of PI3K/Akt signaling-related molecules, apoptosis-related proteins, cytochrome C (CytoC), and Smac/DIABLO were also analyzed. LY294002, a PI3K inhibitor, was administered to examine the mechanism of protection. The protective effect of salidroside was also investigated in primary cultured neurons subjected to stretch injury. Treatment with 20 mg/kg salidroside significantly improved functional recovery and reduced brain tissue damage up to post-injury day 28. Salidroside also significantly reduced neuronal death, apoptosis, and brain edema at day 1. These changes were associated with significant decreases in cleaved caspase-3, CytoC, and Smac/DIABLO at days 1 and 3. Salidroside increased phosphorylation of Akt on Ser473 and the mitochondrial Bcl-2/Bax ratio at day 1, and enhanced phosphorylation of Akt on Thr308 at day 3. This beneficial effect was abolished by pre-injection of LY294002. Moreover, delayed administration of salidroside at 3 or 6 h post-injury reduced neuronal damage at day 1. Salidroside treatment also decreased neuronal vulnerability to stretch-induced injury in vitro. Post-injury salidroside improved long-term behavioral and histological outcomes and reduced brain edema and apoptosis following TBI, at least partially via the PI3K/Akt signaling pathway.

  4. Salidroside improves behavioral and histological outcomes and reduces apoptosis via PI3K/Akt signaling after experimental traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Szu-Fu Chen

    Full Text Available Traumatic brain injury (TBI induces a complex sequence of apopototic cascades that contribute to secondary tissue damage. The aim of this study was to investigate the effects of salidroside, a phenolic glycoside with potent anti-apoptotic properties, on behavioral and histological outcomes, brain edema, and apoptosis following experimental TBI and the possible involvement of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt signaling pathway.Mice subjected to controlled cortical impact injury received intraperitoneal salidroside (20, or 50 mg/kg or vehicle injection 10 min after injury. Behavioral studies, histology analysis and brain water content assessment were performed. Levels of PI3K/Akt signaling-related molecules, apoptosis-related proteins, cytochrome C (CytoC, and Smac/DIABLO were also analyzed. LY294002, a PI3K inhibitor, was administered to examine the mechanism of protection. The protective effect of salidroside was also investigated in primary cultured neurons subjected to stretch injury. Treatment with 20 mg/kg salidroside significantly improved functional recovery and reduced brain tissue damage up to post-injury day 28. Salidroside also significantly reduced neuronal death, apoptosis, and brain edema at day 1. These changes were associated with significant decreases in cleaved caspase-3, CytoC, and Smac/DIABLO at days 1 and 3. Salidroside increased phosphorylation of Akt on Ser473 and the mitochondrial Bcl-2/Bax ratio at day 1, and enhanced phosphorylation of Akt on Thr308 at day 3. This beneficial effect was abolished by pre-injection of LY294002. Moreover, delayed administration of salidroside at 3 or 6 h post-injury reduced neuronal damage at day 1. Salidroside treatment also decreased neuronal vulnerability to stretch-induced injury in vitro.Post-injury salidroside improved long-term behavioral and histological outcomes and reduced brain edema and apoptosis following TBI, at least partially via the PI3K/Akt signaling

  5. Investigation of Resonance Effect Caused by Local Exposure of Extremely Low Frequency Magnetic Field on Brain Signals: A Randomize Clinical Trial

    Directory of Open Access Journals (Sweden)

    Rasul Zadeh Tabataba’ei K

    2011-03-01

    Full Text Available Background and Objectives: Some studies have investigated the effects of extremely low frequency magnetic fields (ELF-MFs on brain signals, but only few of them have reported that humans exposed to magnetic fields exhibit changes in brain signals at the frequency of stimulation, i.e. resonance effect. In most investigations, researchers usually take advantage of a uniform field which encompasses the head. The aim of present study was to expose different parts of the brain to ELF-MFs locally and to investigate variation of brain signal and resonance effect.Methods: The subjects consisting of 19 male-students with the mean age of 25.6±1.6 years participated in this study. Local ELF-MFs with 3, 5, 10, 17 and 45Hz frequencies and 240 μT intensity was applied on five points (T3, T4, Cz, F3 and F4 of participants scalp Separately in 10-20 system. In the end, relative power over this points in common frequency bands and at the frequency of magnetic fields was evaluated by paired t-test.Results: Exposure of Central area by local magnetic field caused significant change (p<0.05 in the forehead alpha band. Reduction in the alpha band over central area was observed when temporal area was exposed to ELF MF.Conclusion: The results showed that resonance effect in the brain signals caused by local magnetic field exposure was not observed and change in every part of the relative power spectrum might occur. The changes in the EEG bands were not limited necessarily to the exposure point.

  6. Heme oxygenase-1 plays a pro-life role in experimental brain stem death via nitric oxide synthase I/protein kinase G signaling at rostral ventrolateral medulla

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    Dai Kuang-Yu

    2010-09-01

    Full Text Available Abstract Background Despite its clinical importance, a dearth of information exists on the cellular and molecular mechanisms that underpin brain stem death. A suitable neural substrate for mechanistic delineation on brain stem death resides in the rostral ventrolateral medulla (RVLM because it is the origin of a life-and-death signal that sequentially increases (pro-life and decreases (pro-death to reflect the advancing central cardiovascular regulatory dysfunction during the progression towards brain stem death in critically ill patients. The present study evaluated the hypothesis that heme oxygnase-1 (HO-1 may play a pro-life role as an interposing signal between hypoxia-inducible factor-1 (HIF-1 and nitric oxide synthase I (NOS I/protein kinase G (PKG cascade in RVLM, which sustains central cardiovascular regulatory functions during brain stem death. Methods We performed cardiovascular, pharmacological, biochemical and confocal microscopy experiments in conjunction with an experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos (Mev; 10 nmol bilaterally into RVLM of adult male Sprague-Dawley rats. Results Western blot analysis coupled with laser scanning confocal microscopy revealed that augmented HO-1 expression that was confined to the cytoplasm of RVLM neurons occurred preferentially during the pro-life phase of experimental brain stem death and was antagonized by immunoneutralization of HIF-1α or HIF-1β in RVLM. On the other hand, the cytoplasmic presence of HO-2 in RVLM neurons manifested insignificant changes during both phases. Furthermore, immunoneutralization of HO-1 or knockdown of ho-1 gene in RVLM blunted the augmented life-and-death signals exhibited during the pro-life phase. Those pretreatments also blocked the upregulated pro-life NOS I/PKG signaling without affecting the pro-death NOS II/peroxynitrite cascade in RVLM. Conclusions We conclude that transcriptional

  7. In vivo optical microprobe imaging for intracellular Ca2+ dynamics in response to dopaminergic signaling in deep brain evoked by cocaine

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    Luo, Zhongchi; Pan, Yingtian; Du, Congwu

    2012-02-01

    Ca2+ plays a vital role as second messenger in signal transduction and the intracellular Ca2+ ([Ca2+]i) change is an important indicator of neuronal activity in the brain, including both cortical and subcortical brain regions. Due to the highly scattering and absorption of brain tissue, it is challenging to optically access the deep brain regions (e.g., striatum at >3mm under the brain surface) and image [Ca2+]i changes with cellular resolutions. Here, we present two micro-probe approaches (i.e., microlens, and micro-prism) integrated with a fluorescence microscope modified to permit imaging of neuronal [Ca2+]i signaling in the striatum using a calcium indicator Rhod2(AM). While a micro-prism probe provides a larger field of view to image neuronal network from cortex to striatum, a microlens probe enables us to track [Ca2+]i dynamic change in individual neurons within the brain. Both techniques are validated by imaging neuronal [Ca2+]i changes in transgenic mice with dopamine receptors (D1R, D2R) expressing EGFP. Our results show that micro-prism images can map the distribution of D1R- and D2R-expressing neurons in various brain regions and characterize their different mean [Ca2+]i changes induced by an intervention (e.g., cocaine administration, 8mg/kg., i.p). In addition, microlens images can characterize the different [Ca2+]i dynamics of D1 and D2 neurons in response to cocaine, including new mechanisms of these two types of neurons in striatum. These findings highlight the power of the optical micro-probe imaging for dissecting the complex cellular and molecular insights of cocaine in vivo.

  8. A clinico-radiological study on 254 cases of pontine high signals on magnetic resonance imaging in relation to brain stem semiology

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    Watanabe, Masaki; Takahashi, Akira (Nagoya Univ. (Japan). Faculty of Medicine); Arahata, Yutaka; Motegi, Yoshimasa; Furuse, Masahiro

    1993-11-01

    A total of 254 patients who were proved to have pontine high intensity areas on T[sub 2]-weighted magnetic resonance imaging (MRI) were analyzed in relation to brain stem semiology. A comparative study on MRI and MR angiography was made between 254 patients with pontine high signals and 276 control cases showing no abnormality either on T[sub 1] or T[sub 2]-weighted images. Of the 254 patients, 62 had transient subjective complaints such as vertigo-dizziness. Supratentorial high signals, basilar artery tortuousness and vertebral artery asymmetry on MR angiography were seen more frequently in patients with pontine high signals than in the controls. In conclusion, pontine high signals may result from diffuse arteriosclerosis and MR angiography is considered to be a useful screening method. (author).

  9. Activation of brain-derived neurotrophic factor/tropomyosin-related kinase B signaling accompanying filial imprinting in domestic chicks (Gallus gallus domesticus).

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    Yamaguchi, Shinji; Aoki, Naoya; Kobayashi, Daisuke; Kitajima, Takaaki; Iikubo, Eiji; Katagiri, Sachiko; Matsushima, Toshiya; Homma, Koichi J

    2011-12-07

    Newly hatched domestic chicks serve as an important model for experimental studies of neural and behavioral plasticity. Brain-derived neurotrophic factor (BDNF) has been shown to play a critical role in synaptic plasticity, including long-term potentiation, which underlies learning and memory in rodents. Here we show that BDNF mRNA levels increased in the intermediate medial hyperpallium apicale (IMHA), which is the caudal area of the visual Wulst, of imprinted chick brains, and the upregulation of gene expression correlated with the strength of the learned preference to the training object. In addition, activation of tropomyosin-related kinase B (TrkB)/phosphatidylinositol 3-kinase signaling was associated with filial imprinting. However, pharmacological deprivation of TrkB phosphorylation in IMHA did not impair memory formation, suggesting that activation of BDNF/TrkB signaling in IMHA is not involved in memory acquisition in filial imprinting.

  10. Inhibition of type I insulin-like growth factor receptor signaling attenuates the development of breast cancer brain metastasis.

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    Saldana, Sandra M; Lee, Heng-Huan; Lowery, Frank J; Khotskaya, Yekaterina B; Xia, Weiya; Zhang, Chenyu; Chang, Shih-Shin; Chou, Chao-Kai; Steeg, Patricia S; Yu, Dihua; Hung, Mien-Chie

    2013-01-01

    Brain metastasis is a common cause of mortality in cancer patients, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF-IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that IGF-IR is constitutively autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR results in a decrease of phospho-AKT and phospho-p70s6k, as well as decreased migration and invasion of MDA-MB-231Br brain-seeking cells. In addition, transient ablation of IGFBP3, which is overexpressed in brain-seeking cells, blocks IGF-IR activation. Using an in vivo experimental brain metastasis model, we show that IGF-IR knockdown brain-seeking cells have reduced potential to establish brain metastases. Finally, we demonstrate that the malignancy of brain-seeking cells is attenuated by pharmacological inhibition with picropodophyllin, an IGF-IR-specific tyrosine kinase inhibitor. Together, our data suggest that the IGF-IR is an important mediator of brain metastasis and its ablation delays the onset of brain metastases in our model system.

  11. Signal-independent noise in intracortical brain-computer interfaces causes movement time properties inconsistent with Fitts’ law

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    Willett, Francis R.; Murphy, Brian A.; Memberg, William D.; Blabe, Christine H.; Pandarinath, Chethan; Walter, Benjamin L.; Sweet, Jennifer A.; Miller, Jonathan P.; Henderson, Jaimie M.; Shenoy, Krishna V.; Hochberg, Leigh R.; Kirsch, Robert F.; Bolu Ajiboye, A.

    2017-04-01

    Objective. Do movements made with an intracortical BCI (iBCI) have the same movement time properties as able-bodied movements? Able-bodied movement times typically obey Fitts’ law: \\text{MT}=a+b{{log}2}(D/R) (where MT is movement time, D is target distance, R is target radius, and a,~b are parameters). Fitts’ law expresses two properties of natural movement that would be ideal for iBCIs to restore: (1) that movement times are insensitive to the absolute scale of the task (since movement time depends only on the ratio D/R ) and (2) that movements have a large dynamic range of accuracy (since movement time is logarithmically proportional to D/R ). Approach. Two participants in the BrainGate2 pilot clinical trial made cortically controlled cursor movements with a linear velocity decoder and acquired targets by dwelling on them. We investigated whether the movement times were well described by Fitts’ law. Main results. We found that movement times were better described by the equation \\text{MT}=a+bD+c{{R}-2} , which captures how movement time increases sharply as the target radius becomes smaller, independently of distance. In contrast to able-bodied movements, the iBCI movements we studied had a low dynamic range of accuracy (absence of logarithmic proportionality) and were sensitive to the absolute scale of the task (small targets had long movement times regardless of the D/R ratio). We argue that this relationship emerges due to noise in the decoder output whose magnitude is largely independent of the user’s motor command (signal-independent noise). Signal-independent noise creates a baseline level of variability that cannot be decreased by trying to move slowly or hold still, making targets below a certain size very hard to acquire with a standard decoder. Significance. The results give new insight into how iBCI movements currently differ from able-bodied movements and suggest that restoring a Fitts’ law-like relationship to iBCI movements may require

  12. Signal-independent noise in intracortical brain-computer interfaces causes movement time properties inconsistent with Fitts' law.

    Science.gov (United States)

    Willett, Francis R; Murphy, Brian A; Memberg, William D; Blabe, Christine H; Pandarinath, Chethan; Walter, Benjamin L; Sweet, Jennifer A; Miller, Jonathan P; Henderson, Jaimie M; Shenoy, Krishna V; Hochberg, Leigh R; Kirsch, Robert F; Ajiboye, A Bolu

    2017-04-01

    Do movements made with an intracortical BCI (iBCI) have the same movement time properties as able-bodied movements? Able-bodied movement times typically obey Fitts' law: [Formula: see text] (where MT is movement time, D is target distance, R is target radius, and [Formula: see text] are parameters). Fitts' law expresses two properties of natural movement that would be ideal for iBCIs to restore: (1) that movement times are insensitive to the absolute scale of the task (since movement time depends only on the ratio [Formula: see text]) and (2) that movements have a large dynamic range of accuracy (since movement time is logarithmically proportional to [Formula: see text]). Two participants in the BrainGate2 pilot clinical trial made cortically controlled cursor movements with a linear velocity decoder and acquired targets by dwelling on them. We investigated whether the movement times were well described by Fitts' law. We found that movement times were better described by the equation [Formula: see text], which captures how movement time increases sharply as the target radius becomes smaller, independently of distance. In contrast to able-bodied movements, the iBCI movements we studied had a low dynamic range of accuracy (absence of logarithmic proportionality) and were sensitive to the absolute scale of the task (small targets had long movement times regardless of the [Formula: see text] ratio). We argue that this relationship emerges due to noise in the decoder output whose magnitude is largely independent of the user's motor command (signal-independent noise). Signal-independent noise creates a baseline level of variability that cannot be decreased by trying to move slowly or hold still, making targets below a certain size very hard to acquire with a standard decoder. The results give new insight into how iBCI movements currently differ from able-bodied movements and suggest that restoring a Fitts' law-like relationship to iBCI movements may require non

  13. IL-1β Induces MMP-9-Dependent Brain Astrocytic Migration via Transactivation of PDGF Receptor/NADPH Oxidase 2-Derived Reactive Oxygen Species Signals.

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    Yang, Chuen-Mao; Hsieh, Hsi-Lung; Yu, Ping-Hsien; Lin, Chih-Chung; Liu, Shiau-Wen

    2015-08-01

    Matrix metalloproteinase-9 (MMP-9) plays a crucial role in pathological processes of brain inflammation, injury, and neurodegeneration. Moreover, cytokines such as interleukin-1β (IL-1β) induce expression of several inflammatory mediators in brain astrocytes, which may be important for brain inflammatory disorders. Recent studies have implicated that increased oxidative stress may contribute to the brain injury and inflammation. However, whether IL-1β-induced MMP-9 expression mediated through oxidative stress remains unclear. Therefore, we investigated the role of redox signals in IL-1β-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells). Herein, we first demonstrated that reactive oxygen species (ROS) play a crucial role in ILβ-induced MMP-9 expression by zymography, real-time PCR, and ROS staining in cultured RBA-1 cells. Next, IL-1β-induced MMP-9 expression is mediated through a c-Src-mediated transactivation of PDGFR/PI3K/Akt cascade linking to p47(phox)/NADPH oxidase 2 (Nox2)/ROS signaling pathway. Nox2-dependent ROS generation led to activation of MAPKs and the downstream transcription factors NF-κB and AP-1 (i.e., ATF2), which enhanced MMP-9 promoter activity, and thereby turned on transcription of MMP-9 gene. Functionally, IL-1β-induced MMP-9 expression promoted astrocytic migration. These results demonstrated that in RBA-1 cells, activation of NF-κB and AP-1 (ATF2) by the c-Src/PDGFR/PI3K/Akt-mediated Nox2/ROS/MAPKs signals is required for upregulation of MMP-9 and cell migration enhanced by IL-1β.

  14. The Whole-Brain “Global” Signal from Resting State fMRI as a Potential Biomarker of Quantitative State Changes in Glucose Metabolism

    Science.gov (United States)

    Thompson, Garth J.; Grimmer, Timo; Drzezga, Alexander; Herman, Peter

    2016-01-01

    Abstract The evolution of functional magnetic resonance imaging to resting state (R-fMRI) allows measurement of changes in brain networks attributed to state changes, such as in neuropsychiatric diseases versus healthy controls. Since these networks are observed by comparing normalized R-fMRI signals, it is difficult to determine the metabolic basis of such group differences. To investigate the metabolic basis of R-fMRI network differences within a normal range, eyes open versus eyes closed in healthy human subjects was used. R-fMRI was recorded simultaneously with fluoro-deoxyglucose positron emission tomography (FDG-PET). Higher baseline FDG was observed in the eyes open state. Variance-based metrics calculated from R-fMRI did not match the baseline shift in FDG. Functional connectivity density (FCD)-based metrics showed a shift similar to the baseline shift of FDG, however, this was lost if R-fMRI “nuisance signals” were regressed before FCD calculation. Average correlation with the mean R-fMRI signal across the whole brain, generally regarded as a “nuisance signal,” also showed a shift similar to the baseline of FDG. Thus, despite lacking a baseline itself, changes in whole-brain correlation may reflect changes in baseline brain metabolism. Conversely, variance-based metrics may remain similar between states due to inherent region-to-region differences overwhelming the differences between normal physiological states. As most previous studies have excluded the spatial means of R-fMRI metrics from their analysis, this work presents the first evidence of a potential R-fMRI biomarker for baseline shifts in quantifiable metabolism between brain states. PMID:27029438

  15. G-CSF protects human brain vascular endothelial cells injury induced by high glucose, free fatty acids and hypoxia through MAPK and Akt signaling.

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    Jingjing Su

    Full Text Available Granulocyte-colony stimulating factor (G-CSF has been shown to play a neuroprotective role in ischemic stroke by mobilizing bone marrow (BM-derived endothelial progenitor cells (EPCs, promoting angiogenesis, and inhibiting apoptosis. Impairments in mobilization and function of the BM-derived EPCs have previously been reported in animal and human studies of diabetes where there is both reduction in the levels of the BM-derived EPCs and its ability to promote angiogenesis. This is hypothesized to account for the pathogenesis of diabetic vascular complications such as stroke. Here, we sought to investigate the effects of G-CSF on diabetes-associated cerebral vascular defect. We observed that pretreatment of the cultured human brain vascular endothelial cells (HBVECs with G-CSF largely prevented cell death induced by the combination stimulus with high glucose, free fatty acids (FFA and hypoxia by increasing cell viability, decreasing apoptosis and caspase-3 activity. Cell ultrastructure measured by transmission electron microscope (TEM revealed that G-CSF treatment nicely reduced combination stimulus-induced cell apoptosis. The results from fluorescent probe Fluo-3/AM showed that G-CSF greatly suppressed the levels of intracellular calcium ions under combination stimulus. We also found that G-CSF enhanced the expression of cell cycle proteins such as human cell division cycle protein 14A (hCdc14A, cyclinB and cyclinE, inhibited p53 activity, and facilitated cell cycle progression following combination stimulus. In addition, activation of extracellular signal-regulated kinase1/2 (ERK1/2 and Akt, and deactivation of c-Jun N terminal kinase (JNK and p38 were proved to be required for the pro-survival effects of G-CSF on HBVECs exposed to combination stimulus. Overall, G-CSF is capable of alleviating HBVECs injury triggered by the combination administration with high glucose, FFA and hypoxia involving the mitogen-activated protein kinases (MAPK and Akt

  16. Expression of reelin, its receptors and its intracellular signaling protein, Disabled1 in the canary brain: relationships with the song control system.

