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https://www.readbyqxmd.com/read/28087836/neuropathological-consequences-of-gestational-exposure-to-concentrated-ambient-fine-and-ultrafine-particles-in-the-mouse
#1
Carolyn Klocke, Joshua L Allen, Marissa Sobolewski, Margot Mayer-Pröschel, Jason L Blum, Dana Lauterstein, Judith T Zelikoff, Deborah A Cory-Slechta
Increasing evidence indicates that the central nervous system (CNS) is a target of air pollution. We previously reported that postnatal exposure of mice to concentrated ambient ultrafine particles (UFP; ≤100nm) via the University of Rochester HUCAPS system during a critical developmental window of CNS development, equivalent to human 3(rd) trimester, produced male-predominant neuropathological and behavioral characteristics common to multiple neurodevelopmental disorders, including autism spectrum disorder (ASD), in humans...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28087191/alterations-of-brain-activity-in-fibromyalgia-patients
#2
REVIEW
Passakorn Sawaddiruk, Sahattaya Paiboonworachat, Nipon Chattipakorn, Siriporn C Chattipakorn
Fibromyalgia is a chronic pain syndrome, characterized by widespread musculoskeletal pain with diffuse tenderness at multiple tender points. Despite intense investigations, the pathophysiology of fibromyalgia remains elusive. Evidence shows that it could be due to changes in either the peripheral or central nervous system (CNS). For the CNS changes, alterations in the high brain area of fibromyalgia patients have been investigated but the definite mechanisms are still unclear. Magnetic Resonance Imaging (MRI) and Functional Magnetic Resonance (fMRI) have been used to gather evidence regarding the changes of brain morphologies and activities in fibromyalgia patients...
January 10, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28086920/absence-of-system-xc-on-immune-cells-invading-the-central-nervous-system-alleviates-experimental-autoimmune-encephalitis
#3
Ellen Merckx, Giulia Albertini, Magdalena Paterka, Cathy Jensen, Philipp Albrecht, Michael Dietrich, Joeri Van Liefferinge, Eduard Bentea, Lise Verbruggen, Thomas Demuyser, Lauren Deneyer, Jan Lewerenz, Geert van Loo, Jacques De Keyser, Hideyo Sato, Pamela Maher, Axel Methner, Ann Massie
BACKGROUND: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System xc(-) or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration...
January 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28086758/toxoplasmosis-associated-iris-involving-the-cns-a-case-report-with-longitudinal-analysis-of-t-cell-subsets
#4
Rita Rb-Silva, Claudia Nobrega, Eugénia Reiriz, Soraia Almeida, Rui Sarmento-Castro, Margarida Correia-Neves, Ana Horta
BACKGROUND: HIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality...
January 13, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28081460/blood-brain-barrier-dysfunction-induced-by-silica-nps-in%C3%A2-vitro-and-in%C3%A2-vivo-involvement-of-oxidative-stress-and-rho-kinase-jnk-signaling-pathways
#5
Xin Liu, Baiyan Sui, Jiao Sun
Silica nanoparticles (SiO2-NPs) has been extensively exploited in biomedical fields and mostly designed to enter the circulatory system, however, few studies focused on the potential adverse effects of SiO2-NPs exposure on the blood-brain barrier (BBB) that serves as a critical barrier between the central nervous system (CNS) and the peripheral circulation. This study attempts to provide an understanding of whether and how SiO2-NPs disrupts the BBB in vitro and in vivo. Through a human BBB model, we found that SiO2-NPs could induce tight junction loss and cytoskeleton arrangement, and increase inflammatory response and the release of vascular endothelial growth factor (VEGF) of brain microvessel endothelial cells (BMECs), which further activates astrocytes to amplify the generation of VEGF and increase the aquaporin-4 expression, and thus causing BBB disruption through a complex immunoregulatory loop between BMECs and astrocytes under SiO2-NPs exposure...
