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https://www.readbyqxmd.com/read/29029315/7-8-dihydroxyflavone-rescues-lead-induced-impairment-of-vesicular-release-a-novel-therapeutic-approach-for-lead-intoxicated-children
#1
Xiao-Lei Zhang, Jennifer L McGlothan, Omid Miry, Kirstie H Stansfield, Meredith K Loth, Patric K Stanton, Tomás R Guilarte
Childhood lead (Pb2+) intoxication is a public health problem of global proportion. Lead exposure during development produces multiple effects on the central nervous system including impaired synapse formation, altered synaptic plasticity, and learning deficits.In primary hippocampal neurons in culture and hippocampal slices, Pb2+ exposure inhibits vesicular release and reduces the number of fast-releasing sites, an effect associated with Pb2+ inhibition of NMDA receptor-mediated trans-synaptic Brain-Derived Neurotrophic Factor (BDNF) signaling...
October 4, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29024033/impact-of-x-irradiation-on-microglia
#2
Franziska Menzel, Nicole Kaiser, Susann Haehnel, Felicitas Rapp, Ina Patties, Nina Schöneberg, Zhana Haimon, Kerstin Immig, Ingo Bechmann
Irradiation is widely used to treat brain tumors, and also to create bone marrow (BM) chimeras. BM chimeras are widely used to dissect functions and origin of microglia and blood-derived mononuclear cells under homeostatic or pathological conditions. This is facilitated by the fact that microglia survive irradiation and are thus regarded radio-resistant. In this study, we tested whether microglia are indeed radio-resistant and looked for potential mechanisms that might explain this phenomenon. We analyzed the radio-resistance of microglia independently of their physiological brain environment compared to other mononuclear cells from spleen and brain after X-irradiation with 7 Gy or 30 Gy...
October 10, 2017: Glia
https://www.readbyqxmd.com/read/29023798/intrathecal-antibody-distribution-in-the-rat-brain-surface-diffusion-perivascular-transport-and-osmotic-enhancement-of-delivery
#3
Michelle E Pizzo, Daniel J Wolak, Niyanta N Kumar, Eric Brunette, Christina L Brunnquell, Melanie-Jane Hannocks, N Joan Abbott, M Elizabeth Meyerand, Lydia Sorokin, Danica B Stanimirovic, Robert G Thorne
The precise mechanisms governing the central distribution of macromolecules from the cerebrospinal fluid (CSF) to the brain and spinal cord remain poorly understood, despite their importance for physiological processes such as antibody trafficking for central immune surveillance as well as several ongoing intrathecal clinical trials. Here, we clarify how immunoglobulin G (IgG) and smaller single-domain antibodies (sdAb) distribute throughout the whole brain in a size-dependent manner after intrathecal infusion in rats using ex vivo fluorescence and in vivo 3D magnetic resonance imaging...
October 12, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29023523/the-role-of-glutamate-in-neuronal-ion-homeostasis-a-case-study-of-spreading-depolarization
#4
Niklas Hübel, Mahshid S Hosseini-Zare, Jokūbas Žiburkus, Ghanim Ullah
Simultaneous changes in ion concentrations, glutamate, and cell volume together with exchange of matter between cell network and vasculature are ubiquitous in numerous brain pathologies. A complete understanding of pathological conditions as well as normal brain function, therefore, hinges on elucidating the molecular and cellular pathways involved in these mostly interdependent variations. In this paper, we develop the first computational framework that combines the Hodgkin-Huxley type spiking dynamics, dynamic ion concentrations and glutamate homeostasis, neuronal and astroglial volume changes, and ion exchange with vasculature into a comprehensive model to elucidate the role of glutamate uptake in the dynamics of spreading depolarization (SD)-the electrophysiological event underlying numerous pathologies including migraine, ischemic stroke, aneurysmal subarachnoid hemorrhage, intracerebral hematoma, and trauma...