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    Balthazart, J; Voigt, C; Boseret, G; Ball, G F

    2008-06-02

    Songbirds produce learned vocalizations that are controlled by a specialized network of neural structures, the song control system. Several nuclei in this song control system demonstrate a marked degree of adult seasonal plasticity. Nucleus volume varies seasonally based on changes in cell size or spacing, and in the case of nucleus HVC and area X on the incorporation of new neurons. Reelin, a large glycoprotein defective in reeler mice, is assumed to determine the final location of migrating neurons in the developing brain. In mammals, reelin is also expressed in the adult brain but its functions are less well characterized. We investigated the relationships between the expression of reelin and/or its receptors and the dramatic seasonal plasticity in the canary (Serinus canaria) brain. We detected a broad distribution of the reelin protein, its mRNA and the mRNAs encoding for the reelin receptors (VLDLR and ApoER2) as well as for its intracellular signaling protein, Disabled1. These different mRNAs and proteins did not display the same neuroanatomical distribution and were not clearly associated, in an exclusive manner, with telencephalic brain areas that incorporate new neurons in adulthood. Song control nuclei were associated with a particular specialized expression of reelin and its mRNA, with the reelin signal being either denser or lighter in the song nucleus than in the surrounding tissue. The density of reelin-immunoreactive structures did not seem to be affected by 4 weeks of treatment with exogenous testosterone. These observations do not provide conclusive evidence that reelin plays a prominent role in the positioning of new neurons in the adult canary brain but call for additional work on this protein analyzing its expression comparatively during development and in adulthood with a better temporal resolution at critical points in the reproductive cycle when brain plasticity is known to occur.

  17. Wogonin improves histological and functional outcomes, and reduces activation of TLR4/NF-κB signaling after experimental traumatic brain injury.

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    Chien-Cheng Chen

    Full Text Available Traumatic brain injury (TBI initiates a neuroinflammatory cascade that contributes to neuronal damage and behavioral impairment. This study was undertaken to investigate the effects of wogonin, a flavonoid with potent anti-inflammatory properties, on functional and histological outcomes, brain edema, and toll-like receptor 4 (TLR4- and nuclear factor kappa B (NF-κB-related signaling pathways in mice following TBI.Mice subjected to controlled cortical impact injury were injected with wogonin (20, 40, or 50 mg·kg(-1 or vehicle 10 min after injury. Behavioral studies, histology analysis, and measurement of blood-brain barrier (BBB permeability and brain water content were carried out to assess the effects of wogonin. Levels of TLR4/NF-κB-related inflammatory mediators were also examined. Treatment with 40 mg·kg(-1 wogonin significantly improved functional recovery and reduced contusion volumes up to post-injury day 28. Wogonin also significantly reduced neuronal death, BBB permeability, and brain edema beginning at day 1. These changes were associated with a marked reduction in leukocyte infiltration, microglial activation, TLR4 expression, NF-κB translocation to nucleus and its DNA binding activity, matrix metalloproteinase-9 activity, and expression of inflammatory mediators, including interleukin-1β, interleukin-6, macrophage inflammatory protein-2, and cyclooxygenase-2.Our results show that post-injury wogonin treatment improved long-term functional and histological outcomes, reduced brain edema, and attenuated the TLR4/NF-κB-mediated inflammatory response in mouse TBI. The neuroprotective effects of wogonin may be related to modulation of the TLR4/NF-κB signaling pathway.

  18. Wnt3a upregulates brain-derived insulin by increasing NeuroD1 via Wnt/β-catenin signaling in the hypothalamus.

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    Lee, Jaemeun; Kim, Kyungchan; Yu, Seong-Woon; Kim, Eun-Kyoung

    2016-03-08

    Insulin plays diverse roles in the brain. Although insulin produced by pancreatic β-cells that crosses the blood-brain barrier is a major source of brain insulin, recent studies suggest that insulin is also produced locally within the brain. However, the mechanisms underlying the production of brain-derived insulin (BDI) are not yet known. Here, we examined the effect of Wnt3a on BDI production in a hypothalamic cell line and hypothalamic tissue. In N39 hypothalamic cells, Wnt3a treatment significantly increased the expression of the Ins2 gene, which encodes the insulin isoform predominant in the mouse brain, by activating Wnt/β-catenin signaling. The concentration of insulin was higher in culture medium of Wnt3a-treated cells than in that of untreated cells. Interestingly, neurogenic differentiation 1 (NeuroD1), a target of Wnt/β-catenin signaling and one of transcription factors for insulin, was also induced by Wnt3a treatment in a time- and dose-dependent manner. In addition, the treatment of BIO, a GSK3 inhibitor, also increased the expression of Ins2 and NeuroD1. Knockdown of NeuroD1 by lentiviral shRNAs reduced the basal expression of Ins2 and suppressed Wnt3a-induced Ins2 expression. To confirm the Wnt3a-induced increase in Ins2 expression in vivo, Wnt3a was injected into the hypothalamus of mice. Wnt3a increased the expression of NeuroD1 and Ins2 in the hypothalamus in a manner similar to that observed in vitro. Taken together, these results suggest that BDI production is regulated by the Wnt/β-catenin/NeuroD1 pathway in the hypothalamus. Our findings will help to unravel the regulation of BDI production in the hypothalamus.

  19. A System for True and False Memory Prediction Based on 2D and 3D Educational Contents and EEG Brain Signals

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    Saeed Bamatraf

    2016-01-01

    Full Text Available We studied the impact of 2D and 3D educational contents on learning and memory recall using electroencephalography (EEG brain signals. For this purpose, we adopted a classification approach that predicts true and false memories in case of both short term memory (STM and long term memory (LTM and helps to decide whether there is a difference between the impact of 2D and 3D educational contents. In this approach, EEG brain signals are converted into topomaps and then discriminative features are extracted from them and finally support vector machine (SVM which is employed to predict brain states. For data collection, half of sixty-eight healthy individuals watched the learning material in 2D format whereas the rest watched the same material in 3D format. After learning task, memory recall tasks were performed after 30 minutes (STM and two months (LTM, and EEG signals were recorded. In case of STM, 97.5% prediction accuracy was achieved for 3D and 96.6% for 2D and, in case of LTM, it was 100% for both 2D and 3D. The statistical analysis of the results suggested that for learning and memory recall both 2D and 3D materials do not have much difference in case of STM and LTM.

  20. Reactive oxygen species alter brain endothelial tight junction dynamics via RhoA, PI3 kinase, and PKB signaling

    NARCIS (Netherlands)

    Schreibelt, Gerty; Kooij, Gijs; Reijerkerk, Arie; van Doorn, Ruben; Gringhuis, Sonja I.; van der Pol, Susanne; Weksler, Babette B.; Romero, Ignacio A.; Couraud, Pierre-Olivier; Piontek, Jörg; Blasig, Ingolf E.; Dijkstra, Christine D.; Ronken, Eric; de Vries, Helga E.

    2007-01-01

    The blood-brain barrier (BBB) prevents the entrance of circulating molecules and immune cells into the central nervous system. The barrier is formed by specialized brain endothelial cells that are interconnected by tight junctions (TJ). A defective function of the BBB has been described for a

  1. Reactive oxygen species alter brain endothelial tight junction dynamics via RhoA, PI3 kinase, and PKB signaling.

    NARCIS (Netherlands)

    Schreibelt, G.; Kooij, G.; Reijerkerk, A.; Doorn, R. van; Gringhuis, S.I.; Pol, S. van der; Weksler, B.B.; Romero, I.A.; Couraud, P.O.; Piontek, J.; Blasig, I.E.; Dijkstra, C.D.; Ronken, E.; Vries, H.E. de

    2007-01-01

    The blood-brain barrier (BBB) prevents the entrance of circulating molecules and immune cells into the central nervous system. The barrier is formed by specialized brain endothelial cells that are interconnected by tight junctions (TJ). A defective function of the BBB has been described for a

  2. Regulation of Monocarboxylic Acid Transporter 1 Trafficking by the Canonical Wnt/β-Catenin Pathway in Rat Brain Endothelial Cells Requires Cross-talk with Notch Signaling.

    Science.gov (United States)

    Liu, Zejian; Sneve, Mary; Haroldson, Thomas A; Smith, Jeffrey P; Drewes, Lester R

    2016-04-08

    The transport of monocarboxylate fuels such as lactate, pyruvate, and ketone bodies across brain endothelial cells is mediated by monocarboxylic acid transporter 1 (MCT1). Although the canonical Wnt/β-catenin pathway is required for rodent blood-brain barrier development and for the expression of associated nutrient transporters, the role of this pathway in the regulation of brain endothelial MCT1 is unknown. Here we report expression of nine members of the frizzled receptor family by the RBE4 rat brain endothelial cell line. Furthermore, activation of the canonical Wnt/β-catenin pathway in RBE4 cells via nuclear β-catenin signaling with LiCl does not alter brain endothelialMct1mRNA but increases the amount of MCT1 transporter protein. Plasma membrane biotinylation studies and confocal microscopic examination of mCherry-tagged MCT1 indicate that increased transporter results from reduced MCT1 trafficking from the plasma membrane via the endosomal/lysosomal pathway and is facilitated by decreased MCT1 ubiquitination following LiCl treatment. Inhibition of the Notch pathway by the γ-secretase inhibitorN-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycinet-butyl ester negated the up-regulation of MCT1 by LiCl, demonstrating a cross-talk between the canonical Wnt/β-catenin and Notch pathways. Our results are important because they show, for the first time, the regulation of MCT1 in cerebrovascular endothelial cells by the multifunctional canonical Wnt/β-catenin and Notch signaling pathways. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Effects of treadmill exercise on brain insulin signaling and β-amyloid in intracerebroventricular streptozotocin induced-memory impairment in rats.

    Science.gov (United States)

    Kang, Eun Bum; Cho, Joon Yong

    2014-03-01

    The purpose of the study is to explore effect of 6 weeks treadmill exercise on brain insulin signaling and β-amyloid(Aβ). The rat model of Alzheimer's disease(AD) used in the present study was induced by the intracerebroventricular(ICV) streptozotocin(STZ). To produce the model of animal with AD, STZ(1.5mg/kg) was injected to a cerebral ventricle of both cerebrums of Sprague-Dawley rat(20 weeks). The experimental animals were divided into ICV-Sham(n=7), ICV-STZ CON(n=7), ICV-STZ EXE(n=7). Treadmill exercise was done for 30 min a day, 5 days a week for 6 weeks. Passive avoidance task was carried out before and after treadmill exercise. The results of this study show that treadmill exercise activated Protein kinase B(AKT)/ Glycogen synthase kinase 3α (GSK3α), possibly via activation of insulin receptor(IR) and insulin receptor substrate(IRS) and reduced Aβ in the brain of ICV-STZ rats. More interestingly, treadmill exercise improved cognitive function of ICV-STZ rats. Finally, physical exercise or physical activity gave positive influences on brain insulin signaling pathway. Therefore, treadmill exercise can be applied to improve AD as preventive and therapeutic method.

  4. Blood-brain barrier permeability imaging using perfusion computed tomography

    Directory of Open Access Journals (Sweden)

    Avsenik Jernej

    2015-06-01

    Full Text Available Background. The blood-brain barrier represents the selective diffusion barrier at the level of the cerebral microvascular endothelium. Other functions of blood-brain barrier include transport, signaling and osmoregulation. Endothelial cells interact with surrounding astrocytes, pericytes and neurons. These interactions are crucial to the development, structural integrity and function of the cerebral microvascular endothelium. Dysfunctional blood-brain barrier has been associated with pathologies such as acute stroke, tumors, inflammatory and neurodegenerative diseases.

  5. Shear Stress Induces Differentiation of Endothelial Lineage Cells to Protect Neonatal Brain from Hypoxic-Ischemic Injury through NRP1 and VEGFR2 Signaling

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    Chia-Wei Huang

    2015-01-01

    Full Text Available Neonatal hypoxic-ischemic (HI brain injuries disrupt the integrity of neurovascular structure and lead to lifelong neurological deficit. The devastating damage can be ameliorated by preserving the endothelial network, but the source for therapeutic cells is limited. We aim to evaluate the beneficial effect of mechanical shear stress in the differentiation of endothelial lineage cells (ELCs from adipose-derived stem cells (ASCs and the possible intracellular signals to protect HI injury using cell-based therapy in the neonatal rats. The ASCs expressed early endothelial markers after biochemical stimulation of endothelial growth medium. The ELCs with full endothelial characteristics were accomplished after a subsequential shear stress application for 24 hours. When comparing the therapeutic potential of ASCs and ELCs, the ELCs treatment significantly reduced the infarction area and preserved neurovascular architecture in HI injured brain. The transplanted ELCs can migrate and engraft into the brain tissue, especially in vessels, where they promoted the angiogenesis. The activation of Akt by neuropilin 1 (NRP1 and vascular endothelial growth factor receptor 2 (VEGFR2 was important for ELC migration and following in vivo therapeutic outcomes. Therefore, the current study demonstrated importance of mechanical factor in stem cell differentiation and showed promising protection of brain from HI injury using ELCs treatment.

  6. Effects of ketamine administration on mTOR and reticulum stress signaling pathways in the brain after the infusion of rapamycin into prefrontal cortex.

    Science.gov (United States)

    Abelaira, Helena M; Réus, Gislaine Z; Ignácio, Zuleide M; Dos Santos, Maria Augusta B; de Moura, Airam B; Matos, Danyela; Demo, Júlia P; da Silva, Júlia B I; Michels, Monique; Abatti, Mariane; Sonai, Beatriz; Dal Pizzol, Felipe; Carvalho, André F; Quevedo, João

    2017-04-01

    Recent studies show that activation of the mTOR signaling pathway is required for the rapid antidepressant actions of glutamate N-methyl-D-aspartate (NMDA) receptor antagonists. A relationship between mTOR kinase and the endoplasmic reticulum (ER) stress pathway, also known as the unfolded protein response (UPR) has been shown. We evaluate the effects of ketamine administration on the mTOR signaling pathway and proteins of UPR in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens, after the inhibiton of mTOR signaling in the PFC. Male adult Wistar rats received pharmacological mTOR inhibitor, rapamycin (0.2 nmol), or vehicle into the PFC and then a single dose of ketamine (15 mg/kg, i.p.). The immunocontent of mTOR, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), eukaryotic elongation factor 2 kinase (eEF2K) homologous protein (CHOP), PKR-like ER kinase (PERK) and inositol-requiring enzyme 1 (IRE1) - alpha were determined in the brain. The mTOR levels were reduced in the rapamycin group treated with saline and ketamine in the PFC; p4EBP1 levels were reduced in the rapamycin group treated with ketamine in the PFC and nucleus accumbens; the levels of peEF2K were increased in the PFC in the vehicle group treated with ketamine and reduced in the rapamycin group treated with ketamine. The PERK and IRE1-alpha levels were decreased in the PFC in the rapamycin group treated with ketamine. Our results suggest that mTOR signaling inhibition by rapamycin could be involved, at least in part, with the mechanism of action of ketamine; and the ketamine antidepressant on ER stress pathway could be also mediated by mTOR signaling pathway in certain brain structures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. The mitochondrial uncoupler DNP triggers brain cell mTOR signaling network reprogramming and CREB pathway up-regulation.

    Science.gov (United States)

    Liu, Dong; Zhang, Yongqing; Gharavi, Robert; Park, Hee Ra; Lee, Jaewon; Siddiqui, Sana; Telljohann, Richard; Nassar, Matthew R; Cutler, Roy G; Becker, Kevin G; Mattson, Mark P

    2015-08-01

    Mitochondrial metabolism is highly responsive to nutrient availability and ongoing activity in neuronal circuits. The molecular mechanisms by which brain cells respond to an increase in cellular energy expenditure are largely unknown. Mild mitochondrial uncoupling enhances cellular energy expenditure in mitochondria and can be induced with 2,4-dinitrophenol (DNP), a proton ionophore previously used for weight loss. We found that DNP treatment reduces mitochondrial membrane potential, increases intracellular Ca(2+) levels and reduces oxidative stress in cerebral cortical neurons. Gene expression profiling of the cerebral cortex of DNP-treated mice revealed reprogramming of signaling cascades that included suppression of the mammalian target of rapamycin (mTOR) and insulin--PI3K - MAPK pathways, and up-regulation of tuberous sclerosis complex 2, a negative regulator of mTOR. Genes encoding proteins involved in autophagy processes were up-regulated in response to DNP. CREB (cAMP-response element-binding protein) signaling, Arc and brain-derived neurotrophic factor, which play important roles in synaptic plasticity and adaptive cellular stress responses, were up-regulated in response to DNP, and DNP-treated mice exhibited improved performance in a test of learning and memory. Immunoblot analysis verified that key DNP-induced changes in gene expression resulted in corresponding changes at the protein level. Our findings suggest that mild mitochondrial uncoupling triggers an integrated signaling response in brain cells characterized by reprogramming of mTOR and insulin signaling, and up-regulation of pathways involved in adaptive stress responses, molecular waste disposal, and synaptic plasticity. Physiological bioenergetic challenges such as exercise and fasting can enhance neuroplasticity and protect neurons against injury and neurodegeneration. Here, we show that the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) elicits adaptive signaling responses in the

  8. Brain Basics

    Medline Plus

    Full Text Available ... Chemical signals from other cells guide neurons in forming various brain structures. Neighboring neurons make connections with ... our original set of DNA. Sometimes this copying process is imperfect, leading to a gene mutation that ...

  9. Brain Basics

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    Full Text Available ... and certain abilities, such as a good singing voice. A gene is a segment of DNA that ... as in areas of the brain that control movement. When electrical signals are abnormal, they can cause ...

  10. Brain Basics

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    Full Text Available ... illnesses, such as depression, can occur when this process does not work correctly. Communication between neurons can also be electrical, such as in areas of the brain that control movement. When electrical signals are abnormal, they can ...

  11. Brain Basics

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    Full Text Available ... another as chemical or electrical signals. The brain begins as a small group of cells in the ... how she's responding to the treatment. She also begins regular talk therapy sessions with her psychiatrist. In ...

  12. Brain Basics

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    Full Text Available ... Us Home About the Director Advisory Boards and Groups Strategic Plan Offices and Divisions Budget Careers at ... electrical signals. The brain begins as a small group of cells in the outer layer of a ...

  13. Brain Basics

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    Full Text Available ... and information that the cell needs for growth, metabolism, and repair. Cytoplasm is the substance that fills ... as in areas of the brain that control movement. When electrical signals are abnormal, they can cause ...

  14. Brain Basics

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    Full Text Available ... as in areas of the brain that control movement. When electrical signals are abnormal, they can cause ... normal mood functioning. Dopamine —mainly involved in controlling movement and aiding the flow of information to the ...

  15. Brain Basics

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    Full Text Available ... Brain Neurotransmitters Everything we do relies on neurons communicating with one another. Electrical impulses and chemical signals ... depression, can occur when this process does not work correctly. Communication between neurons can also be electrical, ...

  16. Brain Basics

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    Full Text Available ... brain and nervous system. Glutamate is an excitatory transmitter: when it is released it increases the chance ... at www.nimh.nih.gov . Glossary action potential —Transmission of signal from the cell body to the ...

  17. Coordinated Gene Expression of Neuroinflammatory and Cell Signaling Markers in Dorsolateral Prefrontal Cortex during Human Brain Development and Aging

    Science.gov (United States)

    Primiani, Christopher T.; Ryan, Veronica H.; Rao, Jagadeesh S.; Cam, Margaret C.; Ahn, Kwangmi; Modi, Hiren R.; Rapoport, Stanley I.

