Open Access Published by De Gruyter Open Access

Volume 4 Issue 3

September 2013

Issue of Translational Neuroscience

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Contents
Journal Overview

Open Access September 13, 2013

The brake within: Mechanisms of intrinsic regulation of axon growth featuring the Cdh1-APC pathway

Judith Stegmüller

Page range: 273-281

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Abstract

Neurons of the central nervous system (CNS) form a magnificent network destined to control bodily functions and human behavior for a lifetime. During development of the CNS, neurons extend axons that establish connections to other neurons. Axon growth is guided by extrinsic cues and guidance molecules. In addition to environmental signals, intrinsic programs including transcription and the ubiquitin proteasome system (UPS) have been implicated in axon growth regulation. Over the past few years it has become evident that the E3 ubiquitin ligase Cdh1-APC together with its associated pathway plays a central role in axon growth suppression. By elucidating the intricate interplay of extrinsic and intrinsic mechanisms, we can enhance our understanding of why axonal regeneration in the CNS fails and obtain further insight into how to stimulate successful regeneration after injury.

Open Access September 13, 2013

Towards dynamical network biomarkers in neuromodulation of episodic migraine

Markus Dahlem, Sebastian Rode, Arne May, Naoya Fujiwara, Yoshito Hirata, Kazuyuki Aihara, Jürgen Kurths

Page range: 282-294

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Abstract

Computational methods have complemented experimental and clinical neurosciences and led to improvements in our understanding of the nervous systems in health and disease. In parallel, neuromodulation in form of electric and magnetic stimulation is gaining increasing acceptance in chronic and intractable diseases. In this paper, we firstly explore the relevant state of the art in fusion of both developments towards translational computational neuroscience. Then, we propose a strategy to employ the new theoretical concept of dynamical network biomarkers (DNB) in episodic manifestations of chronic disorders. In particular, as a first example, we introduce the use of computational models in migraine and illustrate on the basis of this example the potential of DNB as early-warning signals for neuromodulation in episodic migraine.

Open Access September 13, 2013

Protective effect of tea polyphenols on the blood-brain barrier

Rongliang Xue, Jianrui Lv, Jing Gao, Rongguo Fu, Wei Li, Xiaoming Lei, Gang Wu, Li Xue, Zhenni Zhang

Page range: 295-301

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Abstract

This study was to investigate the protective effects of tea polyphenols on the blood-brain barrier (BBB) of rats with global cerebral ischemia/reperfusion (GCIR) injury. Sprague Dawley rats underwent four-vessel occlusion to construct the model of GCIR. Half an hour before complete occlusion, they were treated with tea polyphenols (TP) (6.4%; 100 or 200 mg/kg) via tail intravenous injection. 24 h after reperfusion, BBB permeability was evaluated by measuring brain water content (BWC) and residual amount of Evan’s blue dye in cerebral tissue. In addition to this, MMP-9 and collagen IV protein expression in cerebral tissue were also detected using immunohistochemistry. ANOVA and SNK-q were used to do statistical analysis. Statistical significance was considered at P<0.05. Compared to the untreated, the TP-treated rats had significantly decreased BWC (P<0.05), decreased residual amount of Evan’s blue dye in cerebral tissue (P<0.05), down-regulated MMP-9 (P<0.05) and up-regulated collagen IV expression in brain tissue (P<0.05). It can be concluded from these findings that TP may reduce the MMP-9 mediated collagen IV degradation caused by GCIR to protect the BBB.

Open Access September 13, 2013

Breath-hold diving as a brain survival response

Zeljko Dujic, Toni Breskovic, Darija Bakovic

Page range: 302-313

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Abstract

Elite breath-hold divers are unique athletes challenged with compression induced by hydrostatic pressure and extreme hypoxia/hypercapnia during maximal field dives. The current world records for men are 214 meters for depth (Herbert Nitsch, No-Limits Apnea discipline), 11:35 minutes for duration (Stephane Mifsud, Static Apnea discipline), and 281 meters for distance (Goran Čolak, Dynamic Apnea with Fins discipline). The major physiological adaptations that allow breath-hold divers to achieve such depths and duration are called the “diving response” that is comprised of peripheral vasoconstriction and increased blood pressure, bradycardia, decreased cardiac output, increased cerebral and myocardial blood flow, splenic contraction, and preserved O2 delivery to the brain and heart. This complex of physiological adaptations is not unique to humans, but can be found in all diving mammals. Despite these profound physiological adaptations, divers may frequently show hypoxic loss of consciousness. The breath-hold starts with an easy-going phase in which respiratory muscles are inactive, whereas during the second so-called “struggle” phase, involuntary breathing movements start. These contractions increase cerebral blood flow by facilitating left stroke volume, cardiac output, and arterial pressure. The analysis of the compensatory mechanisms involved in maximal breath-holds can improve brain survival during conditions involving profound brain hypoperfusion and deoxygenation.