January 4, 2017: Biomaterials
https://www.readbyqxmd.com/read/28081177/first-behavioural-characterisation-of-a-knockout-mouse-model-for-the-transforming-growth-factor-tgf-%C3%AE-superfamily-cytokine-mic-1-gdf15
#6
Jac Kee Low, Ananthan Ambikairajah, Kani Shang, David A Brown, Vicky W W Tsai, Samuel N Breit, Tim Karl
Macrophage inhibitory cytokine-1 (MIC-1), also known as growth differentiation factor 15 (GDF15), is a stress response cytokine. MIC-1/GDF15 is secreted into the cerebrospinal fluid and increased levels of MIC-1/GDF15 are associated with a variety of diseases including cognitive decline. Furthermore, Mic-1/Gdf15 knockout mice (Mic-1 KO) weigh more, have increased adiposity, associated with increased spontaneous food intake, and exhibit reduced basal energy expenditure and physical activity. The current study was designed to comprehensively determine the role of MIC-1/GDF15 on behavioural domains of male and female knockout mice including locomotion, exploration, anxiety, cognition, social behaviours, and sensorimotor gating...
2017: PloS One
https://www.readbyqxmd.com/read/28077724/trem2-promotes-microglial-survival-by-activating-wnt-%C3%AE-catenin-pathway
#7
Honghua Zheng, Lin Jia, Chia-Chen Liu, Zhouyi Rong Li Zhong, Longyu Yang, Xiao-Fen Chen, John D Fryer, Xin Wang, Yun-Wu Zhang, Huaxi Xu, Guojun Bu
: Triggering Receptor Expressed on Myeloid cells 2 (TREM2), expressed on myeloid cells including microglia in the central nervous system (CNS), has recently been identified as a risk factor for Alzheimer's disease (AD). TREM2 transmits intracellular signals through its trans-membrane binding partner DNAX-activating protein 12 (DAP12). Homozygous mutations inactivating TREM2 or DAP12 lead to Nasu-Hakola disease (NHD); however, how AD risk-conferring variants increase AD risk is not clear...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28076777/antagonistic-functions-of-mbp-and-cnp-establish-cytosolic-channels-in-cns-myelin
#8
Nicolas Snaidero, Caroline Velte, Matti Myllykoski, Arne Raasakka, Alexander Ignatev, Hauke B Werner, Michelle S Erwig, Wiebke Möbius, Petri Kursula, Klaus-Armin Nave, Mikael Simons
The myelin sheath is a multilamellar plasma membrane extension of highly specialized glial cells laid down in regularly spaced segments along axons. Recent studies indicate that myelin is metabolically active and capable of communicating with the underlying axon. To be functionally connected to the neuron, oligodendrocytes maintain non-compacted myelin as cytoplasmic nanochannels. Here, we used high-pressure freezing for electron microscopy to study these cytoplasmic regions within myelin close to their native state...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28076313/ethnopharmacological-investigation-of-the-aerial-part-of-phragmites-karka-poaceae
#9
Ramiz Ahmed Sultan, Mohammad Shah Hafez Kabir, Mir Muhammad Nasir Uddin, Mohi Uddin, Zobaer Al Mahmud, Sheikh Zahir Raihan, Nazmul Qais
BACKGROUND: In this ethnopharmacological study, methanolic extract of the aerial plant parts of Phragmites karka (Family: Poaceae) and its petroleum ether and carbon tetrachloride fractions were investigated for bioactivities in Swiss-albino mice, namely, analgesic, central nervous system (CNS) depressant, hypoglycemic, and antidiarrheal activity. METHODS: The cold methanolic extract of the aerial plant parts of Phragmites karka (MEPK) was first prepared, and it was then further fractionated as petroleum ether (PEFMEPK) and carbon tetrachloride (CTFMEPK) fractions...
January 11, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28075486/highly-expandable-human-ips-cell-derived-neural-progenitor-cells-npc-and-neurons-for-central-nervous-system-disease-modeling-and-high-throughput-screening
#10
Chialin Cheng, Daniel M Fass, Kat Folz-Donahue, Marcy E MacDonald, Stephen J Haggarty
Reprogramming of human somatic cells into induced pluripotent stem (iPS) cells has greatly expanded the set of research tools available to investigate the molecular and cellular mechanisms underlying central nervous system (CNS) disorders. Realizing the promise of iPS cell technology for the identification of novel therapeutic targets and for high-throughput drug screening requires implementation of methods for the large-scale production of defined CNS cell types. Here we describe a protocol for generating stable, highly expandable, iPS cell-derived CNS neural progenitor cells (NPC) using multi-dimensional fluorescence activated cell sorting (FACS) to purify NPC defined by cell surface markers...