    2014-01-01

    Background Age changes in expression of inflammatory, synaptic, and neurotrophic genes are not well characterized during human brain development and senescence. Knowing these changes may elucidate structural, metabolic, and functional brain processes over the lifespan, as well vulnerability to neurodevelopmental or neurodegenerative diseases. Hypothesis Expression levels of inflammatory, synaptic, and neurotrophic genes in the human brain are coordinated over the lifespan and underlie changes in phenotypic networks or cascades. Methods We used a large-scale microarray dataset from human prefrontal cortex, BrainCloud, to quantify age changes over the lifespan, divided into Development (0 to 21 years, 87 brains) and Aging (22 to 78 years, 144 brains) intervals, in transcription levels of 39 genes. Results Gene expression levels followed different trajectories over the lifespan. Many changes were intercorrelated within three similar groups or clusters of genes during both Development and Aging, despite different roles of the gene products in the two intervals. During Development, changes were related to reported neuronal loss, dendritic growth and pruning, and microglial events; TLR4, IL1R1, NFKB1, MOBP, PLA2G4A, and PTGS2 expression increased in the first years of life, while expression of synaptic genes GAP43 and DBN1 decreased, before reaching plateaus. During Aging, expression was upregulated for potentially pro-inflammatory genes such as NFKB1, TRAF6, TLR4, IL1R1, TSPO, and GFAP, but downregulated for neurotrophic and synaptic integrity genes such as BDNF, NGF, PDGFA, SYN, and DBN1. Conclusions Coordinated changes in gene transcription cascades underlie changes in synaptic, neurotrophic, and inflammatory phenotypic networks during brain Development and Aging. Early postnatal expression changes relate to neuronal, glial, and myelin growth and synaptic pruning events, while late Aging is associated with pro-inflammatory and synaptic loss changes. Thus, comparable

  18. Metformin protects the brain against ischemia/reperfusion injury through PI3K/Akt1/JNK3 signaling pathways in rats.

    Science.gov (United States)

    Ge, Xu-Hua; Zhu, Guo-Ji; Geng, De-Qin; Zhang, Han-Zhi; He, Juan-Mei; Guo, Ai-Zhen; Ma, Lin-Lin; Yu, De-Hua

    2017-03-01

    Although Metformin, a first-line antidiabetic drug, can ameliorate ischemia/reperfusion (I/R) induced brain damage, but how metformin benefits injured hippocampus and the mechanisms are still largely unknown. Therefore, the aim of this study was to investigate the neuroprotective mechanisms of metformin against ischemic brain damage induced by cerebral I/R and to explore whether the Akt-mediated down-regulation of the phosphorylation of JNK3 signaling pathway contributed to the protection provided by metformin. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats. The open field tasks and Morris water maze were used to assess the effect of metformin on anxiety-like behavioral and cognitive impairment after I/R. Cresyl Violet staining was used to examine the survival of hippocampal CA1 pyramidal neurons. Immunoblotting was performed to measure the phosphorylation of Akt1, JNK3, c-Jun and the expression of cleaved caspase-3. Through ischemia/reperfusion (I/R) rat model, we found that metformin could attenuate the deficits of hippocampal related behaviors and inhibit cell apoptosis. The western blot data showed that metformin could promote the activation of Akt1 and reduce the phosphorylation of JNK3 and c-Jun as well as elevation of cleaved caspase-3 in I/R brains. PI3K inhibitor reversed all the protective effects, further indicating that metformin protect hippocampus from ischemic damage through PI3K/Akt1/JNK3/c-Jun signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Fructose-1,6-bisphosphate suppresses lipopolysaccharide-induced expression of ICAM-1 through modulation of toll-like receptor-4 signaling in brain endothelial cells.

    Science.gov (United States)

    Seok, Sun Mi; Park, Tae Yeop; Park, Hye-Si; Baik, Eun Joo; Lee, Soo Hwan

    2015-05-01

    Fructose-1,6-bisphosphate (FBP) is a glycolytic intermediate with salutary effects in various brain injury models, but its neuroprotective mechanism is incompletely understood. In this study, we examined the effects of FBP on the expression of adhesion molecules in cerebrovascular endothelial cells and explored the possible mechanisms therein involved. FBP significantly down-regulated lipopolysaccharide (LPS)-induced expression of adhesion molecules and leukocyte adhesion to brain endothelial cells and inhibited NF-κB activity, which is implicated in the expression of adhesion molecules. FBP abrogated ICAM-1 expression and NF-κB activation induced by macrophage-activating lipopeptide 2-kDa (MALP-2) or overexpression of MyD88 or TRAF6. FBP suppressed TRAF6-induced phosphorylation of TAK1, IKKβ and IκBα, but fail to affect NF-κB activity induced by ectopic expression of IKKβ. In addition, LPS-induced IRAK-1 phosphorylation was inhibited by FBP, suggesting the presence of multiple molecular targets of FBP in MyD88-dependent signaling pathway. FBP significantly attenuated ICAM-1 expression and NF-κB activity induced by poly[I:C] or overexpression of TRIF or TBK1. FBP significantly repressed the expression of interferon-β (IFN-β) and the activation of IFN regulatory factor 3 (IRF3) induced by LPS, poly[I:C] or overexpression of TRIF or TBK1, but fail to affect IRF3 activity induced by ectopic expression of constitutively active IRF3. Overall, our results demonstrate that FBP modulates both MyD88- and TRIF-dependent signaling pathways of TLR4 and subsequent inflammatory responses in brain endothelial cells, providing insight into its neuroprotective mechanism in brain injury associated with inflammation. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Retinoic acid signaling in the brain marks formation of optic projections, maturation of the dorsal telencephalon, and function of limbic sites.

    Science.gov (United States)

    Luo, Tuanlian; Wagner, Elisabeth; Grün, Felix; Dräger, Ursula C

    2004-03-08

    As retinoic acid (RA) is known to regulate the expression of many neuronal proteins, it is likely to influence overall development and function of the brain; few particulars, however, are available about its role in neurobiological contexts due mainly to problems in RA detection. To ask whether the function of RA in the rostral brain is concentrated in particular neurobiological systems, we compared sites of RA synthesis and actions, as detected by RA signaling in reporter mice, for embryonic and adult ages. We found that most sites of RA actions in the forebrain do not colocalize with RA synthesis, consistent with a dominant RA supply by diffusion and the circulation. The changing RA patterns distinguish preferentially two complex functional schemes. (1) Within the visual system when the first optic axons grow toward their targets, RA signaling delineates the topographical adjustment of the retinal map, which is encoded in the coordinates of the visual world, to central visual maps, which are formed in the segmental brain coordinates. (2) The second scheme begins early in forebrain morphogenesis as a distinction of the dorsal telencephalon. With progressing development, and in the adult, the RA patterns then focus on widely distributed structures, most of which belong to the limbic system. These are sites in which emotional perception is combined with higher cognitive processes and in which normal function requires ongoing remodeling of synaptic connections, indicating that the developmental role of RA in promotion of neuronal differentiation programs continues in the adult brain for highly flexible neural circuits. J. Comp. Neurol. 470:297-316, 2004. Copyright 2004 Wiley-Liss, Inc.

  1. Cinnamon counteracts the negative effects of a high fat/high fructose diet on behavior, brain insulin signaling and Alzheimer-associated changes.

    Directory of Open Access Journals (Sweden)

    Richard A Anderson

    Full Text Available Insulin resistance leads to memory impairment. Cinnamon (CN improves peripheral insulin resistance but its effects in the brain are not known. Changes in behavior, insulin signaling and Alzheimer-associated mRNA expression in the brain were measured in male Wistar rats fed a high fat/high fructose (HF/HFr diet to induce insulin resistance, with or without CN, for 12 weeks. There was a decrease in insulin sensitivity associated with the HF/HFr diet that was reversed by CN. The CN fed rats were more active in a Y maze test than rats fed the control and HF/HFr diets. The HF/HFr diet fed rats showed greater anxiety in an elevated plus maze test that was lessened by feeding CN. The HF/HFr diet also led to a down regulation of the mRNA coding for GLUT1 and GLUT3 that was reversed by CN in the hippocampus and cortex. There were increases in Insr, Irs1 and Irs2 mRNA in the hippocampus and cortex due to the HF/HFr diet that were not reversed by CN. Increased peripheral insulin sensitivity was also associated with increased glycogen synthase in both hippocampus and cortex in the control and HF/HFr diet animals fed CN. The HF/HFr diet induced increases in mRNA associated with Alzheimers including PTEN, Tau and amyloid precursor protein (App were also alleviated by CN. In conclusion, these data suggest that the negative effects of a HF/HFr diet on behavior, brain insulin signaling and Alzheimer-associated changes were alleviated by CN suggesting that neuroprotective effects of CN are associated with improved whole body insulin sensitivity and related changes in the brain.

  2. Genome-wide analysis of brain and gonad transcripts reveals changes of key sex reversal-related genes expression and signaling pathways in three stages of Monopterus albus.

    Directory of Open Access Journals (Sweden)

    Wei Chi

    Full Text Available The natural sex reversal severely affects the sex ratio and thus decreases the productivity of the rice field eel (Monopterus albus. How to understand and manipulate this process is one of the major issues for the rice field eel stocking. So far the genomics and transcriptomics data available for this species are still scarce. Here we provide a comprehensive study of transcriptomes of brain and gonad tissue in three sex stages (female, intersex and male from the rice field eel to investigate changes in transcriptional level during the sex reversal process.Approximately 195 thousand unigenes were generated and over 44.4 thousand were functionally annotated. Comparative study between stages provided multiple differentially expressed genes in brain and gonad tissue. Overall 4668 genes were found to be of unequal abundance between gonad tissues, far more than that of the brain tissues (59 genes. These genes were enriched in several different signaling pathways. A number of 231 genes were found with different levels in gonad in each stage, with several reproduction-related genes included. A total of 19 candidate genes that could be most related to sex reversal were screened out, part of these genes' expression patterns were validated by RT-qPCR. The expression of spef2, maats1, spag6 and dmc1 were abundant in testis, but was barely detected in females, while the 17β-hsd12, zpsbp3, gal3 and foxn5 were only expressed in ovary.This study investigated the complexity of brain and gonad transcriptomes in three sex stages of the rice field eel. Integrated analysis of different gene expression and changes in signaling pathways, such as PI3K-Akt pathway, provided crucial data for further study of sex transformation mechanisms.

  3. Genome-wide analysis of brain and gonad transcripts reveals changes of key sex reversal-related genes expression and signaling pathways in three stages of Monopterus albus.

    Science.gov (United States)

    Chi, Wei; Gao, Yu; Hu, Qing; Guo, Wei; Li, Dapeng

    2017-01-01

    The natural sex reversal severely affects the sex ratio and thus decreases the productivity of the rice field eel (Monopterus albus). How to understand and manipulate this process is one of the major issues for the rice field eel stocking. So far the genomics and transcriptomics data available for this species are still scarce. Here we provide a comprehensive study of transcriptomes of brain and gonad tissue in three sex stages (female, intersex and male) from the rice field eel to investigate changes in transcriptional level during the sex reversal process. Approximately 195 thousand unigenes were generated and over 44.4 thousand were functionally annotated. Comparative study between stages provided multiple differentially expressed genes in brain and gonad tissue. Overall 4668 genes were found to be of unequal abundance between gonad tissues, far more than that of the brain tissues (59 genes). These genes were enriched in several different signaling pathways. A number of 231 genes were found with different levels in gonad in each stage, with several reproduction-related genes included. A total of 19 candidate genes that could be most related to sex reversal were screened out, part of these genes' expression patterns were validated by RT-qPCR. The expression of spef2, maats1, spag6 and dmc1 were abundant in testis, but was barely detected in females, while the 17β-hsd12, zpsbp3, gal3 and foxn5 were only expressed in ovary. This study investigated the complexity of brain and gonad transcriptomes in three sex stages of the rice field eel. Integrated analysis of different gene expression and changes in signaling pathways, such as PI3K-Akt pathway, provided crucial data for further study of sex transformation mechanisms.

  4. TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in behavior and plasticity of L2 interneurons in the brain of Drosophila melanogaster.

    Science.gov (United States)

    Kijak, Ewelina; Pyza, Elżbieta

    2017-01-01

    Drosophila melanogaster is a common model used to study circadian rhythms in behavior and circadian clocks. However, numerous circadian rhythms have also been detected in non-clock neurons, especially in the first optic neuropil (lamina) of the fly's visual system. Such rhythms have been observed in the number of synapses and in the structure of interneurons, which exhibit changes in size and shape in a circadian manner. Although the patterns of these changes are known, the mechanism remains unclear. In the present study, we investigated the role of the TOR signaling pathway and autophagy in regulating circadian rhythms based on the behavior and structural plasticity of the lamina L2 monopolar cell dendritic trees. In addition, we examined the cyclic expression of the TOR signaling pathway (Tor, Pi3K class 1, Akt1) and autophagy (Atg5 and Atg7) genes in the fly's brain. We observed that Tor, Atg5 and Atg7 exhibit rhythmic expressions in the brain of wild-type flies in day/night conditions (LD 12:12) that are abolished in per01 clock mutants. The silencing of Tor in per expressing cells shortens a period of the locomotor activity rhythm of flies. In addition, silencing of the Tor and Atg5 genes in L2 cells disrupts the circadian plasticity of the L2 cell dendritic trees measured in the distal lamina. In turn, silencing of the Atg7 gene in L2 cells changes the pattern of this rhythm. Our results indicate that the TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in the behavior and plasticity of neurons in the brain of adult flies.

  5. Brain radiation injury leads to a dose- and time-dependent recruitment of peripheral myeloid cells that depends on CCR2 signaling.

    Science.gov (United States)

    Moravan, Michael J; Olschowka, John A; Williams, Jacqueline P; O'Banion, M Kerry

    2016-02-03

    Cranial radiotherapy is used to treat tumors of the central nervous system (CNS), as well as non-neoplastic conditions such as arterio-venous malformations; however, its use is limited by the tolerance of adjacent normal CNS tissue, which can lead to devastating long-term sequelae for patients. Despite decades of research, the underlying mechanisms by which radiation induces CNS tissue injury remain unclear. Neuroinflammation and immune cell infiltration are a recognized component of the CNS radiation response; however, the extent and mechanisms by which bone marrow-derived (BMD) immune cells participate in late radiation injury is unknown. Thus, we set out to better characterize the response and tested the hypothesis that C-C chemokine receptor type 2 (CCR2) signaling was required for myeloid cell recruitment following brain irradiation. We used young adult C57BL/6 male bone marrow chimeric mice created with donor mice that constitutively express enhanced green fluorescent protein (eGFP). The head was shielded to avoid brain radiation exposure during chimera construction. Radiation dose and time response studies were conducted in wild-type chimeras, and additional experiments were performed with chimeras created using donor marrow from CCR2 deficient, eGFP-expressing mice. Infiltrating eGFP+ cells were identified and quantified using immunofluorescent microscopy. Brain irradiation resulted in a dose- and time-dependent infiltration of BMD immune cells (predominately myeloid) that began at 1 month and persisted until 6 months following ≥15 Gy brain irradiation. Infiltration was limited to areas that were directly exposed to radiation. CCR2 signaling loss resulted in decreased numbers of infiltrating cells at 6 months that appeared to be restricted to cells also expressing major histocompatibility complex class II molecules. The potential roles played by infiltrating immune cells are of current importance due to increasing interest in immunotherapeutic approaches

  6. Separating heart and brain: on the reduction of physiological noise from multichannel functional near-infrared spectroscopy (fNIRS) signals

    Science.gov (United States)

    Bauernfeind, G.; Wriessnegger, S. C.; Daly, I.; Müller-Putz, G. R.

    2014-10-01

    Objective. Functional near-infrared spectroscopy (fNIRS) is an emerging technique for the in vivo assessment of functional activity of the cerebral cortex as well as in the field of brain-computer interface (BCI) research. A common challenge for the utilization of fNIRS in these areas is a stable and reliable investigation of the spatio-temporal hemodynamic patterns. However, the recorded patterns may be influenced and superimposed by signals generated from physiological processes, resulting in an inaccurate estimation of the cortical activity. Up to now only a few studies have investigated these influences, and still less has been attempted to remove/reduce these influences. The present study aims to gain insights into the reduction of physiological rhythms in hemodynamic signals (oxygenated hemoglobin (oxy-Hb), deoxygenated hemoglobin (deoxy-Hb)). Approach. We introduce the use of three different signal processing approaches (spatial filtering, a common average reference (CAR) method; independent component analysis (ICA); and transfer function (TF) models) to reduce the influence of respiratory and blood pressure (BP) rhythms on the hemodynamic responses. Main results. All approaches produce large reductions in BP and respiration influences on the oxy-Hb signals and, therefore, improve the contrast-to-noise ratio (CNR). In contrast, for deoxy-Hb signals CAR and ICA did not improve the CNR. However, for the TF approach, a CNR-improvement in deoxy-Hb can also be found. Significance. The present study investigates the application of different signal processing approaches to reduce the influences of physiological rhythms on the hemodynamic responses. In addition to the identification of the best signal processing method, we also show the importance of noise reduction in fNIRS data.

  7. Signal propagation in cortical networks: a digital signal processing approach.

    Science.gov (United States)

    Rodrigues, Francisco Aparecido; da Fontoura Costa, Luciano

    2009-01-01

    This work reports a digital signal processing approach to representing and modeling transmission and combination of signals in cortical networks. The signal dynamics is modeled in terms of diffusion, which allows the information processing undergone between any pair of nodes to be fully characterized in terms of a finite impulse response (FIR) filter. Diffusion without and with time decay are investigated. All filters underlying the cat and macaque cortical organization are found to be of low-pass nature, allowing the cortical signal processing to be summarized in terms of the respective cutoff frequencies (a high cutoff frequency meaning little alteration of signals through their intermixing). Several findings are reported and discussed, including the fact that the incorporation of temporal activity decay tends to provide more diversified cutoff frequencies. Different filtering intensity is observed for each community in those networks. In addition, the brain regions involved in object recognition tend to present the highest cutoff frequencies for both the cat and macaque networks.

  8. Brain signal analysis using EEG and Entropy to study the effect of physical and mental tasks on cognitive performance

    Directory of Open Access Journals (Sweden)

    Dineshen Chuckravanen

    2015-07-01

    Full Text Available Some theoretical control models posit that the fatigue which is developed during physical activity is not always peripheral and it is the brain which causes this feeling of fatigue. This fatigue develops due to a decrease of metabolic resources to and from the brain that modulates physical performance. Therefore, this research was conducted to find out if there was finite level ofmetabolic energy resources in the brain, by performing both mental and physical activities to exhaustion. It was found that there was an overflow of information during the exercise-involved experiment. The circular relationship between fatigue, cognitive performance and arousal state insinuates that one should apply more effort to maintain performance levels which would require more energy resources that eventually accelerates the development of fatigue. Thus, there appeared to be a limited amount of energy resources in the brain as shown by the cognitive performance of the participants.

  9. Abnormal activity of the MAPK- and cAMP-associated signaling pathways in frontal cortical areas in postmortem brain in schizophrenia.

    Science.gov (United States)

    Funk, Adam J; McCullumsmith, Robert E; Haroutunian, Vahram; Meador-Woodruff, James H

    2012-03-01

    Recent evidence suggests that schizophrenia may result from alterations of integration of signaling mediated by multiple neurotransmitter systems. Abnormalities of associated intracellular signaling pathways may contribute to the pathophysiology of schizophrenia. Proteins and phospho-proteins comprising mitogen activated protein kinase (MAPK) and 3'-5'-cyclic adenosine monophosphate (cAMP)-associated signaling pathways may be abnormally expressed in the anterior cingulate (ACC) and dorsolateral prefrontal cortex (DLPFC) in schizophrenia. Using western blot analysis we examined proteins of the MAPK- and cAMP-associated pathways in these two brain regions. Postmortem samples were used from a well-characterized collection of elderly patients with schizophrenia (ACC=36, DLPFC=35) and a comparison (ACC=33, DLPFC=31) group. Near-infrared intensity of IR-dye labeled secondary antisera bound to targeted proteins of the MAPK- and cAMP-associated signaling pathways was measured using LiCor Odyssey imaging system. We found decreased expression of Rap2, JNK1, JNK2, PSD-95, and decreased phosphorylation of JNK1/2 at T183/Y185 and PSD-95 at S295 in the ACC in schizophrenia. In the DLPFC, we found increased expression of Rack1, Fyn, Cdk5, and increased phosphorylation of PSD-95 at S295 and NR2B at Y1336. MAPK- and cAMP-associated molecules constitute ubiquitous intracellular signaling pathways that integrate extracellular stimuli, modify receptor expression and function, and regulate cell survival and neuroplasticity. These data suggest abnormal activity of the MAPK- and cAMP-associated pathways in frontal cortical areas in schizophrenia. These alterations may underlie the hypothesized hypoglutamatergic function in this illness. Together with previous findings, these data suggest that abnormalities of intracellular signaling pathways may contribute to the pathophysiology of schizophrenia.

  10. 5-HT(2C) antagonism blocks blood oxygen level-dependent pharmacological-challenge magnetic resonance imaging signal in rat brain areas related to feeding.