October 12, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29022339/resveratrol-ameliorates-tau-hyperphosphorylation-at-ser396-site-and-oxidative-damage-in-rat-hippocampal-slices-exposed-to-vanadate-implication-of-erk1-2-and-gsk-3%C3%AE-signaling-cascades
#5
Kyoung A Jhang, Jin-Sun Park, Hee-Sun Kim, Young Hae Chong
The objective of this study was to investigate the effect of resveratrol (a natural polyphenolic phytostilbene) on tau hyperphosphorylation and oxidative damage induced by sodium orthovanadate (Na3VO4), the prevalent species of vanadium (vanadate), in rat hippocampal slices. Our results showed that resveratrol significantly inhibited Na3VO4-induced hyperphosphorylation of tau at Ser396 (p-S396-tau) site, which is upregulated in the hippocampus of Alzheimer's disease (AD) brains and principally linked to AD-associated cognitive dysfunction...
October 12, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29021779/xenon-reduces-neuronal-hippocampal-damage-and-alters-the-pattern-of-microglial-activation-after-experimental-subarachnoid-hemorrhage-a-randomized-controlled-animal-trial
#6
Michael Veldeman, Mark Coburn, Rolf Rossaint, Hans Clusmann, Kay Nolte, Benedikt Kremer, Anke Höllig
OBJECTIVE: The neuroprotective properties of the noble gas xenon have already been demonstrated using a variety of injury models. Here, we examine for the first time xenon's possible effect in attenuating early brain injury (EBI) and its influence on posthemorrhagic microglial neuroinflammation in an in vivo rat model of subarachnoid hemorrhage (SAH). METHODS: Sprague-Dawley rats (n = 22) were randomly assigned to receive either Sham surgery (n = 9; divided into two groups) or SAH induction via endovascular perforation (n = 13, divided into two groups)...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29020614/gene-editing-in-rat-embryonic-stem-cells-to-produce-in%C3%A2-vitro-models-and-in%C3%A2-vivo-reporters
#7
Yaoyao Chen, Sonia Spitzer, Sylvia Agathou, Ragnhildur Thora Karadottir, Austin Smith
Rat embryonic stem cells (ESCs) offer the potential for sophisticated genome engineering in this valuable biomedical model species. However, germline transmission has been rare following conventional homologous recombination and clonal selection. Here, we used the CRISPR/Cas9 system to target genomic mutations and insertions. We first evaluated utility for directed mutagenesis and recovered clones with biallelic deletions in Lef1. Mutant cells exhibited reduced sensitivity to glycogen synthase kinase 3 inhibition during self-renewal...
October 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29019022/distribution-of-lacosamide-in-the-rat-brain-assessed-by-in-vitro-slice-technique
#8
Zsolt Gáll, Szende Vancea
Lacosamide is a newer anticonvulsant and is the only one that enhances the slow inactivation of voltage gated sodium channels. It is also claimed to have disease-modifying potential, but its pharmacokinetic properties have been much less discussed in the literature. In rats, lacosamide shows restricted distribution to tissues, and the brain-to-plasma partition coefficient (Kp) is only 0.553. In this study, the brain disposition of lacosamide was evaluated in rat brains, and its neuropharmacokinetic parameters (i...
October 10, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29018191/d-serine-released-by-astrocytes-in-brainstem-regulates-breathing-response-to-co2-levels
#9
S Beltrán-Castillo, M J Olivares, R A Contreras, G Zúñiga, I Llona, R von Bernhardi, J L Eugenín
Central chemoreception is essential for adjusting breathing to physiological demands, and for maintaining CO2 and pH homeostasis in the brain. CO2-induced ATP release from brainstem astrocytes stimulates breathing. NMDA receptor (NMDAR) antagonism reduces the CO2-induced hyperventilation by unknown mechanisms. Here we show that astrocytes in the mouse caudal medullary brainstem can synthesize, store, and release D-serine, an agonist for the glycine-binding site of the NMDAR, in response to elevated CO2 levels...
October 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29018134/neuronal-sirt1-silent-information-regulator-2-homologue-1-regulates-glycolysis-and-mediates-resveratrol-induced-ischemic-tolerance
#10
Kevin B Koronowski, Nathalie Khoury, Isabel Saul, Zachary B Loris, Charles H Cohan, Holly M Stradecki-Cohan, Kunjan R Dave, Juan I Young, Miguel A Perez-Pinzon
BACKGROUND AND PURPOSE: Resveratrol, at least in part via SIRT1 (silent information regulator 2 homologue 1) activation, protects against cerebral ischemia when administered 2 days before injury. However, it remains unclear if SIRT1 activation must occur, and in which brain cell types, for the induction of neuroprotection. We hypothesized that neuronal SIRT1 is essential for resveratrol-induced ischemic tolerance and sought to characterize the metabolic pathways regulated by neuronal Sirt1 at the cellular level in the brain...