Open Access September 13, 2013

Glioma cell migration and invasion as potential target for novel treatment strategies

Ulrike Naumann, Patrick Harter, Jennifer Rubel, Elena Ilina, Anna-Eva Blank, Hugo Esteban, Michel Mittelbronn

Page range: 314-329

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Abstract

Diffuse human gliomas constitute a group of most treatment-refractory tumors even if maximum treatment strategies including neurosurgical resection followed by combined radio-/chemotherapy are applied. In contrast to most other neoplasms, diffusely infiltrating gliomas invade the brain along pre-existing structures such as axonal tracts and perivascular spaces. Even in cases of early diagnosis single or small clusters of glioma cells are already encountered far away from the main tumor bulk. Complex interactions between glioma cells and the surrounding extracellular matrix and considerable changes in the cytoskeletal apparatus are prerequisites for the cellular movement of glioma cells through the brain thereby escaping from most current treatments. This review provides an overview about classical and current concepts of glioma cell migration/invasion and promising preclinical treatment approaches.

Open Access September 13, 2013

Characterizing calcium influx via voltage- and ligand-gated calcium channels in embryonic Alligator neurons in culture

Weina Ju, Jiang Wu, Michael Pritz, Rajesh Khanna

Page range: 330-336

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Abstract

Vertebrate brains share many features in common. Early in development, both the hindbrain and diencephalon are built similarly. Only later in time do differences in morphology occur. Factors that could potentially influence such changes include certain physiological properties of neurons. As an initial step to investigate this problem, embryonic Alligator brain neurons were cultured and calcium responses were characterized. The present report is the first to document culture of Alligator brain neurons in artificial cerebrospinal fluid (ACSF) as well as in standard mammalian tissue culture medium supplemented with growth factors. Alligator brain neuron cultures were viable for at least 1 week with unipolar neurites emerging by 24 hours. Employing Fura-2 AM, robust depolarizationinduced calcium influx, was observed in these neurons. Using selective blockers of the voltage-gated calcium channels, the contributions of N-, P/Q-, R-, T-, and L-type channels in these neurons were assessed and their presence documented. Lastly, Alligator brain neurons were challenged with an excitotoxic stimulus (glutamate + glycine) where delayed calcium deregulation could be prevented by a classical NMDA receptor antagonist.

Open Access September 13, 2013

Multisensory integration and neuroplasticity in the human cerebral cortex

Evangelos Paraskevopoulos, Sibylle Herholz

Page range: 337-348

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Abstract

There is a strong interaction between multisensory processing and the neuroplasticity of the human brain. On one hand, recent research demonstrates that experience and training in various domains modifies how information from the different senses is integrated; and, on the other hand multisensory training paradigms seem to be particularly effective in driving functional and structural plasticity. Multisensory training affects early sensory processing within separate sensory domains, as well as the functional and structural connectivity between uni- and multisensory brain regions. In this review, we discuss the evidence for interactions of multisensory processes and brain plasticity and give an outlook on promising clinical applications and open questions.

Open Access September 13, 2013

Pathogenesis, modulation, and therapy of Alzheimer’s disease: A perspective on roles of liver-X receptors

Jasminka Štefulj, Ute Panzenboeck, Patrick Hof, Goran Šimić

Page range: 349-356

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Abstract

The pathogenesis of Alzheimer’s disease (AD) has been mostly linked to aberrant amyloid beta (Aβ) and tau proteins metabolism, disturbed lipid/cholesterol homeostasis, and progressive neuroinflammation. Liver X receptors (LXR) are ligand-activated transcription factors, best known as the key regulators of cholesterol metabolism and transport. In addition, LXR signaling has been shown to have significant anti-inflammatory properties. In this brief review, we focus on the outcome of studies implicating LXR in the pathogenesis, modulation, and therapy of AD.