    Science.gov (United States)

    Stark, Jennifer A; McKie, Shane; Davies, Karen E; Williams, Steve R; Luckman, Simon M

    2008-01-01

    In this study, pharmacological-challenge magnetic resonance imaging was used to further characterize the central action of serotonin on feeding. In both feeding and pharmacological-challenge magnetic resonance imaging experiments, we combined 5-HT(1B/2C) agonist m-chlorophenylpiperazine (mCPP) challenge with pre-treatment with the selective 5-HT(1B) and 5-HT(2C) receptor antagonists, SB 224289 (2.5 mg/kg) and SB 242084 (2 mg/kg), respectively. Subcutaneous injection of mCPP (3 mg/kg) completely blocked fast-induced refeeding in freely behaving, non-anaesthetized male rats, an effect that was not modified by the 5-HT(1B) receptor antagonist but was partially reversed by the 5-HT(2C) receptor antagonist. mCPP alone induced both positive and negative blood oxygen level-dependent (BOLD) responses in the brains of anaesthetized rats, including in the limbic system and basal ganglia. Overall, the 5-HT(2C) antagonist SB 242084 reversed the effects elicited by mCPP, whereas the 5-HT(1B) antagonist SB 224289 had virtually no impact. SB 242084 eliminated BOLD signal in nuclei associated with the limbic system and diminished activation in basal ganglia. In addition, BOLD signal was returned to baseline levels in the cortical regions and cerebellum. These results suggest that mCPP may reduce food intake by acting specifically on brain circuits that are modulated by 5-HT(2C) receptors in the rat.

  11. Neuroenergetics: How energy constraints shape brain function

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    The nervous system consumes a disproportionate fraction of the resting body’s energy production. In humans, the brain represents 2% of the body’s mass, yet it accounts for ~20% of the total oxygen consumption. Expansion in the size of the brain relative to the body and an increase in the number of connections between neurons during evolution underpin our cognitive powers and are responsible for our brains’ high metabolic rate. The molecules at the center of cellular energy metabolism also act as intercellular signals and constitute an important communication pathway, coordinating for instance the immune surveillance of the brain. Despite the significance of energy consumption in the nervous system, how energy constrains and shapes brain function is often under appreciated. I will illustrate the importance of brain energetics and metabolism with two examples from my recent work. First, I will show how the brain trades information for energy savings in the visual pathway. Indeed, a significant fraction ...

  12. Changes in brain G proteins and colonic sympathetic neural signaling in chronic-acute combined stress rat model of irritable bowel syndrome (IBS).

    Science.gov (United States)

    Zou, Ning; Lv, Hong; Li, Ji; Yang, Ning; Xue, Hong; Zhu, Jinxia; Qian, Jiaming

    2008-12-01

    The role of the brain-gut axis interaction in the pathogenesis of irritable bowel syndrome (IBS) is not well understood. To examine this possibility, a novel rat model of IBS subjected to both chronic and acute stress (CAS) was established. G proteins play a crucial role in the pathophysiology of depression. The alpha 2A adrenoceptor (alpha(2A)-AR) and the norepinephrine reuptake transporter (NET) determine the sympathetic signal activity. It is conceivable that stress may induce brain G proteins, colonic alpha(2A)-ARs, and NET abnormal expression, which may be responsible for the abnormalities in IBS. Colonic motility, visceral sensation, and secretion were assessed by counting fecal pellets, abdominal muscle contractions in response to colorectal balloon distension (CRD), and short-circuit current study, respectively. Western blot analysis was used to investigate the expression of G proteins, alpha(2A)-ARs, and NET. Compared with control animals, the colonic epithelial secretion, fecal pellets, and numbers of abdominal muscle contraction induced by CRD were significantly higher in both acute stress only (AS) and CAS rats. However, the G proteins, alpha(2A)-AR, and NET expression changed differently in AS and CAS rats. We showed that exposure to either AS or CAS would cause the increase of secretion, motility, and sensation, but the change of protein expression in brain-gut axis was different. It may be responsible for the pathogenesis of IBS.

  13. Cocaine-associated odor cue re-exposure increases blood oxygenation level dependent signal in memory and reward regions of the maternal rat brain.

    Science.gov (United States)

    Caffrey, Martha K; Febo, Marcelo

    2014-01-01

    Cue triggered relapse during the postpartum period can negatively impact maternal care. Given the high reward value of pups in maternal rats, we designed an fMRI experiment to test whether offspring presence reduces the neural response to a cocaine associated olfactory cue. Cocaine conditioned place preference was carried out before pregnancy in the presence of two distinct odors that were paired with cocaine or saline (+Cue and -Cue). The BOLD response to +Cue and -Cue was measured in dams on postpartum days 2-4. Odor cues were delivered to dams in the absence and then the presence of pups. Our data indicate that several limbic and cognitive regions of the maternal rat brain show a greater BOLD signal response to a +Cue versus -Cue. These include dorsal striatum, prelimbic cortex, parietal cortex, habenula, bed nucleus of stria terminalis, lateral septum and the mediodorsal and the anterior thalamic nucleus. Of the aforementioned brain regions, only the parietal cortex of cocaine treated dams showed a significant modulatory effect of pup presence. In this area of the cortex, cocaine exposed maternal rats showed a greater BOLD activation in response to the +Cue in the presence than in the absence of pups. Specific regions of the cocaine exposed maternal rat brain are strongly reactive to drug associated cues. The regions implicated in cue reactivity have been previously reported in clinical imaging work, and previous work supports their role in various motivational and cognitive functions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Acute up-regulation of the rat brain somatostatin receptor-effector system by leptin is related to activation of insulin signaling and may counteract central leptin actions.

    Science.gov (United States)

    Perianes-Cachero, A; Burgos-Ramos, E; Puebla-Jiménez, L; Canelles, S; Frago, L M; Hervás-Aguilar, A; de Frutos, S; Toledo-Lobo, M V; Mela, V; Viveros, M P; Argente, J; Chowen, J A; Arilla-Ferreiro, E; Barrios, V

    2013-11-12

    Leptin and somatostatin (SRIF) have opposite effects on food seeking and ingestive behaviors, functions partially regulated by the frontoparietal cortex and hippocampus. Although it is known that the acute suppression of food intake mediated by leptin decreases with time, the counter-regulatory mechanisms remain unclear. Our aims were to analyze the effect of acute central leptin infusion on the SRIF receptor-effector system in these areas and the implication of related intracellular signaling mechanisms in this response. We studied 20 adult male Wister rats including controls and those treated intracerebroventricularly with a single dose of 5 μg of leptin and sacrificed 1 or 6h later. Density of SRIF receptors was unchanged at 1h, whereas leptin increased the density of SRIF receptors at 6h, which was correlated with an elevated capacity of SRIF to inhibit forskolin-stimulated adenylyl cyclase activity in both areas. The functional capacity of SRIF receptors was unaltered as cell membrane levels of αi1 and αi2 subunits of G inhibitory proteins were unaffected in both brain areas. The increased density of SRIF receptors was due to enhanced SRIF receptor subtype 2 (sst2) protein levels that correlated with higher mRNA levels for this receptor. These changes in sst2 mRNA levels were concomitant with increased activation of the insulin signaling, c-Jun and cyclic AMP response element-binding protein (CREB); however, activation of signal transducer and activator of transcription 3 was reduced in the cortex and unchanged in the hippocampus and suppressor of cytokine signaling 3 remained unchanged in these areas. In addition, the leptin antagonist L39A/D40A/F41A blocked the leptin-induced changes in SRIF receptors, leptin signaling and CREB activation. In conclusion, increased activation of insulin signaling after leptin infusion is related to acute up-regulation of the SRIF receptor-effector system that may antagonize short-term leptin actions in the rat brain

  15. Melatonin Stimulates the SIRT1/Nrf2 Signaling Pathway Counteracting Lipopolysaccharide (LPS)-Induced Oxidative Stress to Rescue Postnatal Rat Brain.

    Science.gov (United States)

    Shah, Shahid Ali; Khan, Mehtab; Jo, Myeung-Hoon; Jo, Min Gi; Amin, Faiz Ul; Kim, Myeong Ok

    2017-01-01

    Lipopolysaccharide (LPS) induces oxidative stress and neuroinflammation both in vivo and in vitro. Here, we provided the first detailed description of the mechanism of melatonin neuroprotection against LPS-induced oxidative stress, acute neuroinflammation, and neurodegeneration in the hippocampal dentate gyrus (DG) region of the postnatal day 7 (PND7) rat brain. The neuroprotective effects of melatonin against LPS-induced neurotoxicity were analyzed using multiple research techniques, including Western blotting, immunofluorescence, and enzyme-linked immunosorbent assays (ELISAs) in PND7 rat brain homogenates and BV2 cell lysates in vitro. We also used EX527 to inhibit silent information regulator transcript-1 (SIRT1). A single intraperitoneal (i.p) injection of LPS to PND7 rats significantly induced glial cell activation, acute neuroinflammation, reactive oxygen species (ROS) production and apoptotic neurodegeneration in hippocampal DG region after 4 h. However, the coadministration of melatonin significantly inhibited both LPS-induced acute neuroinflammation and apoptotic neurodegeneration and improved synaptic dysfunction in the hippocampal DG region of PND7 rats. Most importantly, melatonin stimulated the SIRT1/Nrf2 (nuclear factor-erythroid 2-related factor 2) signaling pathway to reduce LPS-induced ROS generation. The beneficial effects of melatonin were further confirmed in LPS-stimulated BV2 microglia cell lines in vitro using EX527 as an inhibitor of SIRT1. LPS-induced oxidative stress, Nrf2 inhibition, and neuroinflammation are SIRT1-dependent in BV2 microglia cell lines. These results demonstrated that melatonin treatment rescued the hippocampal DG region of PND7 rat brains against LPS-induced oxidative stress damage, acute neuroinflammation, and apoptotic neurodegeneration via SIRT1/Nrf2 signaling pathway activation. © 2016 John Wiley & Sons Ltd.

  16. A common human micro-opioid receptor genetic variant diminishes the receptor signaling efficacy in brain regions processing the sensory information of pain.

    Science.gov (United States)

    Oertel, Bruno Georg; Kettner, Mattias; Scholich, Klaus; Renné, Christoph; Roskam, Bianca; Geisslinger, Gerd; Schmidt, Peter Harald; Lötsch, Jörn

    2009-03-06

    The single nucleotide polymorphism 118A>G of the human micro-opioid receptor gene OPRM1, which leads to an exchange of the amino acid asparagine (N) to aspartic acid (D) at position 40 of the extracellular receptor region, alters the in vivo effects of opioids to different degrees in pain-processing brain regions. The most pronounced N40D effects were found in brain regions involved in the sensory processing of pain intensity. Using the mu-opioid receptor-specific agonist DAMGO, we analyzed the micro-opioid receptor signaling, expression, and binding affinity in human brain tissue sampled postmortem from the secondary somatosensory area (SII) and from the ventral posterior part of the lateral thalamus, two regions involved in the sensory processing and transmission of nociceptive information. We show that the main effect of the N40D micro-opioid receptor variant is a reduction of the agonist-induced receptor signaling efficacy. In the SII region of homo- and heterozygous carriers of the variant 118G allele (n=18), DAMGO was only 62% as efficient (p=0.002) as in homozygous carriers of the wild-type 118A allele (n=15). In contrast, the number of [3H]DAMGO binding sites was unaffected. Hence, the micro-opioid receptor G-protein coupling efficacy in SII of carriers of the 118G variant was only 58% as efficient as in homozygous carriers of the 118A allele (pG SNP. In conclusion, we provide a molecular basis for the reduced clinical effects of opioid analgesics in carriers of mu-opioid receptor variant N40D.

  17. Microglia Polarization, Gene-Environment Interactions and Wnt/β-Catenin Signaling: Emerging Roles of Glia-Neuron and Glia-Stem/Neuroprogenitor Crosstalk for Dopaminergic Neurorestoration in Aged Parkinsonian Brain

    Directory of Open Access Journals (Sweden)

    Francesca L'Episcopo

    2018-02-01

    Full Text Available Neuroinflammatory processes are recognized key contributory factors in Parkinson's disease (PD physiopathology. While the causes responsible for the progressive loss of midbrain dopaminergic (mDA neuronal cell bodies in the subtantia nigra pars compacta are poorly understood, aging, genetics, environmental toxicity, and particularly inflammation, represent prominent etiological factors in PD development. Especially, reactive astrocytes, microglial cells, and infiltrating monocyte-derived macrophages play dual beneficial/harmful effects, via a panel of pro- or anti-inflammatory cytokines, chemokines, neurotrophic and neurogenic transcription factors. Notably, with age, microglia may adopt a potent neurotoxic, pro-inflammatory “primed” (M1 phenotype when challenged with inflammatory or neurotoxic stimuli that hamper brain's own restorative potential and inhibit endogenous neurorepair mechanisms. In the last decade we have provided evidence for a major role of microglial crosstalk with astrocytes, mDA neurons and neural stem progenitor cells (NSCs in the MPTP- (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- mouse model of PD, and identified Wnt/β-catenin signaling, a pivotal morphogen for mDA neurodevelopment, neuroprotection, and neuroinflammatory modulation, as a critical actor in glia-neuron and glia-NSCs crosstalk. With age however, Wnt signaling and glia-NSC-neuron crosstalk become dysfunctional with harmful consequences for mDA neuron plasticity and repair. These findings are of importance given the deregulation of Wnt signaling in PD and the emerging link between most PD related genes, Wnt signaling and inflammation. Especially, in light of the expanding field of microRNAs and inflammatory PD-related genes as modulators of microglial-proinflammatory status, uncovering the complex molecular circuitry linking PD and neuroinflammation will permit the identification of new druggable targets for the cure of the disease. Here we summarize

  18. Transient signaling of Erk1/2, Akt and PLCgamma induced by nerve growth factor in brain capillary endothelial cells.

    Science.gov (United States)

    Lecht, Shimon; Arien-Zakay, Hadar; Wagenstein, Yoav; Inoue, Seiji; Marcinkiewicz, Cezary; Lelkes, Peter I; Lazarovici, Philip

    2010-01-01

    Cumulative evidences suggest that nerve growth factor (NGF) promotes angiogenic effects such as proliferation and migration of endothelial cells (ECs) from different vascular beds, induces capillary sprouting in chorioallantoic membrane and improves in vivo vascularization in a hind-limb ischemic model. In the present study, we sought to investigate the signaling properties of NGF in a microcapillary ECs model compared to those of a neuronal model. NGF-induced phosphorylation of signaling molecules Erk1/2, Akt and PLCgamma were measured using Western blotting and compared between mouse NGF (mNGF) and snake venom NGF analogues. NGFs-induced signaling was TrkA mediated as evident by inhibition with the TrkA antagonist K252a. NGF and its analogues-induced signaling in ECs were characterized by a transient effect in contrast to a prolonged stimulation in neuronal cells. The potency of mouse, cobra and viper NGFs to induce Erk1/2 phosphorylation in ECs was higher than in neurons. In ECs, mNGF exhibited the highest efficacy of stimulation of Erk1/2 phosphorylation, followed by viper and cobra NGFs. The efficacy of stimulation of Erk1/2 phosphorylation measured with neurons was opposite from that in ECs. NGF-induced temporal signaling differences between ECs and neurons may explain the dual vascular and neurotrophic effects of this growth factor. Copyright 2010 Elsevier Inc. All rights reserved.

  19. Regulation of differentiation flux by Notch signalling influences the number of dopaminergic neurons in the adult brain

    Directory of Open Access Journals (Sweden)

    Niurka Trujillo-Paredes

    2016-03-01

    Full Text Available Notch signalling is a well-established pathway that regulates neurogenesis. However, little is known about the role of Notch signalling in specific neuronal differentiation. Using Dll1 null mice, we found that Notch signalling has no function in the specification of mesencephalic dopaminergic neural precursor cells (NPCs, but plays an important role in regulating their expansion and differentiation into neurons. Premature neuronal differentiation was observed in mesencephalons of Dll1-deficient mice or after treatment with a Notch signalling inhibitor. Coupling between neurogenesis and dopaminergic differentiation was indicated from the coincident emergence of neuronal and dopaminergic markers. Early in differentiation, decreasing Notch signalling caused a reduction in NPCs and an increase in dopaminergic neurons in association with dynamic changes in the proportion of sequentially-linked dopaminergic NPCs (Msx1/2+, Ngn2+, Nurr1+. These effects in differentiation caused a significant reduction in the number of dopaminergic neurons produced. Accordingly, Dll1 haploinsufficient adult mice, in comparison with their wild-type littermates, have a consistent reduction in neuronal density that was particularly evident in the substantia nigra pars compacta. Our results are in agreement with a mathematical model based on a Dll1-mediated regulatory feedback loop between early progenitors and their dividing precursors that controls the emergence and number of dopaminergic neurons.

  20. The Mitochondrial Uncoupler DNP Triggers Brain Cell mTOR Signaling Network Reprogramming and CREB Pathway Upregulation

    OpenAIRE

    Liu, Dong; Zhang, Yongqing; Gharavi, Robert; Park, Hee Ra; Lee, Jaewon; Siddiqui, Sana; Telljohann, Richard; Nassar, Matthew R.; Cutler, Roy G.; Kevin G Becker; Mark P Mattson

    2015-01-01

    Mitochondrial metabolism is highly responsive to nutrient availability and ongoing activity in neuronal circuits. The molecular mechanisms by which brain cells respond to an increase in cellular energy expenditure are largely unknown. Mild mitochondrial uncoupling enhances cellular energy expenditure in mitochondria and can be induced with 2, 4-dinitrophenol (DNP), a proton ionophore previously used for weight loss. We found that DNP treatment reduces mitochondrial membrane potential, increas...

  1. Traveling waves and trial averaging: the nature of single-trial and averaged brain responses in large-scale cortical signals.

    Science.gov (United States)

    Alexander, David M; Jurica, Peter; Trengove, Chris; Nikolaev, Andrey R; Gepshtein, Sergei; Zvyagintsev, Mikhail; Mathiak, Klaus; Schulze-Bonhage, Andreas; Ruescher, Johanna; Ball, Tonio; van Leeuwen, Cees

    2013-06-01

    Analyzing single trial brain activity remains a challenging problem in the neurosciences. We gain purchase on this problem by focusing on globally synchronous fields in within-trial evoked brain activity, rather than on localized peaks in the trial-averaged evoked response (ER). We analyzed data from three measurement modalities, each with different spatial resolutions: magnetoencephalogram (MEG), electroencephalogram (EEG) and electrocorticogram (ECoG). We first characterized the ER in terms of summation of phase and amplitude components over trials. Both contributed to the ER, as expected, but the ER topography was dominated by the phase component. This means the observed topography of cross-trial phase will not necessarily reflect the phase topography within trials. To assess the organization of within-trial phase, traveling wave (TW) components were quantified by computing the phase gradient. TWs were intermittent but ubiquitous in the within-trial evoked brain activity. At most task-relevant times and frequencies, the within-trial phase topography was described better by a TW than by the trial-average of phase. The trial-average of the TW components also reproduced the topography of the ER; we suggest that the ER topography arises, in large part, as an average over TW behaviors. These findings were consistent across the three measurement modalities. We conclude that, while phase is critical to understanding the topography of event-related activity, the preliminary step of collating cortical signals across trials can obscure the TW components in brain activity and lead to an underestimation of the coherent motion of cortical fields. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Angiotensin II receptor subtypes are coupled with distinct signal-transduction mechanisms in neurons and astrocytes from rat brain

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    Sumners, C.; Wei Tang; Zelezna, B.; Raizada, M.K. (Univ. of Florida, Gainesville (United States))

    1991-09-01

    Both neurons and astrocytes contain specific receptors for angiotensin II (AII). The authors used selective ligands for the AT{sub 1} and AT{sub 2} types of AII receptors to investigate the expression of functional receptor subtypes in astrocyte cultures and neuron cultures from 1-day-old (neonatal) rat brain. In astrocyte cultures, competition of {sup 125}I-labeled AII ({sup 125}I-AII) specific binding with AT{sub 1} (DuP753) or AT{sub 2} {l brace}PD123177, CGP42112A, (Phe(p-NH{sub 2}){sup 6})AII{r brace} selective receptor ligands revealed a potency series of AII > DuP753 > > > CGP42112A > (Phe(p-NH{sub 2}){sup 6})AII > PD123177. These results suggest a predominance of the AT{sub 1} receptor subtype in neonatal astrocytes. {sup 125}I-AII specific binding to neonate neuronal cultures was reduced 73-84% by 1 {mu} MPD123177, and the residual {sup 125}I-AII specific binding was eliminated by DuP753. The results suggest that astrocyte cultures from neonatal rat brains contain predominantly AT{sub 1} receptors that are coupled to a stimulation of inositophospholipid hydrolysis. In contrast, neuron cultures from neonatal rat brain contain mostly AT{sub 2} receptors that are coupled to a reduction in basal cGMP levels, but a smaller population of AT{sub 1} receptors is also present in these neurons.

  3. Group B streptococcal beta-hemolysin/cytolysin activates neutrophil signaling pathways in brain endothelium and contributes to development of meningitis.