October 10, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29017867/volumetric-reconstruction-from-printed-films-enabling-30-year-longitudinal-analysis-in-mr-neuroimaging
#11
Michael Ebner, Karen K Chung, Ferran Prados, M Jorge Cardoso, Declan T Chard, Tom Vercauteren, Sébastien Ourselin
Hospitals often hold historical MR image data printed on films without being able to make it accessible to modern image processing techniques. Having the possibility to recover geometrically consistent, volumetric images from scans acquired decades ago will enable more comprehensive, longitudinal studies to understand disease progressions. In this paper, we propose a consistent framework to reconstruct a volumetric representation from printed films holding thick single-slice brain MR image acquisitions dating back to the 1980's...
October 7, 2017: NeuroImage
https://www.readbyqxmd.com/read/29017728/near-infrared-fluorescent-proteins-engineered-from-bacterial-phytochromes-in-neuroimaging
#12
Kiryl D Piatkevich, Ho-Jun Suk, Suhasa B Kodandaramaiah, Fumiaki Yoshida, Ellen M DeGennaro, Mikhail Drobizhev, Thomas E Hughes, Robert Desimone, Edward S Boyden, Vladislav V Verkhusha
Several series of near-infrared (NIR) fluorescent proteins (FPs) were recently engineered from bacterial phytochromes but were not systematically compared in neurons. To fluoresce, NIR FPs utilize an enzymatic derivative of heme, the linear tetrapyrrole biliverdin, as a chromophore whose level in neurons is poorly studied. Here, we evaluated NIR FPs of the iRFP protein family, which were reported to be the brightest in non-neuronal mammalian cells, in primary neuronal culture, in brain slices of mouse and monkey, and in mouse brain in vivo...
October 7, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28989646/the-double-edged-role-of-copper-in-the-fate-of-amyloid-beta-in-the-presence-of-anti-oxidants
#13
Jing Yang, Xueli Zhang, Yiying Zhu, Emily Lenczowski, Yanli Tian, Jian Yang, Can Zhang, Markus Hardt, Chunhua Qiao, Rudolph E Tanzi, Anna Moore, Hui Ye, Chongzhao Ran
The biological fate of amyloid beta (Aβ) species is a fundamental question in Alzheimer's disease (AD) pathogenesis. The competition between clearance and aggregation of Aβs is critical for the onset of AD. Copper has been widely considered to be an inducer of harmful crosslinking of Aβs, and an important triggering factor for the onset of AD. In this report, however, we present data to show that copper can also be an inducer of Aβ degradation in the presence of a large excess of well-known intrinsic (such as dopamine) or extrinsic (such as vitamin C) anti-oxidants...
September 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28987817/the-sodium-channel-activator-lu-ae98134-normalizes-the-altered-firing-properties-of-fast-spiking-interneurons-in-dlx5-6-mice
#14
Nadia Lybøl von Schoubye, Kristen Frederiksen, Uffe Kristiansen, Anders Victor Petersen, Nils Ole Dalby, Morten Grunnet, Henrik Sindal Jensen, Thomas Jespersen, Vikaas S Sohal, Jean-François Perrier
Mental disorders such as schizophrenia are associated with impaired firing properties of fast spiking inhibitory interneurons (FSINs) causing reduced task-evoked gamma-oscillation in prefrontal cortex. The voltage-gated sodium channel NaV1.1 is highly expressed in PV-positive interneurons, but only at low levels in principal cells. Positive modulators of Nav1.1 channels are for this reason considered potential candidates for the treatment of cognitive disorders. Here we examined the effect of the novel positive modulator of voltage-gated sodium channels Lu AE98134...
