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https://www.readbyqxmd.com/read/28526411/jnj10181457-a-histamine-h3-receptor-inverse-agonist-regulates-in-vivo-microglial-functions-and-improves-depression-like-behaviours-in-mice
#1
Tomomitsu Iida, Takeo Yoshikawa, Anikó Kárpáti, Takuro Matsuzawa, Haruna Kitano, Asuka Mogi, Ryuichi Harada, Fumito Naganuma, Tadaho Nakamura, Kazuhiko Yanai
Brain histamine acts as a neurotransmitter and regulates various physiological functions, such as learning and memory, sleep-wake cycles, and appetite regulation. We have recently shown that histamine H3 receptor (H3R) is expressed in primary mouse microglia and has a strong influence on critical functions in microglia, including chemotaxis, phagocytosis, and cytokine secretion in vitro. However, the importance of H3R in microglial activity in vivo remains unknown. Here, we examined the effects of JNJ10181457 (JNJ), a selective and potent H3R inverse agonist, on microglial functions ex vivo and in vivo...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28525544/bistability-causality-and-complexity-in-cortical-networks-an-in-vitro-perturbational-study
#2
Mattia D'Andola, Beatriz Rebollo, Adenauer G Casali, Julia F Weinert, Andrea Pigorini, Rosa Villa, Marcello Massimini, Maria V Sanchez-Vives
Measuring the spatiotemporal complexity of cortical responses to direct perturbations provides a reliable index of the brain's capacity for consciousness in humans under both physiological and pathological conditions. Upon loss of consciousness, the complex pattern of causal interactions observed during wakefulness collapses into a stereotypical slow wave, suggesting that cortical bistability may play a role. Bistability is mainly expressed in the form of slow oscillations, a default pattern of activity that emerges from cortical networks in conditions of functional or anatomical disconnection...
May 19, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28524543/snapshot-whole-brain-t1-relaxometry-using-steady-state-prepared-spiral-multislice-variable-flip-angle-imaging
#3
Rahel Heule, Josef Pfeuffer, Oliver Bieri
PURPOSE: Variable flip angle (VFA) imaging is widely used for whole-brain T1 quantification. Because of the requirement to acquire at least two sets of MR images at different flip angles, VFA relaxometry is relatively slow. Here, whole-brain VFA T1 mapping at 1.5 T is accelerated by using efficient spiral non-Cartesian imaging METHODS: To quantify T1 in the human brain, radiofrequency spoiled gradient-echo imaging is performed at two optimized flip angles using an interleaved 2D multislice sequence with high spoiling efficiency...
May 19, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28524099/metabolomics-of-therapy-response-in-preclinical-glioblastoma-a-multi-slice-mrsi-based-volumetric-analysis-for-noninvasive-assessment-of-temozolomide-treatment
#4
Nuria Arias-Ramos, Laura Ferrer-Font, Silvia Lope-Piedrafita, Victor Mocioiu, Margarida Julià-Sapé, Martí Pumarola, Carles Arús, Ana Paula Candiota
Glioblastoma (GBM) is the most common aggressive primary brain tumor in adults, with a short survival time even after aggressive therapy. Non-invasive surrogate biomarkers of therapy response may be relevant for improving patient survival. Previous work produced such biomarkers in preclinical GBM using semi-supervised source extraction and single-slice Magnetic Resonance Spectroscopic Imaging (MRSI). Nevertheless, GBMs are heterogeneous and single-slice studies could prevent obtaining relevant information. The purpose of this work was to evaluate whether a multi-slice MRSI approach, acquiring consecutive grids across the tumor, is feasible for preclinical models and may produce additional insight into therapy response...
May 18, 2017: Metabolites
https://www.readbyqxmd.com/read/28523496/imaging-ms-of-rodent-ocular-tissues-and-the-optic-nerve
#5
David M G Anderson, Wendi Lambert, David J Calkins, Zsolt Ablonczy, Rosalie K Crouch, Richard M Caprioli, Kevin L Schey
The visual system is comprised of many specialized cell types that are essential for relaying sensory information about an animal's surroundings to the brain. The cells present in ocular tissue are notoriously delicate, making it particularly challenging to section thin slices of unfixed tissue. Maintaining the morphology of the native tissue is crucial for accurate observations by either conventional staining techniques or in this instance matrix-assisted laser desorption ionization (MALDI IMS) or imaging using mass spectrometry...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28522470/three-dimensional-ca-2-imaging-advances-understanding-of-astrocyte-biology
#6
Erika Bindocci, Iaroslav Savtchouk, Nicolas Liaudet, Denise Becker, Giovanni Carriero, Andrea Volterra
Astrocyte communication is typically studied by two-dimensional calcium ion (Ca(2+)) imaging, but this method has not yielded conclusive data on the role of astrocytes in synaptic and vascular function. We developed a three-dimensional two-photon imaging approach and studied Ca(2+) dynamics in entire astrocyte volumes, including during axon-astrocyte interactions. In both awake mice and brain slices, we found that Ca(2+) activity in an individual astrocyte is scattered throughout the cell, largely compartmented between regions, preponderantly local within regions, and heterogeneously distributed regionally and locally...