    Science.gov (United States)

    Doran, Kelly S; Liu, George Y; Nizet, Victor

    2003-09-01

    Meningitis occurs when blood-borne pathogens cross the blood-brain barrier (BBB) in a complex interplay between endothelial cells and microbial gene products. We sought to understand the initial response of the BBB to the human meningeal pathogen group B Streptococcus (GBS) and the organism's major virulence factors, the exopolysaccharide capsule and the beta-hemolysin/cytolysin toxin (beta-h/c). Using oligonucleotide microarrays, we found that GBS infection of human brain microvascular endothelial cells (HBMEC) induced a highly specific and coordinate set of genes including IL-8, Groalpha, Grobeta, IL-6, GM-CSF, myeloid cell leukemia sequence-1 (Mcl-1), and ICAM-1, which act to orchestrate neutrophil recruitment, activation, and enhanced survival. Most strikingly, infection with a GBS strain lacking beta-h/c resulted in a marked reduction in expression of genes involved in the immune response, while the unencapsulated strain generally induced similar or greater expression levels for the same subset of genes. Cell-free bacterial supernatants containing beta-h/c activity induced IL-8 release, identifying this toxin as a principal provocative factor for BBB activation. These findings were further substantiated in vitro and in vivo. Neutrophil migration across polar HBMEC monolayers was stimulated by GBS and its beta-h/c through a process involving IL-8 and ICAM-1. In a murine model of hematogenous meningitis, mice infected with beta-h/c mutants exhibited lower mortality and decreased brain bacterial counts compared with mice infected with the corresponding WT GBS strains.

  4. Tetramethylpyrazine Protects Against Oxygen-Glucose Deprivation-Induced Brain Microvascular Endothelial Cells Injury via Rho/Rho-kinase Signaling Pathway.

    Science.gov (United States)

    Yang, Guang; Qian, Chen; Wang, Ning; Lin, Chenyu; Wang, Yan; Wang, Guangyun; Piao, Xinxin

    2017-05-01

    Tetramethylpyrazine (TMP, also known as Ligustrazine), which is isolated from Chinese Herb Medicine Ligustium wollichii Franchat (Chuan Xiong), has been widely used in China for the treatment of ischemic stroke by Chinese herbalists. Brain microvascular endothelial cells (BMECs) are the integral parts of the blood-brain barrier (BBB), protecting BMECs against oxygen-glucose deprivation (OGD) which is important for the treatment of ischemic stroke. Here, we investigated the protective mechanisms of TMP, focusing on OGD-injured BMECs and the Rho/Rho-kinase (Rho-associated kinases, ROCK) signaling pathway. The model of OGD-injured BMECs was established in this study. BMECs were identified by von Willebrand factor III staining and exposed to fasudil, or TMP at different concentrations (14.3, 28.6, 57.3 µM) for 2 h before 24 h of OGD injury. The effect of each treatment was examined by cell viability assays, measurement of intracellular reactive oxygen species (ROS), and transendothelial electric resistance and western blot analysis (caspase-3, endothelial nitric oxide synthase (eNOS), RhoA, Rac1). Our results show that TMP significantly attenuated apoptosis and the permeability of BMECs induced by OGD. In addition, TMP could notably down-regulate the characteristic proteins in Rho/ROCK signaling pathway such as RhoA and Rac1, which triggered abnormal changes of eNOS and ROS, respectively. Altogether, our results show that TMP has a strong protective effect against OGD-induced BMECs injury and suggest that the mechanism might be related to the inhibition of the Rho/ROCK signaling pathway.

  5. The Triangle of Death in Alzheimer's Disease Brain: The Aberrant Cross-Talk Among Energy Metabolism, Mammalian Target of Rapamycin Signaling, and Protein Homeostasis Revealed by Redox Proteomics.

    Science.gov (United States)

    Di Domenico, Fabio; Barone, Eugenio; Perluigi, Marzia; Butterfield, D Allan

    2017-03-10

    Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder and represents one of the most disabling conditions. AD shares many features in common with systemic insulin resistance diseases, suggesting that it can be considered as a metabolic disease, characterized by reduced insulin-stimulated growth and survival signaling, increased oxidative stress (OS), proinflammatory cytokine activation, mitochondrial dysfunction, impaired energy metabolism, and altered protein homeostasis. Recent Advances: Reduced glucose utilization and energy metabolism in AD have been associated with the buildup of amyloid-β peptide and hyperphosphorylated tau, increased OS, and the accumulation of unfolded/misfolded proteins. Mammalian target of rapamycin (mTOR), which is aberrantly activated in AD since early stages, plays a key role during AD neurodegeneration by, on one side, inhibiting insulin signaling as a negative feedback mechanism and, on the other side, regulating protein homeostasis (synthesis/clearance). It is likely that the concomitant and mutual alterations of energy metabolism-mTOR signaling-protein homeostasis might represent a self-sustaining triangle of harmful events that trigger the degeneration and death of neurons and the development and progression of AD. Intriguingly, the altered cross-talk between the components of such a triangle of death, beyond altering the redox homeostasis of the neuron, is further exacerbated by increased levels of OS that target and impair key components of the pathways involved. Redox proteomic studies in human samples and animal models of AD-like dementia led to identification of oxidatively modified components of the pathways composing the triangle of death, therefore revealing the crucial role of OS in fueling this aberrant vicious cycle. The identification of compounds able to restore the function of the pathways targeted by oxidative damage might represent a valuable therapeutic approach to slow or delay AD. Antioxid

  6. Classification of EEG-P300 Signals Extracted from Brain Activities in BCI Systems Using ν-SVM and BLDA Algorithms

    Directory of Open Access Journals (Sweden)

    Ali MOMENNEZHAD

    2014-06-01

    Full Text Available In this paper, a linear predictive coding (LPC model is used to improve classification accuracy, convergent speed to maximum accuracy, and maximum bitrates in brain computer interface (BCI system based on extracting EEG-P300 signals. First, EEG signal is filtered in order to eliminate high frequency noise. Then, the parameters of filtered EEG signal are extracted using LPC model. Finally, the samples are reconstructed by LPC coefficients and two classifiers, a Bayesian Linear discriminant analysis (BLDA, and b the υ-support vector machine (υ-SVM are applied in order to classify. The proposed algorithm performance is compared with fisher linear discriminant analysis (FLDA. Results show that the efficiency of our algorithm in improving classification accuracy and convergent speed to maximum accuracy are much better. As example at the proposed algorithms, respectively BLDA with LPC model and υ-SVM with LPC model with8 electrode configuration for subject S1 the total classification accuracy is improved as 9.4% and 1.7%. And also, subject 7 at BLDA and υ-SVM with LPC model algorithms (LPC+BLDA and LPC+ υ-SVM after block 11th converged to maximum accuracy but Fisher Linear Discriminant Analysis (FLDA algorithm did not converge to maximum accuracy (with the same configuration. So, it can be used as a promising tool in designing BCI systems.

  7. In Vitro Treatment of Melanoma Brain Metastasis by Simultaneously Targeting the MAPK and PI3K Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Inderjit Daphu

    2014-05-01

    Full Text Available Malignant melanoma is the most lethal form of skin cancer, with a high propensity to metastasize to the brain. More than 60% of melanomas have the BRAFV600E mutation, which activates the mitogen-activated protein kinase (MAPK pathway [1]. In addition, increased PI3K (phosphoinositide 3-kinase pathway activity has been demonstrated, through the loss of activity of the tumor suppressor gene, PTEN [2]. Here, we treated two melanoma brain metastasis cell lines, H1_DL2, harboring a BRAFV600E mutation and PTEN loss, and H3, harboring WT (wild-type BRAF and PTEN loss, with the MAPK (BRAF inhibitor vemurafenib and the PI3K pathway associated mTOR inhibitor temsirolimus. Combined use of the drugs inhibited tumor cell growth and proliferation in vitro in H1_DL2 cells, compared to single drug treatment. Treatment was less effective in the H3 cells. Furthermore, a strong inhibitory effect on the viability of H1_DL2 cells, when grown as 3D multicellular spheroids, was seen. The treatment inhibited the expression of pERK1/2 and reduced the expression of pAKT and p-mTOR in H1_DL2 cells, confirming that the MAPK and PI3K pathways were inhibited after drug treatment. Microarray experiments followed by principal component analysis (PCA mapping showed distinct gene clustering after treatment, and cell cycle checkpoint regulators were affected. Global gene analysis indicated that functions related to cell survival and invasion were influenced by combined treatment. In conclusion, we demonstrate for the first time that combined therapy with vemurafenib and temsirolimus is effective on melanoma brain metastasis cells in vitro. The presented results highlight the potential of combined treatment to overcome treatment resistance that may develop after vemurafenib treatment of melanomas.

  8. Conservative nature of oestradiol signalling pathways in the brain lobes of octopus vulgaris involved in reproduction, learning and motor coordination.

    Science.gov (United States)

    De Lisa, E; Paolucci, M; Di Cosmo, A

    2012-02-01

    Oestradiol plays crucial roles in the mammalian brain by modulating reproductive behaviour, neural plasticity and pain perception. The cephalopod Octopus vulgaris is considered, along with its relatives, to be the most behaviourally advanced invertebrate, although the neurophysiological basis of its behaviours, including pain perception, remain largely unknown. In the present study, using a combination of molecular and imaging techniques, we found that oestradiol up-regulated O. vulgaris gonadotrophin-releasing hormone (Oct-GnRH) and O. vulgaris oestrogen receptor (Oct-ER) mRNA levels in the olfactory lobes; in turn, Oct-ER mRNA was regulated by NMDA in lobes involved in learning and motor coordination. Fluorescence resonance energy transfer analysis revealed that oestradiol binds Oct-ER causing conformational modifications and nuclear translocation consistent with the classical genomic mechanism of the oestrogen receptor. Moreover, oestradiol triggered a calcium influx and cyclic AMP response element binding protein phosphorylation via membrane receptors, providing evidence for a rapid nongenomic action of oestradiol in O. vulgaris. In the present study, we demonstrate, for the first time, the physiological role of oestradiol in the brain lobes of O. vulgaris involved in reproduction, learning and motor coordination. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  9. Insensitivity of Astrocytes to Interleukin-10 Signaling following Peripheral Immune Challenge Results in Prolonged Microglial Activation in the Aged Brain

    Science.gov (United States)

    Norden, Diana M.; Trojanowski, Paige J.; Walker, Frederick R.; Godbout, Jonathan P.

    2017-01-01

    Immune-activated microglia from aged mice produce exaggerated levels of cytokines. Despite high levels of microglial IL-10 in the aged brain, neuroinflammation was prolonged and associated with depressive-like deficits. Because astrocytes respond to IL-10 and, in turn, attenuate microglial activation, we investigated if astrocyte-mediated resolution of microglial activation was impaired with age. Here, aged astrocytes had a dysfunctional profile with higher GFAP, lower glutamate transporter expression, and significant cytoskeletal re-arrangement. Moreover, aged astrocytes had reduced expression of growth factors and IL-10 Receptor-1 (IL-10R1). Following in vivo LPS immune challenge, aged astrocytes had a molecular signature associated with reduced responsiveness to IL-10. This IL-10 insensitivity of aged astrocytes resulted in a failure to induce IL-10R1 and TGFβ and resolve microglial activation. Additionally, adult astrocytes reduced microglial activation when co-cultured ex vivo, while aged astrocytes did not. Consistent with the aging studies, IL-10RKO astrocytes did not augment TGFβ after immune challenge and failed to resolve microglial activation. Collectively, a major cytokine-regulatory loop between activated microglia and astrocytes is impaired in the aged brain. PMID:27318131

  10. Identification of Focal Epileptogenic Networks in Generalized Epilepsy Using Brain Functional Connectivity Analysis of Bilateral Intracranial EEG Signals.

    Science.gov (United States)

    Chen, Po-Ching; Castillo, Eduardo M; Baumgartner, James; Seo, Joo Hee; Korostenskaja, Milena; Lee, Ki Hyeong

    2016-09-01

    Simultaneous bilateral onset and bi-synchrony epileptiform discharges in electroencephalogram (EEG) remain hallmarks for generalized seizures. However, the possibility of an epileptogenic focus triggering rapidly generalized epileptiform discharges has been documented in several studies. Previously, a new multi-stage surgical procedure using bilateral intracranial EEG (iEEG) prior to and post complete corpus callosotomy (CC) was developed to uncover seizure focus in non-lateralizing focal epilepsy. Five patients with drug-resistant generalized epilepsy who underwent this procedure were included in the study. Their bilateral iEEG findings prior to complete CC showed generalized epileptiform discharges with no clear lateralization. Nonetheless, the bilateral ictal iEEG findings post complete CC indicated lateralized or localized seizure onset. This study hypothesized that brain functional connectivity analysis, applied to the pre CC bilateral iEEG recordings, could help identify focal epileptogenic networks in generalized epilepsy. The results indicated that despite diffuse epileptiform discharges, focal features can still be observed in apparent generalized seizures through brain connectivity analysis. The seizure onset localization/lateralization from connectivity analysis demonstrated a good agreement with the bilateral iEEG findings post complete CC and final surgical outcomes. Our study supports the role of focal epileptic networks in generalized seizures.

  11. Shadows of Music-Language Interaction on Low Frequency Brain Oscillatory Patterns

    Science.gov (United States)

    Carrus, Elisa; Koelsch, Stefan; Bhattacharya, Joydeep

    2011-01-01

    Electrophysiological studies investigating similarities between music and language perception have relied exclusively on the signal averaging technique, which does not adequately represent oscillatory aspects of electrical brain activity that are relevant for higher cognition. The current study investigated the patterns of brain oscillations…

  12. Signal Increase on Unenhanced T1-Weighted Images in the Rat Brain After Repeated, Extended Doses of Gadolinium-Based Contrast Agents

    Science.gov (United States)

    Jost, Gregor; Lenhard, Diana Constanze; Sieber, Martin Andrew; Lohrke, Jessica; Frenzel, Thomas; Pietsch, Hubertus

    2016-01-01

    Objectives In this prospective preclinical study, we evaluated T1-weighted signal intensity in the deep cerebellar nuclei (CN) and globus pallidus (GP) up to 24 days after repeated administration of linear and macrocyclic gadolinium-based contrast agents (GBCAs) using homologous imaging and evaluation methods as in the recently published retrospective clinical studies. In a second part of the study, cerebrospinal fluid (CSF) spaces were evaluated for contrast enhancement by fluid-attenuated magnetic resonance imaging (MRI). Materials and Methods Sixty adult male Wistar-Han rats were randomly divided into a control and 5 GBCA groups (n = 10 per group). The administered GBCAs were gadodiamide, gadopentetate dimeglumine, and gadobenate dimeglumine (linear GBCAs) as well as gadobutrol and gadoterate meglumine (macrocyclic GBCAs) and saline (control). Over a period of 2 weeks, the animals received 10 intravenous injections at a dose of 2.5 mmol Gd/kg body weight, each on 5 consecutive days per week. Before GBCA administration, as well as 3 and 24 days after the last injection, a whole-brain MRI was performed using a standard T1-weighted 3-dimensional turbo spin echo sequence on a clinical 1.5 T scanner. The ratios of signal intensities in deep CN to pons (CN/Po) and GP to thalamus (GP/Th) were determined. For the evaluation of the CSF spaces, 18 additional rats were randomly divided into 6 groups (n = 3 per group) that received the same GBCAs as in the first part of the study. After MR cisternography for anatomical reference, a fluid-attenuated inversion recovery sequence was performed before and 1 minute after intravenous injection of a dose of 1 mmol Gd/kg body weight GBCA or saline. Results A significantly increased signal intensity ratio of CN/Po was observed 3 and 24 days after the last injection of gadodiamide and gadobenate dimeglumine. No significant changes were observed between the 2 time points. Gadopentetate dimeglumine injection led to a moderately elevated

  13. Magnetic resonance signal intensity ratio of gray/white matter in children; Quantitative assessment in developing brain

    Energy Technology Data Exchange (ETDEWEB)

    Maezawa, Mariko (Tokyo Saiseikai Central Hospital (Japan)); Seki, Tohru; Imura, Soichi; Akiyama, Kazunori; Takikawa, Itsuro; Yuasa, Yuji

    Magnetic resonance imaging (MRI) findings in 87 children with various clinical entities were used to determine the signal intensity ratio of gray/white matter in T[sub 1]-weighted and T[sub 2]-weighted images using a 1.5 T MR scanner. Signal intensity ratio changes in both T[sub 1]- and T[sub 2]-weighted images correlated well with advancing age (y=0.9349-0.001575, r=0.584, P<0.0001 in T[sub 1]-weighted images; y=0.9798+0.002854, r=0.723, P<0.0001 in T[sub 2]-weighted images), but the correlation was more linear when we included only normally developed (34) children (y=0.9689-0.001967, r=-0.654, P<0.0001 in T[sub 1]-weighted images; y=0.9882+0.002965, r=0.747, P<0.0001 in T[sub 2]-weighted images). Abnormal ratios were observed in patients with congenital hydrocephalus, inherited metabolic diseases and cerebral palsy. Although the gray/white matter differentiation would not delineate the myelination itself, measurement of the signal intensity ratio of gray/white matters is a practical way to evaluate delayed myelination in a busy MR center. (author).

  14. Intravenous injection of gadobutrol in an epidemiological study group did not lead to a difference in relative signal intensities of certain brain structures after 5 years

    Energy Technology Data Exchange (ETDEWEB)

    Kromrey, Marie-Luise; Liedtke, Kim Rouven; Langner, Soenke; Kirsch, Michael; Kuehn, Jens-Peter [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); Ittermann, Till [University Medicine Greifswald, Institute for Community Medicine, Greifswald (Germany); Weitschies, Werner [University Greifswald, Institute of Biopharmacy and Pharmaceutical Technology, Greifswald (Germany)

    2017-02-15

    To investigate if application of macrocyclic gadolinium-based contrast agents in volunteers is associated with neuronal deposition detected by magnetic resonance imaging in a 5-year longitudinal survey. Three hundred eighty-seven volunteers who participated in a population-based study were enrolled. Subjects underwent plain T1-weighted brain MRI at baseline and 5 years later with identical sequence parameters. At baseline, 271 participants additionally received intravenous injection of the macrocyclic contrast agent gadobutrol (1.5 mmol/kg). A control group including 116 subjects received no contrast agent. Relative signal intensities of thalamus, pallidum, pons and dentate nucleus were compared at baseline and follow-up. No difference in relative signal intensities was observed between contrast group (thalamus, p = 0.865; pallidum, p = 0.263; pons, p = 0.533; dentate nucleus, p = 0.396) and control group (thalamus, p = 0.683; pallidum; p = 0.970; pons, p = 0.773; dentate nucleus, p = 0.232) at both times. Comparison between both groups revealed no significant differences in relative signal intensities (thalamus, p = 0.413; pallidum, p = 0.653; pons, p = 0.460; dentate nucleus, p = 0.751). The study showed no significant change in globus pallidus-to-thalamus or dentate nucleus-to-pons ratios. Five years after administration of a 1.5-fold dose gadobutrol to normal subjects, signal intensity of thalamus, pallidum, pons and dentate nucleus did not differ from participants who had not received gadobutrol. (orig.)

  15. Lactate doublet quantification and lipid signal suppression using a new biexponential decay filter: application to simulated and 1H MRS brain tumor time-domain data.

    Science.gov (United States)

    Serrai, Hacene; Senhadji, Lotfi; Wang, Guoyu; Akoka, Serge; Stroman, Patrick

    2003-09-01

    A new postprocessing filter based on the continuous wavelet transform (CWT) method modeled as a biexponential decay function to isolate the lactate doublet from overlapping lipid resonance(s) and estimate its magnetic resonance spectroscopy (MRS) parameters (signal amplitude, resonance frequencies, and apparent relaxation time (T(*) (2))) is proposed. The new filter employs the same iterative process used in the previously single exponential decay filter. A comparison of the results obtained from application of both filters to simulated data and real (1)H MRS data collected from human blood plasma and brain tumors demonstrates that the new filter provides a better estimate of MRS parameters of lactate, with less computation time. Furthermore, the results show that the new filter is less sensitive to noise and provides a direct estimate of J-coupling value of the lactate doublet. Copyright 2003 Wiley-Liss, Inc.

  16. Nonclassical Mechanisms of Progesterone Action in the Brain: II. Role of Calmodulin-Dependent Protein Kinase II in Progesterone-Mediated Signaling in the Hypothalamus of Female Rats

    Science.gov (United States)

    Balasubramanian, Bhuvana; Portillo, Wendy; Reyna, Andrea; Chen, Jian Zhong; Moore, Anthony N.; Dash, Pramod K.; Mani, Shaila K.