October 5, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28987401/pm2-5-exposure-stimulates-cox-2-mediated-excitatory-synaptic-transmission-via-ros-nf-%C3%AE%C2%BAb-pathway
#15
Ben Li, Lin Guo, Tingting Ku, Minjun Chen, Guangke Li, Nan Sang
Long-term exposure to fine particulate matter (PM2.5) has been reported to be closely associated with the neuroinflammation and synaptic dysfunction, but the mechanisms underlying the process remain unclear. Cyclooxygenase-2 (COX-2) is a key player in neuroinflammation, and has been also implicated in the glutamatergic excitotoxicity and synaptic plasticity. Thus, we hypothesized that COX-2 was involved in PM2.5-promoted neuroinflammation and synaptic dysfunction. Our results revealed that PM2.5 elevated COX-2 expression in primary cultured hippocampal neurons and increased the amplitude of field excitatory postsynaptic potentials (fEPSPs) in hippocampal brain slices...
September 21, 2017: Chemosphere
https://www.readbyqxmd.com/read/28986933/liquid-tissue-surrogates-for-x-ray-and-ct-phantom-studies
#16
Paul F FitzGerald, Robert E Colborn, Peter M Edic, Jack W Lambert, Peter J Bonitatibus, Benjamin M Yeh
PURPOSE: To develop a simple method for producing liquid-tissue-surrogate (LTS) materials that accurately represent human soft tissues in terms of density and X-ray attenuation coefficient. METHODS AND MATERIALS: We evaluated hypothetical mixtures of water, glycerol, butanol, methanol, sodium chloride, and potassium nitrate; these mixtures were intended to emulate human adipose, blood, brain, kidney, liver, muscle, pancreas, and skin. We compared the hypothetical densities, effective atomic numbers (Zeff ), and calculated discrete-energy CT attenuation (Hounsfield Units (HU)) of the proposed materials with those of human tissue elemental composition as specified in International Commission on Radiation Units (ICRU) Report 46...
October 7, 2017: Medical Physics
https://www.readbyqxmd.com/read/28986876/electrophysiological-investigation-of-nmda-current-properties-in-brain-slices
#17
Alexandre Pons-Bennaceur, Natalia Lozovaya
Analysis of electrophysiological properties of NMDARs and NMDAR-mediated synaptic transmission in identified neurons and synapses in brain slices is a major step in understanding their function in normal and pathological neuronal brain networks. In many central synapses excitatory postsynaptic currents (EPSCs) are mediated by excitatory neurotransmitter glutamate that activates colocalized AMPAR and NMDAR generating a complex EPSC. Here, we describe the methods commonly used in brain slices to study the electrophysiological properties of NMDAR-mediated component of spontaneous or evoked EPSCs by extracellular stimulation or by stimulating synaptically connected neurons...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986868/detection-of-nmdars-antibodies-in-encephalitis
#18
Matteo Gastaldi, Patrick Waters, Angela Vincent
There is a range of diseases of the brain that are associated with rapidly developing inflammation. These conditions are called encephalitis, and can be caused by infections, or autoimmune disorders when the subject's immune system reacts against host proteins. The most common form of autoimmune encephalitis is associated with antibodies against the NR1 subunit of the N-Methyl-D-Aspartate Receptor (anti-NMDAR-encephalitis). Antibody detection is important for diagnosis, and can be performed only with techniques that preserve the full tertiary structure (conformation) of the antigen...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28982320/astroglial-connexins-as-a-therapeutic-target-for-alzheimer-s-disease
#19
Chenju Yi, Annette Koulakoff, Christian Giaume
BACKGROUND: In Alzheimer's disease (AD), modification of astrocytic properties is a well-known and documented fact, but their involvement in pathophysiology has only been examined in recent years. One distinct hallmark of AD is reactive gliosis which are represented in microglial and astrocytic phenotype changes. This reactive gliosis has been associated with changes in the expression and function of connexins. Connexins are proteins that can form gap junction channels and hemichannels, and in a disease context, have shown increased expression in astrocytes that contact amyloid plaques in vivo...
October 4, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28981586/gabapentin-prevents-progressive-increases-in-excitatory-connectivity-and-epileptogenesis-following-neocortical-trauma
#20
D K Takahashi, Sha Jin, D A Prince
Neocortical injury initiates a cascade of events, some of which result in maladaptive epileptogenic reorganization of surviving neural circuits. Research focused on molecular and organizational changes that occur following trauma may reveal processes that underlie human post-traumatic epilepsy (PTE), a common and unfortunate consequence of traumatic brain injury. The latency between injury and development of PTE provides an opportunity for prophylactic intervention, once the key underlying mechanisms are understood...
June 26, 2017: Cerebral Cortex
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