May 19, 2017: Science
https://www.readbyqxmd.com/read/28514188/the-invisibility-of-mild-traumatic-brain-injury-impaired-cognitive-performance-as-a-silent-symptom
#7
Leore R Heim, Miaad Badar, Shahaf Edut, Lital Rachmany, Renana Baratz, Ran Lin, Aviya Elpaz, Doaa Qubty, Lior Bikovski, Vardit Rubovitch, Shaul Schreiber, Chaim G Pick
The present study was designed to tackle two notorious features of mild Traumatic Brain Injury (mTBI) - heterogeneity and invisibility - by characterizing the full scope of mTBI symptoms. Mice were exposed to brain injuries of different intensities utilizing a weight-drop model (10, 30, 50, and 70g), and subsequently subjected to a comprehensive battery of behavioral tests at different time points, and immunohistochemical examination of cortical slices. While the physiological, neurological, emotional, and motor function of mTBI mice, i...
May 17, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28507508/improving-focal-photostimulation-of-cortical-neurons-with-pre-derived-wavefront-correction
#8
Julian M C Choy, Sharmila S Sané, Woei M Lee, Christian Stricker, Hans A Bachor, Vincent R Daria
Recent progress in neuroscience to image and investigate brain function has been made possible by impressive developments in optogenetic and opto-molecular tools. Such research requires advances in optical techniques for the delivery of light through brain tissue with high spatial resolution. The tissue causes distortions to the wavefront of the incoming light which broadens the focus and consequently reduces the intensity and degrades the resolution. Such effects are detrimental in techniques requiring focal stimulation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28507129/nonpeptide-orexin-type-2-receptor-agonist-ameliorates-narcolepsy-cataplexy-symptoms-in-mouse-models
#9
Yoko Irukayama-Tomobe, Yasuhiro Ogawa, Hiromu Tominaga, Yukiko Ishikawa, Naoto Hosokawa, Shinobu Ambai, Yuki Kawabe, Shuntaro Uchida, Ryo Nakajima, Tsuyoshi Saitoh, Takeshi Kanda, Kaspar Vogt, Takeshi Sakurai, Hiroshi Nagase, Masashi Yanagisawa
Narcolepsy-cataplexy is a debilitating disorder of sleep/wakefulness caused by a loss of orexin-producing neurons in the lateroposterior hypothalamus. Genetic or pharmacologic orexin replacement ameliorates symptoms in mouse models of narcolepsy-cataplexy. We have recently discovered a potent, nonpeptide OX2R-selective agonist, YNT-185. This study validates the pharmacological activity of this compound in OX2R-transfected cells and in OX2R-expressing neurons in brain slice preparations. Intraperitoneal, and intracerebroventricular, administration of YNT-185 suppressed cataplexy-like episodes in orexin knockout and orexin neuron-ablated mice, but not in orexin receptor-deficient mice...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28506823/hyperammonemia-compromises-glutamate-metabolism-and-reduces-bdnf-in-the-rat-hippocampus
#10
Fabiana Galland, Elisa Negri, Carollina Da Ré, Fernanda Fróes, Liliane Strapazzon, Maria Cristina Guerra, Lucas Silva Tortorelli, Carlos-Alberto Gonçalves, Marina Concli Leite
Ammonia is putatively the major toxin associated with hepatic encephalopathy (HE), a neuropsychiatric manifestation that results in cognitive impairment, poor concentration and psychomotor alterations. The hippocampus, a brain region involved in cognitive impairment and depressive behavior, has been studied less than neocortical regions. Herein, we investigated hippocampal astrocyte parameters in a hyperammonemic model without hepatic lesion and in acute hippocampal slices exposed to ammonia. We also measured hippocampal BDNF, a neurotrophin commonly related to synaptic plasticity and cognitive deficit, and peripheral S100B protein, used as a marker for brain damage...