    2008-01-01

    In addition to the activation of classical progestin receptor-dependent genomic pathway, progesterone (P) can activate nonclassical, membrane-initiated signaling pathways in the brain. We recently demonstrated rapid P activation of second-messenger kinases, protein kinase A, and protein kinase C in the ventromedial nucleus (VMN) and preoptic area (POA) of rat brain. To determine whether P can activate yet another Ca+2dependent kinase, we examined the rapid P modulation of calcium and calmodulin-dependent protein kinase II (CaMKII) in the VMN and POA in female rats. A rapid P-initiated activation of CaMKII basal activity was observed in the VMN but not the POA at 30 min. Estradiol benzoate (EB) priming enhanced this CaMKII basal activity in both the VMN and POA. CaMKII protein levels and phosphorylation of Thr-286 moiety on CaMKII, however, remained unchanged with EB and/or P treatments, suggesting that the changes in the CaMKII kinase activity are due to rapid P modulation of the kinase activity and not its synthesis or autoactivation. Furthermore, intracerebroventricular (icv) administration of a CaMKII-specific inhibitor, KN-93, 30 min prior to the P infusion, in EB-primed, ovariectomized female rats inhibited CaMKII activation but not protein kinase A and protein kinase C activities. Interestingly, icv administration of KN-93 30 min prior to P infusion (icv) resulted in a reduction but not total inhibition of P-facilitated lordosis response in EB-primed female rats. These observations suggest a redundancy or, alternately, a hierarchy in the P-regulated activation of kinase signaling cascades in female reproductive behavior. PMID:18617607

  17. Angiotensin II-dependent hypertension requires cyclooxygenase 1-derived prostaglandin E2 and EP1 receptor signaling in the subfornical organ of the brain.

    Science.gov (United States)

    Cao, Xian; Peterson, Jeffrey R; Wang, Gang; Anrather, Josef; Young, Colin N; Guruju, Mallikarjuna R; Burmeister, Melissa A; Iadecola, Costantino; Davisson, Robin L

    2012-04-01

    Cyclooxygenase (COX)-derived prostanoids have long been implicated in blood pressure (BP) regulation. Recently prostaglandin E(2) (PGE(2)) and its receptor EP(1) (EP(1)R) have emerged as key players in angiotensin II (Ang II)-dependent hypertension (HTN) and related end-organ damage. However, the enzymatic source of PGE(2,) that is, COX-1 or COX-2, and its site(s) of action are not known. The subfornical organ (SFO) is a key forebrain region that mediates systemic Ang II-dependent HTN via reactive oxygen species (ROS). We tested the hypothesis that cross-talk between PGE(2)/EP(1)R and ROS signaling in the SFO is required for Ang II HTN. Radiotelemetric assessment of blood pressure revealed that HTN induced by infusion of systemic "slow-pressor" doses of Ang II was abolished in mice with null mutations in EP(1)R or COX-1 but not COX-2. Slow-pressor Ang II-evoked HTN and ROS formation in the SFO were prevented when the EP(1)R antagonist SC-51089 was infused directly into brains of wild-type mice, and Ang-II-induced ROS production was blunted in cells dissociated from SFO of EP(1)R(-/-) and COX-1(-/-) but not COX-2(-/-) mice. In addition, slow-pressor Ang II infusion caused a ≈3-fold increase in PGE(2) levels in the SFO but not in other brain regions. Finally, genetic reconstitution of EP(1)R selectively in the SFO of EP(1)R-null mice was sufficient to rescue slow-pressor Ang II-elicited HTN and ROS formation in the SFO of this model. Thus, COX 1-derived PGE(2) signaling through EP(1)R in the SFO is required for the ROS-mediated HTN induced by systemic infusion of Ang II and suggests that EP(1)R in the SFO may provide a novel target for antihypertensive therapy.

  18. HMGB1 regulates P-glycoprotein expression in status epilepticus rat brains via the RAGE/NF-κB signaling pathway

    Science.gov (United States)

    Xie, Yuan; Yu, Nian; Chen, Yan; Zhang, Kang; Ma, Hai-Yan; Di, Qing

    2017-01-01

    Overexpression of P-glycoprotein (P-gp) in the brain is an important mechanism involved in drug-resistant epilepsy (DRE). High-mobility group box 1 (HMGB1), an inflammatory cytokine, significantly increases following seizures and may be involved in upregulation of P-gp. However, the underlying mechanisms remain elusive. The aim of the present study was to evaluate the role of HMGB1 and its downstream signaling components, receptor for advanced glycation end-product (RAGE) and nuclear factor-κB (NF-κB), on P-gp expression in rat brains during status epilepticus (SE). Small interfering RNA (siRNA) was administered to rats prior to induction of SE by pilocarpine, to block transcription of the genes encoding HMGB1 and RAGE, respectively. An inhibitor of NF-κB, pyrrolidinedithiocarbamic acid (PDTC), was utilized to inhibit activation of NF-κB. The expression levels of HMGB1, RAGE, phosphorylated-NF-κB p65 (p-p65) and P-gp were detected by western blotting. The relative mRNA expression levels of the genes encoding these proteins were measured using reverse transcription-quantitative polymerase chain reaction and the cellular localization of the proteins was determined by immunofluorescence. Pre-treatment with HMGB1 siRNA reduced the expression levels of RAGE, p-p65 and P-gp. PDTC reduced the expression levels of P-gp. These findings suggested that overexpression of P-gp during seizures may be regulated by HMGB1 via the RAGE/NF-κB signaling pathway, and may be a novel target for treating DRE. PMID:28627626

  19. A comparison of three brain-computer interfaces based on event-related desynchronization, steady state visual evoked potentials, or a hybrid approach using both signals.

    Science.gov (United States)

    Brunner, C; Allison, B Z; Altstätter, C; Neuper, C

    2011-04-01

    Brain-computer interface (BCI) systems rely on the direct measurement of brain signals, such as event-related desynchronization (ERD), steady state visual evoked potentials (SSVEPs), P300s, or slow cortical potentials. Unfortunately, none of these BCI approaches work for all users. This study compares two conventional BCI approaches (ERD and SSVEP) within subjects, and also evaluates a novel hybrid BCI based on a combination of these signals. We recorded EEG data from 12 subjects across three conditions. In the first condition, subjects imagined moving both hands or both feet (ERD). In the second condition, subjects focused on one of the two oscillating visual stimuli (SSVEP). In the third condition, subjects simultaneously performed both tasks. We used logarithmic band power features at sites and frequencies consistent with ERD and SSVEP activity, and subjects received real-time feedback based on their performance. Subjects also completed brief questionnaires. All subjects could simultaneously perform the movement and visual task in the hybrid condition even though most subjects had little or no training. All subjects showed both SSVEP and ERD activity during the hybrid task, consistent with the activity in both single tasks. Subjects generally considered the hybrid condition moderately more difficult, but all of them were able to complete the hybrid task. Results support the hypothesis that subjects who do not have strong ERD activity might be more effective with an SSVEP BCI, and suggest that SSVEP BCIs work for more subjects. A simultaneous hybrid BCI is feasible, although the current hybrid approach, which involves combining ERD and SSVEP in a two-choice task to improve accuracy, is not significantly better than a comparable SSVEP BCI. Switching to an SSVEP BCI could increase reliability in subjects who have trouble producing the EEG activity necessary to use an ERD BCI. Subjects who are proficient in both BCI approaches might be able to combine these

  20. 17β-Estradiol via SIRT1/Acetyl-p53/NF-kB Signaling Pathway Rescued Postnatal Rat Brain Against Acute Ethanol Intoxication.

    Science.gov (United States)

    Khan, Mehtab; Shah, Shahid Ali; Kim, Myeong Ok

    2017-05-02

    Growing evidences reveal that 17β-estradiol has a wide variety of neuroprotective potential. Recently, it has been shown that 17β-estradiol can limit ethanol-induced neurotoxicity in neonatal rats. Whether it can stimulate SIRT1 signaling against ethanol intoxicity in developing brain remain elusive. Here, we report for the first time that 17β-estradiol activated SIRT1 to deacetylate p53 proteins against acute ethanol-induced oxidative stress, neuroinflammation, and neurodegeneration. A single subcutaneous injection of ethanol-induced oxidative stress triggered phospho c-jun N terminal kinase (p-JNK) and phospho mammalian target of rapamycin (p-mTOR) accompanied by neuroinflammation and widespread neurodegeneration. In contrast, 17β-estradiol cotreatment positively regulated SIRT1, inhibited p53 acetylation, reactive oxygen species (ROS) production, p-JNK, and p-mTOR activation and reduced neuroinflammation and neuronal cell death in the postnatal rat brain. Interestingly, SIRT1 inhibition with its inhibitor, i.e., EX527 further enhanced ethanol intoxication and also abolished the beneficial effects of 17β-estradiol against ethanol in the young rat's brain. Indeed, 17β-estradiol treatment increased the cell viability (HT22 cells), inhibited ROS production via the SIRT1/Acetyl-p53 pathway, and reduced the nuclear translocation of phospho-nuclear factor kappa B (p-NF-kB) in the BV2 microglia cells. Taken together, these results show that 17β-estradiol can be used as a potential neuroprotective agent against acute ethanol intoxication.

  1. Ginkgo biloba extract EGb761 attenuates brain death-induced renal injury by inhibiting pro-inflammatory cytokines and the SAPK and JAK-STAT signalings.

    Science.gov (United States)

    Li, Yifu; Xiong, Yunyi; Zhang, Huanxi; Li, Jun; Wang, Dong; Chen, Wenfang; Yuan, Xiaopeng; Su, Qiao; Li, Wenwen; Huang, Huiting; Bi, Zirong; Liu, Longshan; Wang, Changxi

    2017-03-23

    This study aimed to investigate the protective effects of EGb761, a Ginkgo Biloba extract, against brain death-induced kidney injury. Sixty male Sprague Dawley rats were randomly divided into six groups: sham, brain-death (BD), BD + EGb b48h (48 hours before BD), BD + EGb 2 h (2 hours after BD), BD + EGb 1 h, and BD + EGb 0.5 h. Six hours after BD, serum sample and kidney tissues were collected for analyses. The levels of blood urea nitrogen (BUN) and serum creatinine significantly elevated in the BD group than in sham group. In all the EGb761-treated BD animals except for the BD + Gb 2 h group, the levels of BUN and serum creatinine significantly reduced (all P < 0.01). EGb761 attenuated tubular injury and lowered the histological score. In addition, the longer duration of drug treatment was, the better protective efficacy could be observed. EGb761 significantly reduced IL-1β, IL-6, TNF-α, MCP-1, IP-10 mRNA expression and macrophage infiltration in the kidney. EGb761 treatment at 48 hour before brain death significantly attenuate the levels of p-JNK-MAPK, p-p38-MAPK, and p-STAT3 proteins (all P < 0.05, compared to BD group). In summary, our data showed that EGb761 treatment protected donor kidney from BD-induced damages by blocking SAPK and JAK-STAT signalings. Early administration of EGb761 can provide better protective efficacy.

  2. egr-4, a target of EGFR signaling, is required for the formation of the brain primordia and head regeneration in planarians.

    Science.gov (United States)

    Fraguas, Susanna; Barberán, Sara; Iglesias, Marta; Rodríguez-Esteban, Gustavo; Cebrià, Francesc

    2014-05-01

    During the regeneration of freshwater planarians, polarity and patterning programs play essential roles in determining whether a head or a tail regenerates at anterior or posterior-facing wounds. This decision is made very soon after amputation. The pivotal role of the Wnt/β-catenin and Hh signaling pathways in re-establishing anterior-posterior (AP) polarity has been well documented. However, the mechanisms that control the growth and differentiation of the blastema in accordance with its AP identity are less well understood. Previous studies have described a role of Smed-egfr-3, a planarian epidermal growth factor receptor, in blastema growth and differentiation. Here, we identify Smed-egr-4, a zinc-finger transcription factor belonging to the early growth response gene family, as a putative downstream target of Smed-egfr-3. Smed-egr-4 is mainly expressed in the central nervous system and its silencing inhibits anterior regeneration without affecting the regeneration of posterior regions. Single and combinatorial RNA interference to target different elements of the Wnt/β-catenin pathway, together with expression analysis of brain- and anterior-specific markers, revealed that Smed-egr-4: (1) is expressed in two phases - an early Smed-egfr-3-independent phase and a late Smed-egfr-3-dependent phase; (2) is necessary for the differentiation of the brain primordia in the early stages of regeneration; and (3) that it appears to antagonize the activity of the Wnt/β-catenin pathway to allow head regeneration. These results suggest that a conserved EGFR/egr pathway plays an important role in cell differentiation during planarian regeneration and indicate an association between early brain differentiation and the proper progression of head regeneration.

  3. Anthocyanin-rich açai (Euterpe oleracea Mart.) fruit pulp fractions attenuate inflammatory stress signaling in mouse brain BV-2 microglial cells.

    Science.gov (United States)

    Poulose, Shibu M; Fisher, Derek R; Larson, Jessica; Bielinski, Donna F; Rimando, Agnes M; Carey, Amanda N; Schauss, Alexander G; Shukitt-Hale, Barbara

    2012-02-01

    Age-related diseases of the brain compromise memory, learning, and movement and are directly linked with increases in oxidative stress and inflammation. Previous research has shown that supplementation with berries can modulate signaling in primary hippocampal neurons or BV-2 mouse microglial cells. Because of their high polyphenolic content, fruit pulp fractions of açai ( Euterpe oleracea Mart.) were explored for their protective effect on BV-2 mouse microglial cells. Freeze-dried açai pulp was fractionated using solvents with different polarities and analyzed using HPLC for major anthocyanins and other phenolics. Fractions extracted using methanol (MEOH) and ethanol (ETOH) were particularly rich in anthocyanins such as cyanidin, delphinidin, malvidin, pelargonidin, and peonidin, whereas the fraction extracted using acetone (ACE) was rich in other phenolics such as catechin, ferulic acid, quercetin, resveratrol, and synergic and vanillic acids. Studies were conducted to investigate the mitigating effects of açai pulp extracts on lipopolysaccharide (LPS, 100 ng/mL) induced oxidative stress and inflammation; treatment of BV-2 cells with acai fractions resulted in significant (p study offers valuable insights into the protective effects of açai pulp fractions on brain cells, which could have implications for improved cognitive and motor functions.

  4. Artificial rearing inhibits apoptotic cell death through action on pro-apoptotic signaling molecules during brain development: replacement licking partially reverses these effects.

    Science.gov (United States)

    Chatterjee-Chakraborty, Munmun; Chatterjee, Diptendu

    2010-08-12

    Early life stress associated with being reared without mother, siblings, and nest affects the formation of neuronal networks during rat development. Prior work shows that in comparison to mother-reared male rats, artificial rearing results in elevated numbers of neurons in adulthood and reduced apoptosis during the first postnatal week. Replacement with stroking stimulation, designed to simulate mothers' licking, reversed these effects in most brain areas. The present communication explored the effects of early rearing manipulations on signaling proteins. Male rats were reared until postnatal day 7 either in an artificial-feeding paradigm (AR) or with their mothers (MR). AR animals received different amounts of maternal-like stimulation using a soft paintbrush. Brains were extracted and prepared for molecular assays of 1) apoptosis and 2) pro and anti-apoptotic proteins on day 7 of postnatal life. Results showed that stimulation of the AR pups reversed the effects of artificial rearing on apoptosis in a dose dependent manner; low and very high levels of stimulation were without effect whereas moderate levels of stimulation produced effects on apoptosis similar to effects seen in mother-reared controls. Moreover, this artificial rearing effect and the pattern of reversal with stroking were also found for levels of pro-apoptotic Bax protein, the ratio of Bax/Bcl-2 and levels of activated caspase-3 which we believe mediates programmed cell death. Copyright 2010 Elsevier B.V. All rights reserved.

  5. Role of signal peptide-Cub-Egf domain-containing protein-1 in serum as a predictive biomarker of outcome after severe traumatic brain injury.

    Science.gov (United States)

    Chen, Qi-Han; Lin, Dan; Zhou, Jian; Deng, Gang

    2016-05-01

    Signal peptide-Cub-Epidermal growth factor domain-containing protein 1 (SCUBE1), a marker for coagulation, is secreted under hypoxia and inflammatory conditions from platelet α granules. This study was designed to determine the associations of serum SCUBE1 concentrations with trauma severity and prognosis after severe traumatic brain injury. Serum SCUBE1 concentrations of 113 patients and 113 controls were measured. An unfavorable outcome was defined as Glasgow Outcome Scale score of 1-3. Serum SCUBE1 concentrations were significantly higher in patients than in controls (15.5 ± 6.0 vs. 1.1 ± 0.3 ng/ml, P < 0.001) and were associated with Glasgow coma scale scores (r = -0.439, P < 0.001) and blood platelet count (r = 0.420, P < 0.001). SCUBE1 was identified as an independent prognostic marker of 6-month unfavorable outcome (odds ratio, 1.357; 95% confidence interval, 1.159-1.589; P < 0.001), and had high predictive value according to receiver operating characteristic curve (area under curve, 0.830; 95% confidence interval, 0.748-0.890; P < 0.001). Increased serum SCUBE1 concentrations are associated highly with trauma severity, platelet activation and poor outcome, suggesting that SCUBE1 might be a novel prognostic biomarker after traumatic brain injury. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. The effect of curcumin on the brain-gut axis in rat model of irritable bowel syndrome: involvement of 5-HT-dependent signaling.

    Science.gov (United States)

    Yu, Yingcong; Wu, Shujuan; Li, Jianxin; Wang, Renye; Xie, Xupei; Yu, Xuefeng; Pan, Jianchun; Xu, Ying; Zheng, Liang

    2015-02-01

    Irritable bowel syndrome (IBS) is induced by dysfunction of central nervous and peripheral intestinal systems, which affects an estimated 10-15% population worldwide annually. Stress-related psychiatric disorders including depression and anxiety are often comorbid with gastrointestinal function disorder, such as IBS. However, the mechanism of IBS still remains unknown. Curcumin is a biologically active phytochemical presents in turmeric and has pharmacological actions that benefit patients with depression and anxiety. Our study found that IBS rats showed depression- and anxiety-like behaviors associated with decreased 5-HT (serotonin), BDNF (Brain-derived neurotrophic factor) and pCREB (phosphorylation of cAMP response element-binding protein) expression in the hippocampus after chronic acute combining stress (CAS). However, these decreased parameters were obviously increased in the colonic after CAS. Curcumin (40 mg/kg) reduced the immobility time of forced swimming and the number of buried marbles in behavioral tests of CAS rats. Curcumin also decreased the number of fecal output and abdominal withdrawal reflex (AWR) scores in response to graded distention. Moreover, curcumin increased serotonin, BDNF and pCREB levels in the hippocampus, but they were decreased in the colonic of CAS rats. 5-HT(1A) receptor antagonist NAN-190 reversed the effects of curcumin on behaviors and the changes of intestine, pCREB and BDNF expression, which are related to IBS. These results suggested that curcumin exerts the effects on IBS through regulating neurotransmitters, BDNF and CREB signaling both in the brain and peripheral intestinal system.

  7. The effect of increased NaCl intake on rat brain endogenous μ-opioid receptor signaling.

    Science.gov (United States)

    Dadam, Florencia; Zádor, Ferenc; Caeiro, Ximena; Szűcs, Edina; Erdei, Anna I; Samavati, Reza; Gáspár, Róbert; Borsodi, Anna; Vivas, Laura

    2018-02-27

    Numerous studies demonstrate the significant role of central β-endorphin and its receptor, the μ-opioid receptor (MOR), in sodium intake regulation. The present study aimed to investigate the possible relationship between chronic high-NaCl intake and brain endogenous MOR functioning. We examined whether short-term (4 days) obligatory salt intake (2% NaCl solution) in rats may induce changes in MOR mRNA expression, G-protein activity and MOR binding capacity in brain regions involved in salt intake regulation. Plasma osmolality and electrolyte concentrations after sodium overload and the initial and final body weight of the animals were also examined. After 4 days of obligatory hypertonic sodium chloride intake, there was clearly no difference in MOR mRNA expression and G-protein activity in the median preoptic nucleus (MnPO). In the brainstem, MOR binding capacity also remained unaltered, but the maximal efficacy of MOR G-protein significantly increased. Finally, no significant alterations were observed in plasma osmolality and electrolyte concentrations. Interestingly, animals which received sodium gained significantly less weight than control animals. In conclusion, we found no significant alterations in the MnPO and brainstem in the number of available cell surface MORs or de novo syntheses of MOR after hypertonic sodium intake. The increased MOR G-protein activity following acute sodium overconsumption may participate in the maintenance of normal blood pressure levels and/or in enhancing sodium taste aversion and sodium overload-induced anorexia. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. Aripiprazole and Haloperidol Activate GSK3β-Dependent Signalling Pathway Differentially in Various Brain Regions of Rats

    Directory of Open Access Journals (Sweden)

    Bo Pan

    2016-03-01

    Full Text Available Aripiprazole, a dopamine D2 receptor (D2R partial agonist, possesses a unique clinical profile. Glycogen synthase kinase 3β (GSK3β-dependent signalling pathways have been implicated in the pathophysiology of schizophrenia and antipsychotic drug actions. The present study examined whether aripiprazole differentially affects the GSK3β-dependent signalling pathways in the prefrontal cortex (PFC, nucleus accumbens (NAc, and caudate putamen (CPu, in comparison with haloperidol (a D2R antagonist and bifeprunox (a D2R partial agonist. Rats were orally administrated aripiprazole (0.75 mg/kg, bifeprunox (0.8 mg/kg, haloperidol (0.1 mg/kg or vehicle three times per day for one week. The levels of protein kinase B (Akt, p-Akt, GSK3β, p-GSK3β, dishevelled (Dvl-3, and β-catenin were measured by Western Blots. Aripiprazole increased GSK3β phosphorylation in the PFC and NAc, respectively, while haloperidol elevated it in the NAc only. However, Akt activity was not changed by any of these drugs. Additionally, both aripiprazole and haloperidol, but not bifeprunox, increased the expression of Dvl-3 and β-catenin in the NAc. The present study suggests that activation of GSK3β phosphorylation in the PFC and NAc may be involved in the clinical profile of aripiprazole; additionally, aripiprazole can increase GSK3β phosphorylation via the Dvl-GSK3β-β-catenin signalling pathway in the NAc, probably due to its relatively low intrinsic activity at D2Rs.