Open Access September 13, 2013

microRNA s (9, 138, 181A, 221, and 222) and mesial temporal lobe epilepsy in developing brains

Muhammad Ashhab, Ahmed Omran, Na Gan, Huimin Kong, Jing Peng, Fei Yin

Page range: 357-362

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Abstract

Background: Recently, microRNAs (miRNAs) have attracted much attention as novel players in the pathogenesis of mesial temporal lobe epilepsy (MTLE) in mature and developing brains. This study aimed to investigate the expression dynamics of miR-9, miR-138, miR-181a, miR-221, and miR-222 in the hippocampus of an immature rat model during the three stages of MTLE development and in children with MTLE. Methodology: qPCR was used to measure expression levels during the three stages of MTLE development (2 h, 3, and 8 weeks after induction of lithium-pilocarpine status epilepticus, representing the acute, latent, and chronic stages, respectively. Expression levels were also measured in hippocampi obtained from children with MTLE and normal controls. Results: In the rat model, miR-9 was significantly upregulated during the acute and chronic stages relative to controls, but not during the latent stage. MiR-138, miR-221 and miR-222 were all downregulated during all three stages of MTLE development. MiR-181a was downregulated during the acute stage, upregulated during the chronic stage, and unaltered during the latent stage. In children, miR-9 and miR-181a were upregulated, while miR-138, miR-221, and miR-222 were downregulated. Conclusion: Modulation of these miRNAs may be a new strategy in designing antiepileptic and anticonvulsant therapies for the developing brain.

Open Access September 13, 2013

Anatomical location of transcallosal sensorimotor fibers in the human brain: Diffusion tensor tractography study

Jung Seo, Sung Jang

Page range: 363-367

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Abstract

Many diffusion tensor tractography (DTT) studies have reported on the topography of transcallosal fibers (TCF). However, little detailed anatomical information on TCF that can be easily applied for clinical purposes is known. Using probabilistic DTT, we attempted to determine the anatomical location of the TCF for motor and sensory function in the human brain. A total of 51 healthy subjects were recruited for this study. Diffusion tensor images (DTIs) were obtained at 1.5 T, and four TCF for the premotor cortex (PMC), the primary motor cortex (M1) for hand and leg, and the primary somatosensory cortex (S1) were obtained using FMRIB software. Locations of the TCF were defined as the highest probabilistic location on the midsagittal slice of the corpus callosum. We measured distances between the most anterior and posterior points of the corpus callosum. The relative mean distances of the highest probabilistic location for the precentral knob PMC (Brodmann area 6 anterior to the precentral knob), hand M1, leg M1, and precentral knob S1 (postcentral gyrus posterior to the precentral knob) TCF were 48.99%, 59.78%, 67.93%, and 73,48% from the most anterior point of the CC, respectively. According to our findings, the precentral knob PMC, hand M1, leg M1, and precentral knob S1 TCF were located at the anterior body, posterior body, posterior body, and isthmus according to Witelson’s classification, respectively.

Open Access September 13, 2013

Synthetic metacognition as a link between brain and behavior in schizophrenia

Paul Lysaker, Petr Bob, Ondrej Pec, Jay Hamm, Marina Kukula, Jen Vohs, Raffaele Popolo, Giampaolo Salvatore, Giancarlo Dimaggio

Page range: 368-377

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Abstract

Deficits in metacognitive capacity in schizophrenia can be conceptualized as existing along a spectrum from more discrete to more synthetic activities. These capacities may be of great importance in schizophrenia research given their potential to mediate and moderate the impact of illness-related factors on outcome. To explore this possibility this review summarizes research on synthetic metacognition using a paradigm in which metacognitive capacity is rated on the basis of spontaneously produced personal narratives. Evidence from a review of the literature shows that these deficits are detectable in patients with schizophrenia and are related to, but not reducible to, symptom severity and poorer neurocognitive function. Independent of symptoms and neurocognition, deficits in synthetic metacognition, which are likely linked to the brain’s ability to integrate information, are related to a range of outcomes including functional competence, learning potential, and insight. These deficits may also play a role in long term psychosocial functioning via their impact on the ability to sustain social functions.

Open Access September 13, 2013

Neural lineage development in the rhesus monkey with embryonic stem cells

Hongwei Chen, Qiang Wei, Jing Zhang, Tao Tan, Rongrong Li, Jilin Chen

Page range: 378-384

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Abstract

There are three controversial and undetermined models of neurogenesis and gliogenesis from neuroepithelial cells in the early neural tube; the first in which neurons and glia were proposed to originate from a single homogenous population, the second from two separate pools of committed glial and neuronal progenitors, or, lastly, from transit radial glial (RG). Issues concerning embryonic neural lineage development in primates are not well understood due to restrictions imposed by ethics and material sources. In this study, early neural lineage development was investigated in vitro with rhesus monkey embryonic stem cells (rESC) by means of immunofluorescence with lineage specific markers. It was revealed that neural differentiation likely progresses in a sequential lineage restriction pathway from neuroepithelial stem/progenitor cells to neurons and glia via RG and intermediate precursors: neuronal precursors and glial progenitors. In conclusion, our results suggest that the early neural lineage development of rESC in vitro supported the model in which neuroepithelial cells develop into RG capable of generating both neurons and glia. This work should facilitate understanding of the mechanism of development of the nervous system in primates.

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