May 12, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28504693/cyclin-dependent-kinase-7-is-a-therapeutic-target-in-high-grade-glioma
#11
S A Greenall, Y C Lim, C B Mitchell, K S Ensbey, B W Stringer, A L Wilding, G M O'Neill, K L McDonald, D J Gough, B W Day, T G Johns
High-grade glioma (HGG) is an incurable brain cancer. The transcriptomes of cells within HGG tumors are highly heterogeneous. This renders the tumors unresponsive or able to adapt to therapeutics targeted at single pathways, thereby causing treatment failure. To overcome this, we focused on cyclin-dependent kinase 7 (CDK7), a ubiquitously expressed molecule involved in two major drivers of HGG pathogenesis: cell cycle progression and RNA polymerase-II-based transcription. We tested the activity of THZ1, an irreversible CDK7 inhibitor, on patient-derived primary HGG cell lines and ex vivo HGG patient tissue slices, using proliferation assays, microarray analysis, high-resolution respirometry, cell cycle analysis and in vivo tumor orthografts...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28499835/reactive-oxygen-species-generation-increases-in-cerebral-cortex-slices-after-the-transiently-enhanced-metabolic-activity
#12
Toru Sasaki, Takuji Awaji, Kazuyoshi Shimada, Haruyo Sasaki
Under certain conditions such as hypoxia-reoxygenation, the generation of reactive oxygen species (ROS) increases following hypoxia caused by a decreased oxygen supply. As another hypoxic condition, an excess neural activity status including epileptic seizure induces a decrease in tissue oxygen partial pressure (pO2) caused by enhanced oxygen utilization; however, whether ROS generation increases following the hypoxic status induced by transiently enhanced energy metabolism in brain tissue currently remains unknown...
May 9, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28494861/excitatory-microcircuits-within-superficial-layers-of-the-medial-entorhinal-cortex
#13
Jochen Winterer, Nikolaus Maier, Christian Wozny, Prateep Beed, Jörg Breustedt, Roberta Evangelista, Yangfan Peng, Tiziano D'Albis, Richard Kempter, Dietmar Schmitz
The distinctive firing pattern of grid cells in the medial entorhinal cortex (MEC) supports its role in the representation of space. It is widely believed that the hexagonal firing field of grid cells emerges from neural dynamics that depend on the local microcircuitry. However, local networks within the MEC are still not sufficiently characterized. Here, applying up to eight simultaneous whole-cell recordings in acute brain slices, we demonstrate the existence of unitary excitatory connections between principal neurons in the superficial layers of the MEC...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28491938/synthesis-of-practical-red-fluorescent-probe-for-cytoplasmic-calcium-ions-with-greatly-improved-cell-membrane-permeability
#14
Kazuhisa Hirabayashi, Kenjiro Hanaoka, Takahiro Egawa, Chiaki Kobayashi, Shodai Takahashi, Toru Komatsu, Tasuku Ueno, Takuya Terai, Yuji Ikegaya, Tetsuo Nagano, Yasuteru Urano
In this data article, we described the detailed synthetic procedure and the experimental data for the synthesis of a red-fluorescent probe for calcium ions (Ca(2+)) with improved water solubility. This Ca(2+) red-fluorescent probe CaTM-3 AM could be applied to fluorescence imaging of physiological Ca(2+) concentration changes in not only live cells, but also brain slices, with high cell-membrane permeability leading to bright fluorescence in biosamples. The data provided herein are in association with the research article "The Development of Practical Red Fluorescent Probe for Cytoplasmic Calcium Ions with Greatly Improved Cell-membrane Permeability" in Cell Calcium (Hirabayashi et al...