  9. Brain derived neurotrophic factor is involved in the regulation of glycogen synthase kinase 3β (GSK3β) signalling

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Vivek, E-mail: vivek.gupta@mq.edu.au [Australian School of Advanced Medicine, Macquarie University (Australia); Chitranshi, Nitin; You, Yuyi [Australian School of Advanced Medicine, Macquarie University (Australia); Gupta, Veer [School of Medical Sciences, Edith Cowan University, Perth (Australia); Klistorner, Alexander; Graham, Stuart [Australian School of Advanced Medicine, Macquarie University (Australia); Save Sight Institute, Sydney University, Sydney (Australia)

    2014-11-21

    Highlights: • BDNF knockdown leads to activation of GSK3β in the neuronal cells. • BDNF knockdown can induce GSK3β activation beyond TrkB mediated effects. • BDNF impairment in vivo leads to age dependent activation of GSK3β in the retina. • Systemic treatment with TrkB agonist induces inhibition of retinal GSK3β. - Abstract: Glycogen synthase kinase 3β (GSK3β) is involved in several biochemical processes in neurons regulating cellular survival, gene expression, cell fate determination, metabolism and proliferation. GSK3β activity is inhibited through the phosphorylation of its Ser-9 residue. In this study we sought to investigate the role of BDNF/TrkB signalling in the modulation of GSK3β activity. BDNF/TrkB signalling regulates the GSK3β activity both in vivo in the retinal tissue as well as in the neuronal cells under culture conditions. We report here for the first time that BDNF can also regulate GSK3β activity independent of its effects through the TrkB receptor signalling. Knockdown of BDNF lead to a decline in GSK3β phosphorylation without having a detectable effect on the TrkB activity or its downstream effectors Akt and Erk1/2. Treatment with TrkB receptor agonist had a stimulating effect on the GSK3β phosphorylation, but the effect was significantly less pronounced in the cells in which BDNF was knocked down. The use of TrkB receptor antagonist similarly, manifested itself in the form of downregulation of GSK3β phosphorylation, but a combined TrkB inhibition and BDNF knockdown exhibited a much stronger negative effect. In vivo, we observed reduced levels of GSK3β phosphorylation in the retinal tissues of the BDNF{sup +/−} animals implicating critical role of BDNF in the regulation of the GSK3β activity. Concluding, BDNF/TrkB axis strongly regulates the GSK3β activity and BDNF also exhibits GSK3β regulatory effect independent of its actions through the TrkB receptor signalling.

  10. Assessing the user experience of older adults using a neural network trained to recognize emotions from brain signals.

    Science.gov (United States)

    Meza-Kubo, Victoria; Morán, Alberto L; Carrillo, Ivan; Galindo, Gilberto; García-Canseco, Eloisa

    2016-08-01

    The use of Ambient Assisted Living (AAL) technologies as a means to cope with problems that arise due to an increasing and aging population is becoming usual. AAL technologies are used to prevent, cure and improve the wellness and health conditions of the elderly. However, their adoption and use by older adults is still a major challenge. User Experience (UX) evaluations aim at aiding on this task, by identifying the experience that a user has while interacting with an AAL technology under particular conditions. This may help designing better products and improve user engagement and adoption of AAL solutions. However, evaluating the UX of AAL technologies is a difficult task, due to the inherent limitations of their subjects and of the evaluation methods. In this study, we validated the feasibility of assessing the UX of older adults while they use a cognitive stimulation application using a neural network trained to recognize pleasant and unpleasant emotions from electroencephalography (EEG) signals by contrasting our results with those of additional self-report and qualitative analysis UX evaluations. Our study results provide evidence about the feasibility of assessing the UX of older adults using a neural network that take as input the EEG signals; the classification accuracy of our neural network ranges from 60.87% to 82.61%. As future work we will conduct additional UX evaluation studies using the three different methods, in order to appropriately validate these results. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Determining optimal feature-combination for LDA classification of functional near-infrared spectroscopy signals in brain-computer interface application

    Directory of Open Access Journals (Sweden)

    Noman eNaseer

    2016-05-01

    Full Text Available In this study, we determine the optimal feature-combination for classification of functional near-infrared spectroscopy (fNIRS signals with the best accuracies for development of a two-class brain-computer interface (BCI. Using a multi-channel continuous-wave imaging system, mental arithmetic signals are acquired from the prefrontal cortex of seven healthy subjects. After removing physiological noises, six oxygenated and deoxygenated hemoglobin (HbO and HbR features — mean, slope, variance, peak, skewness and kurtosis — are calculated. All possible 2- and 3-feature combinations of the calculated features are then used to classify mental arithmetic versus rest using linear discriminant analysis (LDA. It is found that the combinations containing mean and peak values yielded significantly higher (p < 0.05 classification accuracies for both HbO and HbR than did all of the other combinations, across all of the subjects. These results demonstrate the feasibility of achieving high classification accuracies using mean and peak values of HbO and HbR as features for classification of mental arithmetic versus rest for a two-class BCI.

  12. Brain-derived neurotrophic factor signaling in the HVC is required for testosterone-induced song of female canaries.

    Science.gov (United States)

    Hartog, Tessa E; Dittrich, Falk; Pieneman, Anton W; Jansen, René F; Frankl-Vilches, Carolina; Lessmann, Volkmar; Lilliehook, Christina; Goldman, Steven A; Gahr, Manfred

    2009-12-09

    Testosterone-induced singing in songbirds is thought to involve testosterone-dependent morphological changes that include angiogenesis and neuronal recruitment into the HVC, a central part of the song control circuit. Previous work showed that testosterone induces the production of vascular endothelial growth factor (VEGF) and its receptor (VEGFR2 tyrosine kinase), which in turn leads to an upregulation of brain-derived neurotrophic factor (BDNF) production in HVC endothelial cells. Here we report for the first time that systemic inhibition of the VEGFR2 tyrosine kinase is sufficient to block testosterone-induced song in adult female canaries, despite sustained androgen exposure and the persistence of the effects of testosterone on HVC morphology. Expression of exogenous BDNF in HVC, induced locally by in situ transfection, reversed the VEGFR2 inhibition-mediated blockade of song development, thereby restoring the behavioral phenotype associated with androgen-induced song. The VEGFR2-inhibited, BDNF-treated females developed elaborate male-like song that included large syllable repertoires and high syllable repetition rates, features known to attract females. Importantly, although functionally competent new neurons were recruited to HVC after testosterone treatment, the time course of neuronal addition appeared to follow BDNF-induced song development. These findings indicate that testosterone-associated VEGFR2 activity is required for androgen-induced song in adult songbirds and that the behavioral effects of VEGFR2 inhibition can be rescued by BDNF within the adult HVC.

  13. Brain-Derived Neurotrophic Factor Signaling in the HVC Is Required for Testosterone-Induced Song of Female Canaries

    Science.gov (United States)

    Hartog, Tessa E.; Dittrich, Falk; Pieneman, Anton W.; Jansen, René F.; Frankl-Vilches, Carolina; Lessmann, Volkmar; Lilliehook, Christina; Goldman, Steven A.; Gahr, Manfred

    2012-01-01

    Testosterone-induced singing in songbirds is thought to involve testosterone-dependent morphological changes that include angiogenesis and neuronal recruitment into the HVC, a central part of the song control circuit. Previous work showed that testosterone induces the production of vascular endothelial growth factor (VEGF) and its receptor (VEGFR2 tyrosine kinase), which in turn leads to an upregulation of brain-derived neurotrophic factor (BDNF) production in HVC endothelial cells. Here we report for the first time that systemic inhibition of the VEGFR2 tyrosine kinase is sufficient to block testosterone-induced song in adult female canaries, despite sustained androgen exposure and the persistence of the effects of testosterone on HVC morphology. Expression of exogenous BDNF in HVC, induced locally by in situ transfection, reversed the VEGFR2 inhibition-mediated blockade of song development, thereby restoring the behavioral phenotype associated with androgen-induced song. The VEGFR2-inhibited, BDNF-treated females developed elaborate male-like song that included large syllable repertoires and high syllable repetition rates, features known to attract females. Importantly, although functionally competent new neurons were recruited to HVC after testosterone treatment, the time course of neuronal addition appeared to follow BDNF-induced song development. These findings indicate that testosterone-associated VEGFR2 activity is required for androgen-induced song in adult songbirds and that the behavioral effects of VEGFR2 inhibition can be rescued by BDNF within the adult HVC. PMID:20007475

  14. Heart – Brain Signaling in PFO Related Stroke: Differential Plasma Proteomic Expression Patterns Revealed with a Two-Pass LC-MS/MS Discovery Workflow

    Science.gov (United States)

    Lopez, Mary F; Sarracino, David A; Vogelsang, Maryann; Sutton, Jennifer N; Athanas, Michael; Krastins, Bryan; Garces, Alejandra; Prakash, Amol; Peterman, Scott; Demirjian, Zareh; Ignacio, Inglessis-Azuaje I; Feeney, Kathleen; Elia, Mikaela; McMullin, David; William Dec, G; Palacios, Igor; Lo, Eng H; Buonanno, Ferdinand; Ning, MingMing

    2013-01-01

    Patent foramen ovale (PFO) is highly prevalent and associated with more than 150,000 strokes per year. Traditionally, it is thought that PFOs facilitate strokes by allowing venous clots to travel directly to the brain. However, only a small portion of PFO stroke patients have a known tendency to form blood clots, and the best treatment for this multi-organ disease is unclear. Therefore, mapping the changes in systemic circulation of PFO-related stroke is crucial in understanding the pathophysiology in order to individualize the best clinical treatment for each patient. We initiated a study using a novel quantitative, Two-Pass discovery workflow using high-resolution LC-MS/MS coupled with label-free analysis to track protein expression in PFO patients before and after endovascular closure of the PFO. Using this approach, we were able to demonstrate quantitative differences in protein expression between both PFO-related and non PFO-related ischemic stroke groups as well as before and after PFO closure. As an initial step in understanding the molecular landscape of PFO-related physiology, our methods have yielded biologically relevant information on the synergistic and functional redundancy of various cell-signaling molecules with respect to PFO circulatory physiology. The resulting protein expression patterns were related to canonical pathways including prothrombin activation, atherosclerosis signaling, acute phase response, LXR/RXR activation and coagulation system. In particular, post PFO closure, numerous proteins demonstrated reduced expression in stroke-related canonical pathways such as acute inflammatory response and coagulation signaling. These findings demonstrate the feasibility and robustness of using a proteomic approach for biomarker discovery to help gauge therapeutic efficacy in stroke. PMID:23147404

  15. A Fully Integrated Wireless Compressed Sensing Neural Signal Acquisition System for Chronic Recording and Brain Machine Interface.

    Science.gov (United States)

    Liu, Xilin; Zhang, Milin; Xiong, Tao; Richardson, Andrew G; Lucas, Timothy H; Chin, Peter S; Etienne-Cummings, Ralph; Tran, Trac D; Van der Spiegel, Jan

    2016-07-18

    Reliable, multi-channel neural recording is critical to the neuroscience research and clinical treatment. However, most hardware development of fully integrated, multi-channel wireless neural recorders to-date, is still in the proof-of-concept stage. To be ready for practical use, the trade-offs between performance, power consumption, device size, robustness, and compatibility need to be carefully taken into account. This paper presents an optimized wireless compressed sensing neural signal recording system. The system takes advantages of both custom integrated circuits and universal compatible wireless solutions. The proposed system includes an implantable wireless system-on-chip (SoC) and an external wireless relay. The SoC integrates 16-channel low-noise neural amplifiers, programmable filters and gain stages, a SAR ADC, a real-time compressed sensing module, and a near field wireless power and data transmission link. The external relay integrates a 32 bit low-power microcontroller with Bluetooth 4.0 wireless module, a programming interface, and an inductive charging unit. The SoC achieves high signal recording quality with minimized power consumption, while reducing the risk of infection from through-skin connectors. The external relay maximizes the compatibility and programmability. The proposed compressed sensing module is highly configurable, featuring a SNDR of 9.78 dB with a compression ratio of 8×. The SoC has been fabricated in a 180 nm standard CMOS technology, occupying 2.1 mm × 0.6 mm silicon area. A pre-implantable system has been assembled to demonstrate the proposed paradigm. The developed system has been successfully used for long-term wireless neural recording in freely behaving rhesus monkey.

  16. Intestinal glucose-induced calcium-calmodulin kinase signaling in the gut-brain axis in awake rats.

    Science.gov (United States)

    Vincent, K M; Sharp, J W; Raybould, H E

    2011-07-01

    Lumenal glucose initiates changes in gastrointestinal (GI) function, including inhibition of gastric emptying, stimulation of pancreatic exocrine and endocrine secretion, and intestinal fluid secretion. Glucose stimulates the release of GI hormones and 5-hydroxytryptamine (5-HT), and activates intrinsic and extrinsic neuronal pathways to initiate changes in GI function. The precise mechanisms involved in luminal glucose-sensing are not clear; studying gut endocrine cells is difficult due to their sparse and irregular localization within the epithelium. Here we show a technique to determine activation of gut epithelial cells and the gut-brain pathway in vivo in rats using immunohistochemical detection of the activated, phosphorylated, form of calcium-calmodulin kinase II (pCaMKII). Perfusion of the gut with glucose (60 mg) increased pCaMKII immunoreactivity in 5-HT-expressing enterochromaffin (EC) cells, cytokeratin-18 immunopositive brush cells, but not in enterocytes or cholecystokinin-expressing cells. Lumenal glucose increased pCaMKII in neurons in the myenteric plexus and nodose ganglion, nucleus of the solitary tract, dorsal motor nucleus of the vagus and the arcuate nucleus. pCaMKII expression in neurons, but not in EC cells, was significantly attenuated by pretreatment with the 5-HT(3) R antagonist ondansetron. Deoxynojirimycin, a selective agonist for the putative glucose sensor, sodium-glucose cotransporter-3 (SGLT-3), mimicked the effects of glucose with increased pCaMKII in ECs and neurons; galactose had no effect. The data suggest that native EC cells in situ respond to glucose, possibly via SGLT-3, to activate intrinsic and extrinsic neurons and thereby regulate GI function. © 2011 Blackwell Publishing Ltd.

  17. Protective Effect of Klotho against Ischemic Brain Injury Is Associated with Inhibition of RIG-I/NF-κB Signaling

    Directory of Open Access Journals (Sweden)

    Hong-Jing Zhou

    2018-01-01

    Full Text Available Aging is the greatest independent risk factor for the occurrence of stroke and poor outcomes, at least partially through progressive increases in oxidative stress and inflammation with advanced age. Klotho is an antiaging gene, the expression of which declines with age. Klotho may protect against neuronal oxidative damage that is induced by glutamate. The present study investigated the effects of Klotho overexpression and knockdown by an intracerebroventricular injection of a lentiviral vector that encoded murine Klotho (LV-KL or rat Klotho short-hairpin RNA (LV-KL shRNA on cerebral ischemia injury and the underlying anti-neuroinflammatory mechanism. The overexpression of Klotho induced by LV-KL significantly improved neurobehavioral deficits and increased the number of live neurons in the hippocampal CA1 and caudate putamen subregions 72 h after cerebral hypoperfusion that was induced by transient bilateral common carotid artery occlusion (2VO in mice. The overexpression of Klotho significantly decreased the immunoreactivity of glial fibrillary acidic protein and ionized calcium binding adaptor molecule-1, the expression of retinoic-acid-inducible gene-I, the nuclear translocation of nuclear factor-κB, and the production of proinflammatory cytokines (tumor necrosis factor α and interleukin-6 in 2VO mice. The knockdown of Klotho mediated by LV-KL shRNA in the brain exacerbated neurological dysfunction and cerebral infarct after 22 h of reperfusion following 2 h middle cerebral artery occlusion in rats. These findings suggest that Klotho itself or enhancers of Klotho may compensate for its aging-related decline, thus providing a promising therapeutic approach for acute ischemic stroke during advanced age.

  18. Increased Airway Reactivity and Hyperinsulinemia in Obese Mice Are Linked by ERK Signaling in Brain Stem Cholinergic Neurons

    Directory of Open Access Journals (Sweden)

    Luiz O.S. Leiria

    2015-05-01

    Full Text Available Obesity is a major risk factor for asthma, which is characterized by airway hyperreactivity (AHR. In obesity-associated asthma, AHR may be regulated by non-TH2 mechanisms. We hypothesized that airway reactivity is regulated by insulin in the CNS, and that the high levels of insulin associated with obesity contribute to AHR. We found that intracerebroventricular (ICV-injected insulin increases airway reactivity in wild-type, but not in vesicle acetylcholine transporter knockdown (VAChT KDHOM−/−, mice. Either neutralization of central insulin or inhibition of extracellular signal-regulated kinases (ERK normalized airway reactivity in hyperinsulinemic obese mice. These effects were mediated by insulin in cholinergic nerves located at the dorsal motor nucleus of the vagus (DMV and nucleus ambiguus (NA, which convey parasympathetic outflow to the lungs. We propose that increased insulin-induced activation of ERK in parasympathetic pre-ganglionic nerves contributes to AHR in obese mice, suggesting a drug-treatable link between obesity and asthma.

  19. Initial Investigation into Microbleeds and White Matter Signal Changes following Radiotherapy for Low-Grade and Benign Brain Tumors Using Ultra-High-Field MRI Techniques.

    Science.gov (United States)

    Belliveau, J-G; Bauman, G S; Tay, K Y; Ho, D; Menon, R S

    2017-12-01

    External beam radiation therapy is a common treatment for many brain neoplasms. While external beam radiation therapy adheres to dose limits to protect the uninvolved brain, areas of high dose to normal tissue still occur. Patients treated with chemoradiotherapy can have adverse effects such as microbleeds and radiation necrosis, but few studies exist of patients treated without chemotherapy. Ten patients were treated for low-grade or benign neoplasms with external beam radiation therapy only and scanned within 12-36 months following treatment with a 7T MR imaging scanner. A multiecho gradient-echo sequence was acquired and postprocessed into SWI, quantitative susceptibility mapping, and apparent transverse relaxation maps. Six patients returned for follow-up imaging approximately 18 months following their first research scan and were imaged with the same techniques. At the first visit, 7/10 patients had microbleeds evident on SWI, quantitative susceptibility mapping, and apparent transverse relaxation. All microbleeds were within a dose region of >45 Gy. Additionally, 4/10 patients had asymptomatic WM signal changes evident on standard imaging. Further analysis with our technique revealed that these lesions were venocentric, suggestive of a neuroinflammatory process. There exists a potential for microbleeds in patients treated with external beam radiation therapy without chemotherapy. This finding is of clinical relevance because it could be a precursor of future neurovascular disease and indicates that additional care should be taken when using therapies such as anticoagulants. Additionally, the appearance of venocentric WM lesions could be suggestive of a neuroinflammatory mechanism that has been suggested in diseases such as MS. Both findings merit further investigation in a larger population set. © 2017 by American Journal of Neuroradiology.

  20. Environmental contributors to modulation of brain estrogen signaling and male gender bias in autism: A reply to the oral contraceptive use hypothesis by Strifert (2015).

    Science.gov (United States)

    Fluegge, Keith

    2017-07-01

    Strifert has recently put forward an interesting hypothesis regarding the role of oral contraceptive (OC) use in mothers and risk of offspring autism spectrum disorder (ASD). First, the author reports that combined oral contraceptives (COCs), containing both estrogen and progesterone, were developed in the late 1950s and early 60s, which is a time-frame distinct from Leo Kanner's documentation of infantile ASD in 1943 that Strifert just briefly mentions. While this important temporal inconsistency of ASD origin does not invalidate the potential role of OC use in contributing to the rise of ASD, it does support the likely possibility of other environmental exposures at play. Second, the epigenetic basis of the hypothesis is that the endocrine-disrupting components (i.e., ethinylestradiol) of OC perturb estrogenic signaling in the fetal brain by triggering aberrant DNA methylation of the estrogen receptor β (ERβ) gene, and such methylation patterns may be imprinted to future generations and could theoretically increase subsequent ASD offspring risk. The premise of the hypothesis is challenged, however, with the recognition that MeCP2, a "reader" of DNA methylation sites, is not only associated with age-dependent alteration in ERβ in females but is also significantly reduced in ASD brain. Furthermore, Strifert does not clearly address how the OC hypothesis accounts for the male bias in ASD. Therefore, the purpose of this correspondence is to address these inconsistencies by proposing a hypothesis that challenges these points. That is, gestational exposure to the agricultural and combustion air pollutant, nitrous oxide (N2O), may be a leading contributor to the development of an ASD phenotype. The mechanism undergirding this hypothesis suggests that compensatory estrogenic activity may mitigate the effects of fetal N2O exposure and thereby confer a protective effect against ASD development in a sex-dependent manner (i.e., male bias in ASD). Copyright © 2017

  1. Ultrasound Enhances the Expression of Brain-Derived Neurotrophic Factor in Astrocyte Through Activation of TrkB-Akt and Calcium-CaMK Signaling Pathways.

    Science.gov (United States)

    Liu, Shing-Hwa; Lai, Yi-Long; Chen, Bo-Lin; Yang, Feng-Yi

    2017-06-01

    Low-intensity pulsed ultrasound (LIPUS) stimulation has been shown to increase the expression of brain-derived neurotrophic factor (BDNF) in astrocytes of an in vitro model and rat brains of an in vivo model; however, their molecular mechanisms are still not well clarified. Here, we investigated the underlying mechanisms of BDNF enhancement by LIPUS in rat cerebral cortex astrocytes. After LIPUS stimulation in astrocytes, the protein and mRNA expressions were measured by western blot and RT-PCR, respectively. The concentration of intracellular calcium was determined spectrophotometrically. The results showed that LIPUS enhanced the phosphorylation of tropomyosin-related kinase B (TrkB) and Akt but had no effect on Erk1/2 phosphorylation. Additionally, LIPUS increased the intracellular concentration of calcium and enhanced the protein levels of calmodulin-dependent kinase (CaMK) II and CaMKIV. LIPUS also activated the phosphorylation of NF-κB-p65 but did not promote the activation of cAMP response element-binding protein (CREB). Taken together, our results suggest that LIPUS stimulation upregulates BDNF production in astrocytes through the activation of NF-κB via the TrkB/PI3K/Akt and calcium/CaMK signaling pathways. BDNF has emerged as a major molecular player in the regulation of neural circuit development and function. Therefore, LIPUS stimulation may play a crucial and beneficial role in neurodegenerative diseases. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Vigilance task-related change in brain functional connectivity as revealed by wavelet phase coherence analysis of near-infrared spectroscopy signals

    Directory of Open Access Journals (Sweden)

    Wang Wei

    2016-08-01

    Full Text Available This study aims to assess the vigilance task-related change in connectivity in healthy adults using wavelet phase coherence (WPCO analysis of near-infrared spectroscopy signals (NIRS. NIRS is a non-invasive neuroimaging technique for assessing brain activity. Continuous recordings of the NIRS signals were obtained from the prefrontal cortex (PFC and sensorimotor cortical areas of 20 young healthy adults (24.9±3.3 years during a 10-min resting state and a 20-min vigilance task state. The vigilance task was used to simulate driving mental load by judging three random numbers (i.e., whether odd numbers. The task was divided into two sessions: the first 10 minutes (Task t1 and the second 10 minutes (Task t2. The WPCO of six channel pairs were calculated in five frequency intervals: 0.6–2 Hz (I, 0.145–0.6 Hz (II, 0.052–0.145 Hz (III, 0.021–0.052 Hz (IV, and 0.0095–0.021 Hz (V. The significant WPCO formed global connectivity (GC maps in intervals I and II and functional connectivity (FC maps in intervals III to V. Results show that the GC levels in interval I and FC levels in interval III were significantly lower in the Task t2 than in the resting state (p < 0.05, particularly between the left PFC and bilateral sensorimotor regions. Also, the reaction time shows an increase in Task t2 compared with that in Task t1. However, no significant difference in WPCO was found between Task t1 and resting state. The results showed that the change in FC at the range of 0.6-2 Hz was not attributed to the vigilance task pe se, but the interaction effect of vigilance task and time factors. The findings suggest that the decreased attention level might be partly attributed to the reduced GC levels between the left prefrontal region and sensorimotor area. The present results provide a new insight into the vigilance task-related brain activity.

  3. Angiotensin-II-dependent Hypertension Requires Cyclooxygenase 1-derived Prostaglandin E2 and EP1 Receptor Signaling in the Subfornical Organ of the Brain

    Science.gov (United States)

    Cao, Xian; Peterson, Jeffrey R.; Wang, Gang; Anrather, Josef; Young, Colin N.; Guruju, Mallikarjuna R.; Burmeister, Melissa A.; Iadecola, Costantino; Davisson, Robin L.

    2012-01-01

    Cyclooxygenase (COX)-derived prostanoids have long been implicated in blood pressure (BP) regulation. Recently prostaglandin E2 (PGE2) and its receptor EP1R have emerged as key players in angiotensin II (Ang-II)-dependent hypertension (HTN) and related end-organ damage. However, the enzymatic source of PGE2, ie COX-1 or COX-2, and its site(s) of action are not known. The subfornical organ (SFO) is a key forebrain region that mediates systemic Ang-II-dependent HTN via reactive oxygen species (ROS). We tested the hypothesis that cross-talk between PGE2/EP1R and ROS signaling in the SFO is required for Ang-II HTN. Radiotelemetric assessment of BP revealed that HTN induced by infusion of systemic “slow-pressor” doses of Ang-II was abolished in mice with null mutations in EP1R or COX-1 but not COX-2. Slow-pressor Ang-II-evoked HTN and ROS formation in the SFO were prevented when the EP1R antagonist SC-51089 was infused directly into brains of wild-type mice, and Ang-II-induced ROS production was blunted in cells dissociated from SFO of EP1R−/− and COX-1−/− but not COX-2−/− mice. In addition, slow-pressor Ang-II infusion caused a ~3-fold increase in PGE2 levels in the SFO but not in other brain regions. Finally, genetic reconstitution of EP1R selectively in the SFO of EP1R-null mice was sufficient to rescue slow-pressor AngII-elicited HTN and ROS formation in the SFO of this model. Thus, COX-1-derived PGE2 signaling through EP1R in the SFO is required for the ROS-mediated HTN induced by systemic infusion of Ang-II, and suggests that EP1R in the SFO may provide a novel target for antihypertensive therapy. PMID:22371360

  4. Tensor decomposition of EEG signals: A brief review

    OpenAIRE

    Cong, Fengyu; Lin, Qiu-Hua; Kuang, Li-Dan; Gong, Xiao-Feng; Astikainen, Piia; Ristaniemi, Tapani

    2015-01-01

    Electroencephalography (EEG) is one fundamental tool for functional brain imaging. EEG signals tend to be represented by a vector or a matrix to facilitate data processing and analysis with generally understood methodologies like time-series analysis, spectral analysis and matrix decomposition. Indeed, EEG signals are often naturally born with more than two modes of time and space, and they can be denoted by a multi-way array called as tensor. This review summarizes the current pr...

  5. Joint Maximum Likelihood Time Delay Estimation of Unknown Event-Related Potential Signals for EEG Sensor Signal Quality Enhancement

    Directory of Open Access Journals (Sweden)

    Kyungsoo Kim

    2016-06-01

    Full Text Available Electroencephalograms (EEGs measure a brain signal that contains abundant information about the human brain function and health. For this reason, recent clinical brain research and brain computer interface (BCI studies use EEG signals in many applications. Due to the significant noise in EEG traces, signal processing to enhance the signal to noise power ratio (SNR is necessary for EEG analysis, especially for non-invasive EEG. A typical method to improve the SNR is averaging many trials of event related potential (ERP signal that represents a brain’s response to a particular stimulus or a task. The averaging, however, is very sensitive to variable delays. In this study, we propose two time delay estimation (TDE schemes based on a joint maximum likelihood (ML criterion to compensate the uncertain delays which may be different in each trial. We evaluate the performance for different types of signals such as random, deterministic, and real EEG signals. The results show that the proposed schemes provide better performance than other conventional schemes employing averaged signal as a reference, e.g., up to 4 dB gain at the expected delay error of 10°.

  6. Recording of brain activity across spatial scales

    NARCIS (Netherlands)

    Lewis, C.M.; Bosman, C.A.; Fries, P.

    2015-01-01

    Brain activity reveals exquisite coordination across spatial scales, from local microcircuits to brain-wide networks. Understanding how the brain represents, transforms and communicates information requires simultaneous recordings from distributed nodes of whole brain networks with single-cell

  7. Comparative Analysis of Signal Intensity and Apparent Diffusion Coefficient at Varying b-values in the Brain : Diffusion Weighted-Echo Planar Image (T{sub 2} and FLAIR) Sequence

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jong Kap [Dept. of Radiology, Cheomdan Medical Center, Gwangju (Korea, Republic of); Im, Jung Yeol [Dept. of Digital Management Information Graduate School of Nambu Univesity, Gwangju (Korea, Republic of)

    2009-09-15

    Diffusion-weighted imaging (DWI) has been demonstrated to be a practical method for the diagnosis of various brain diseases such as acute infarction, brain tumor, and white matter disease. In this study, we used two techniques to examine the average signal intensity (SI) and apparent diffusion coefficient (ADC) of the brains of patients who ranged in age from 10 to 60 years. Our results indicated that the average SI was the highest in amygdala (as derived from DWI), whereas that in the cerebrospinal fluid was the lowest. The average ADC was the highest in the cerebrospinal fluid, whereas the lowest measurement was derived from the pons. The average SI and ADC were higher in T{sub 2}-DW-EPI than in FLAIR-DW-EPI. The higher the b-value, the smaller the average difference in both imaging techniques; the lower the b-value, the greater the average difference. Also, comparative analysis of the brains of patients who had experienced cerebral infarction showed no distinct lesion in the general MR image over time. However, there was a high SI in apparent weighted images. Analysis of other brain diseases (e.g., bleeding, acute, subacute, chronic infarction) indicated SI variance in accordance with characteristics of the two techniques. The higher the SI, the lower the ADC. Taken together, the value of SI and ADC in accordance with frequently occurring areas and various brain disease varies based on the b-value and imaging technique. Because they provide additional useful information in the diagnosis and treatment of patients with various brain diseases through signal recognition, the proper imaging technique and b-value are important for the detection and interpretation of subacute stroke and other brain diseases.

  8. Magnetic nanoparticles: an emerging technology for malignant brain tumor imaging and therapy

    Science.gov (United States)

    Wankhede, Mamta; Bouras, Alexandros; Kaluzova, Milota; Hadjipanayis, Costas G

    2012-01-01

    Magnetic nanoparticles (MNPs) represent a promising nanomaterial for the targeted therapy and imaging of malignant brain tumors. Conjugation of peptides or antibodies to the surface of MNPs allows direct targeting of the tumor cell surface and potential disruption of active signaling pathways present in tumor cells. Delivery of nanoparticles to malignant brain tumors represents a formidable challenge due to the presence of the blood–brain barrier and infiltrating cancer cells in the normal brain. Newer strategies permit better delivery of MNPs systemically and by direct convection-enhanced delivery to the brain. Completion of a human clinical trial involving direct injection of MNPs into recurrent malignant brain tumors for thermotherapy has established their feasibility, safety and efficacy in patients. Future translational studies are in progress to understand the promising impact of MNPs in the treatment of malignant brain tumors. PMID:22390560

  9. Relationship between amplitude of resting-state fNIRS global signal and EEG vigilance measures.

    Science.gov (United States)

    Yuxuan Chen; Farrand, Jesse; Tang, Julia; Yafen Chen; O'Keeffe, Johnny; Guofa Shou; Lei Ding; Han Yuan

    2017-07-01

    Most of the prior studies of functional connectivity in both healthy and diseased brain utilized resting-state functional magnetic resonance imaging (fMRI) as a measure to represent the temporal synchrony in blood oxygenation level dependent (BOLD) signals across brain regions. To eliminate the impact of widely distributed global signal component across the brain, many studies have adopted global signal regression (GSR) as a pre-processing approach to regress the global signal component out of BOLD signals followed by computing hemodynamic connectivity. However, the procedure of global signal regression has been debated as physiologically relevant component may be present in global signal. In this study, we aimed to address the controversy of global signal using functional non-invasive neuroimaging technology, i.e. functional near-infrared spectroscopy (fNIRS), which measures hemodynamic signals by probing local changes in oxygen consumption, a common imaging contrast measured by BOLD fMRI. In the current study, we acquired simultaneous EEG and fNIRS signals, both in high-density configuration and whole-brain coverage, in healthy individuals at eyes-open and eyes-closed resting state and at three different body positions. We explored the underlying relationship between fNIRS global signal and EEG vigilance, and have identified negative correlation between fNIRS global signal and EEG vigilance across the physiological variations of measurements.

  10. Type A and B monoamine oxidases distinctly modulate signal transduction pathway and gene expression to regulate brain function and survival of neurons.

    Science.gov (United States)

    Naoi, Makoto; Maruyama, Wakako; Shamoto-Nagai, Masayo

    2017-12-26

    Type A and B monoamine oxidases (MAO-A, -B) mediate and modulate intracellular signal pathways for survival or death of neuronal cells. MAO-A is associated with development of neuronal architecture, synaptic activity, and onset of psychiatric disorders, including depression, and antisocial aggressive impulsive behaviors. MAO-B produces hydrogen peroxide and plays a vital role in neuronal loss of neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases. This review presents a novel role of MAO-A and B, their substrates and inhibitors, and hydrogen peroxide in brain function and neuronal survival and death. MAO-A activity is regulated not only by genetic factor, but also by environmental factors, including stress, hormonal deregulation, and food factors. MAO-A activity fluctuates by genetic-environmental factors, modulates the neuronal response to the stimuli, and affects behavior and emotional activities. MAO-B inhibitors selegiline and rasagiline protect neurons via increase expression of anti-apoptotic Bcl-2 and pro-survival neurotrophic factors in human neuroblastoma SH-SY5Y and glioblastoma U118MG cell lines. MAO-A knockdown suppressed the rasagiline-induced gene expression in SH-SY5Y cells, whereas MAO-B silencing enhanced the basal- and selegiline-induced gene expression in U118MG cells. MAO-A and B were shown to function as a mediator or repressor of gene expression, respectively. Further study on cellular mechanism underlying regulation of signal pathways by MAO-A and B may bring us a new insight on the role of MAOs in decision of neuronal fate and the development of novel therapeutic strategy may be expected for neuropsychiatric disorders.

  11. Co-Treatment with Anthocyanins and Vitamin C Ameliorates Ethanol- Induced Neurodegeneration via Modulation of GABAB Receptor Signaling in the Adult Rat Brain.

    Science.gov (United States)

    Badshah, Haroon; Ali, Tahir; Ahmad, Ashfaq; Kim, Min J; Abid, Noman Bin; Shah, Shahid A; Yoon, Gwang H; Lee, Hae Y; Kim, Myeong O

    2015-01-01

    Chronic ethanol exposure is known to cause neuronal damage in both humans and experimental animal models. Ethanol treatment induces neurotoxicity via the generation of reactive oxygen species (ROS), while anthocyanins (extracted from black soybean) and ascorbic acid (vitamin C) are free radical scavengers that can be used as neuroprotective agents against ROS. In this study the underlying neuroprotective potential of black soybean anthocyanins and vitamin C was determined. For this purpose, adult rats were exposed to 10% (v/v) ethanol for 8 weeks, followed by co-treatment with anthocyanins (24 mg/kg) and vitamin C (100 mg/kg) during the last 4 weeks. Our results showed that ethanol administration increased the expression of γ -aminobutyric acid B1 receptor (GABAB1R) and induced neuronal apoptosis via alterations to the Bax/Bcl-2 ratio, release of cytochrome C and activation of caspase-3 and caspase-9. Anthocyanins alone and supplementation with vitamin C showed an additive effect in reversing the trend of apoptotic signals induced by ethanol in the cortex and hippocampus. Consequently, anthocyanins also decreased the expression of poly (ADP ribose) polymerase-1 induced by ethanol and prevented DNA damage. Furthermore, anthocyanins and vitamin C reversed the ethanol-induced expression of GABAB1R and its downstream signaling molecule phospho-cAMP response element binding protein. Moreover, histopathology and immunohistochemistry results showed that anthocyanins and vitamin C significantly reduced ethanol-induced neuronal cell death. Our study revealed a neuroprotective role of anthocyanins and vitamin C via modulation of GABAB1R expression in the adult brain. Hence, we suggest that anthocyanins or co-treatment with anthocyanins and vitamin C may be a new and potentially effective neuroprotective agent for alcohol abuse.

  12. REGULATION OF BLOOD PRESSURE, APPETITE AND GLUCOSE BY LEPTIN AFTER INACTIVATION OF INSULIN RECEPTOR SUBSTRATE 2 (IRS2) SIGNALING IN THE ENTIRE BRAIN OR IN POMC NEURONS

    Science.gov (United States)

    do Carmo, Jussara M.; da Silva, Alexandre A.; Wang, Zhen; Freeman, Nathan J.; Alsheik, Ammar J.; Adi, Ahmad; Hall, John E.

    2016-01-01

    Insulin receptor substrate 2 (IRS2) is one of three major leptin receptor signaling pathways, but its role in mediating the chronic effects of leptin on blood pressure, food intake and glucose regulation is unclear. We tested if genetic inactivation of IRS2 in the entire brain (IRS2/Nestin-cre mice) or specifically in proopiomelanocortin (POMC) neurons (IRS2/POMC-cre mice) attenuates the chronic cardiovascular, metabolic and antidiabetic effects of leptin. Mice were instrumented with telemetry probes for measurement of blood pressure (BP) and heart rate (HR) and with venous catheters for intravenous infusions. After a 5-day control period, mice received leptin infusion (2 µg/kg/min) for 7 days. Compared to control IRS2flox/flox mice, IRS2/POMC-cre mice had similar body weight and food intake (33±1 vs. 35±1g and 3.6±0.5 vs. 3.8±0.2 g/day) but higher MAP and HR (110±2 vs. 102±2 mmHg and 641±9 vs. 616±5 bpm). IRS2/Nestin-cre mice were heavier (38±2 g), slightly hyperphagic (4.5±1.0 g/day), and had higher MAP and HR (108±2 mmHg and 659±9 bpm) compared to control mice. Leptin infusion gradually increased MAP despite decreasing food intake by 31% in IRS2flox/flox as well as in Nestin-cre control mice. In contrast, leptin infusion did not change MAP in IRS2/Nestin-cre or IRS2/POMC-cre mice. The anorexic and antidiabetic effects of leptin, however, were similar in all 3 groups. These results indicate that IRS2 signaling in the CNS, and particularly in POMC neurons, is essential for the chronic actions of leptin to raise MAP but not for its anorexic or antidiabetic effects. PMID:26628674

  13. Brain-derived neurotrophic factor (BDNF)-induced tropomyosin-related kinase B (Trk B) signaling is a potential therapeutic target for peritoneal carcinomatosis arising from colorectal cancer.

    Science.gov (United States)

    Tanaka, Koji; Okugawa, Yoshinaga; Toiyama, Yuji; Inoue, Yasuhiro; Saigusa, Susumu; Kawamura, Mikio; Araki, Toshimitsu; Uchida, Keiichi; Mohri, Yasuhiko; Kusunoki, Masato

    2014-01-01

    Tropomyosin-related receptor kinase B (TrkB) signaling, stimulated by brain-derived neurotrophic factor (BDNF) ligand, promotes tumor progression, and is related to the poor prognosis of various malignancies. We sought to examine the clinical relevance of BDNF/TrkB expression in colorectal cancer (CRC) tissues, its prognostic value for CRC patients, and its therapeutic potential in vitro and in vivo. Two hundred and twenty-three CRC patient specimens were used to determine both BDNF and TrkB mRNA levels. The expression of these proteins in their primary and metastatic tumors was investigated by immunohistochemistry. CRC cell lines and recombinant BDNF and K252a (a selective pharmacological pan-Trk inhibitor) were used for in vitro cell viability, migration, invasion, anoikis resistance and in vivo peritoneal metastasis assays. Tissue BDNF mRNA was associated with liver and peritoneal metastasis. Tissue TrkB mRNA was also associated with lymph node metastasis. The co-expression of BDNF and TrkB was associated with liver and peritoneal metastasis. Patients with higher BDNF, TrkB, and co-expression of BDNF and TrkB had a significantly poor prognosis. BDNF increased tumor cell viability, migration, invasion and inhibited anoikis in the TrkB-expressing CRC cell lines. These effects were suppressed by K252a. In mice injected