June 2017: Data in Brief
https://www.readbyqxmd.com/read/28491492/associations-between-hippocampal-morphometry-and-neuropathologic-markers-of-alzheimer-s-disease-using-7%C3%A2-t-mri
#15
Anna E Blanken, Sona Hurtz, Chris Zarow, Kristina Biado, Hedieh Honarpisheh, Johanne Somme, Jenny Brook, Spencer Tung, Emily Kraft, Darrick Lo, Denise W Ng, Harry V Vinters, Liana G Apostolova
Hippocampal atrophy, amyloid plaques, and neurofibrillary tangles are established pathologic markers of Alzheimer's disease. We analyzed the temporal lobes of 9 Alzheimer's dementia (AD) and 7 cognitively normal (NC) subjects. Brains were scanned post-mortem at 7 Tesla. We extracted hippocampal volumes and radial distances using automated segmentation techniques. Hippocampal slices were stained for amyloid beta (Aβ), tau, and cresyl violet to evaluate neuronal counts. The hippocampal subfields, CA1, CA2, CA3, CA4, and subiculum were manually traced so that the neuronal counts, Aβ, and tau burden could be obtained for each region...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28490644/background-noise-exerts-diverse-effects-on-the-cortical-encoding-of-foreground-sounds
#16
Brian James Malone, Marc A Heiser, Ralph Eugene Beitel, Christoph E Schreiner
In natural listening conditions, many sounds must be detected and identified in the context of competing sound sources which function as background noise. Traditionally, noise is thought to degrade the cortical representation of sounds by suppressing responses and increasing response variability. However, recent studies of neural network models and brain slices have shown that background synaptic noise can improve the detection of signals. Because acoustic noise affects the synaptic background activity of cortical networks, it may improve the cortical responses to signals...
May 10, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28488209/mir-135a-regulates-synaptic-transmission-and-anxiety-like-behavior-in-amygdala
#17
Cecilia Mannironi, Antonio Biundo, Samyutha Rajendran, Francesca De Vito, Luana Saba, Silvia Caioli, Cristina Zona, Teresa Ciotti, Silvana Caristi, Emerald Perlas, Giorgia Del Vecchio, Irene Bozzoni, Arianna Rinaldi, Andrea Mele, Carlo Presutti
MicroRNAs are a class of non-coding RNAs with a growing relevance in the regulation of gene expression related to brain function and plasticity. They have the potential to orchestrate complex phenomena, such as the neuronal response to homeostatic challenges. We previously demonstrated the involvement of miR-135a in the regulation of early stress response. In the present study, we examine the role of miR-135a in stress-related behavior. We show that the knockdown (KD) of miR-135a in the mouse amygdala induces an increase in anxiety-like behavior...
May 9, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28488007/effects-of-rat-anti-mouse-interleukin-6-receptor-antibody-on-the-recovery-of-cognitive-function-in-stroke-mice
#18
Jun Wei, Chongling Sun, Chang Liu, Qimei Zhang
This study aimed to investigate the effects of rat anti-mouse interleukin (IL)-6 receptor antibody (MR16-1) on the recovery of cognitive function in stroke mice. Adult male C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO). Mice were randomly assigned into three groups: sham group, model group, and MR16-1 group. After the treatment of MR16-1, spatial learning and memory performance of mice were evaluated by the Morris water maze (MWM) and Y-maze tests. Then, brain slices were obtained and infarct volume and neuronal apoptosis were assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining and Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, respectively...
May 9, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28487399/the-zinc-paradigm-for-metalloneurochemistry
#19
REVIEW
Chelsea A Barr, Shawn C Burdette
Neurotransmission and sensory perception are shaped through metal ion-protein interactions in various brain regions. The term "metalloneurochemistry" defines the unique field of bioinorganic chemistry focusing on these processes, and zinc has been the leading target of metalloneurochemists in the almost 15 years since the definition was introduced. Zinc in the hippocampus interacts with receptors that dictate ion flow and neurotransmitter release. Understanding the intricacies of these interactions is crucial to uncovering the role that zinc plays in learning and memory...
May 9, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28486923/kynurenic-acid-and-neuroprotective-activity-of-the-ketogenic-diet-in-the-eye
#20
Tomasz Żarnowski, Maria Tulidowicz-Bielak, Iwona Żarnowska, Krystyna Mitosek-Szewczyk, Artur Wnorowski, Krzysztof Jóźwiak, Maciej Gasior, Waldemar A Turski
There is growing evidence of the involvement of the kynurenine metabolic pathway and the enhancement of kynurenic acid (KYNA) production in the neuroprotective effects of the ketogenic diet (KD). KD and ketone bodies (KBs) that are elevated during exposure to the KD each have a neuroprotective effect on retinal ganglion cells in a rat model of N-methyl-D-aspartate (NMDA)-induced neuronal damage. Chronic exposure to KD also increases KYNA concentrations in discrete rat brain structures. A non-selective glutamate receptor agonist, glutamate, also decreases the production of KYNA in bovine retinal slices; this effect is attenuated by acetoacetate and β-hydroxybutyrate, two of three KBs overproduced during KD...
May 9, 2017: Current Medicinal Chemistry
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