January 11, 2017: Current Protocols in Human Genetics
https://www.readbyqxmd.com/read/28073831/deletion-of-protein-kinase-c-lambda-in-pomc-neurons-predisposes-to-diet-induced-obesity
#11
Mauricio D Dorfman, Jordan E Krull, Jarrad M Scarlett, Stephan J Guyenet, Mini P Sajan, Vincent Damian, Hong T Nguyen, Michael Leitges, Gregory J Morton, Robert V Farese, Michael W Schwartz, Joshua P Thaler
Effectors of the phosphoinositide 3-kinase (PI3K) signal transduction pathway contribute to the hypothalamic regulation of energy and glucose homeostasis in divergent ways. Here we show that CNS action of the PI3K signaling intermediate atypical protein kinase C (aPKC) constrains food intake, weight gain, and glucose intolerance in both rats and mice. Pharmacologic inhibition of CNS aPKC activity acutely increases food intake and worsens glucose tolerance in chow-fed rodents and causes excess weight gain during high fat diet (HFD) feeding...
January 10, 2017: Diabetes
https://www.readbyqxmd.com/read/28070871/treating-hiv-infection-in-the-central-nervous-system
#12
REVIEW
A Calcagno, G Di Perri, S Bonora
Combination antiretroviral treatment is associated with clear benefits in HIV-positive subjects, and is also effective in the central nervous system (CNS), meaning HIV-associated dementia is now an uncommon event. Nevertheless, a significant number of patients show symptoms of neurocognitive impairment which may negatively affect their quality of life. Although several risk factors for HIV-associated neurocognitive disorders have been identified, there is no clear recommendation for their prevention and management...
January 9, 2017: Drugs
https://www.readbyqxmd.com/read/28070834/resveratrol-modulates-gsh-system-in-c6-astroglial-cells-through-heme-oxygenase-1-pathway
#13
Bernardo Assein Arús, Débora Guerini Souza, Bruna Bellaver, Diogo Onofre Souza, Carlos-Alberto Gonçalves, André Quincozes-Santos, Larissa Daniele Bobermin
Resveratrol is a dietary polyphenol that displays neuroprotective properties in several in vivo and in vitro experimental models, by modulating oxidative and inflammatory responses. Glutathione (GSH) is a key antioxidant in the central nervous system (CNS) that modulates several cellular processes, and its depletion is associated with oxidative stress and inflammation. Therefore, this study sought to investigate the protective effects of resveratrol against GSH depletion pharmacologically induced by buthionine sulfoximine (BSO) in C6 astroglial cells, as well as its underlying cellular mechanisms...
January 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28070747/enhanced-bulbar-function-in-amyotrophic-lateral-sclerosis-the-nuedexta-treatment-trial
#14
Richard Smith, Erik Pioro, Kathleen Myers, Michael Sirdofsky, Kimberly Goslin, Gregg Meekins, Hong Yu, James Wymer, Merit Cudkowicz, Eric A Macklin, David Schoenfeld, Gary Pattee
The goal of this randomized, blinded, crossover clinical trial was to determine whether Nuedexta (dextromethorphan and quinidine) enhanced speech, swallowing, and salivation in patients with ALS. Sixty patients with amyotrophic lateral sclerosis (ALS) received either Nuedexta or placebo for 28 to 30 days, followed by a 10 to 15-day washout period. Subsequently, patients were switched to the opposite treatment arm for the remaining days of the trial. The primary endpoint was a reduction in the self-report Center for Neurologic Study Bulbar Function Scale (CNS-BFS) score...
January 9, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28070126/lipocalin-2-protects-the-brain-during-inflammatory-conditions
#15
S S Kang, Y Ren, C-C Liu, A Kurti, K E Baker, G Bu, Y Asmann, J D Fryer
Sepsis is a prevalent health issue that can lead to central nervous system (CNS) inflammation with long-term behavioral and cognitive alterations. Using unbiased proteomic profiling of over 100 different cytokines, we found that Lipocalin-2 (LCN2) was the most substantially elevated protein in the CNS after peripheral administration of lipopolysaccharide (LPS). To determine whether the high level of LCN2 in the CNS is protective or deleterious, we challenged Lcn2(-/-) mice with peripheral LPS and determined effects on behavior and neuroinflammation...
January 10, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28069965/dual-role-of-alcam-in-neuroinflammation-and-blood-brain-barrier-homeostasis
#16
Marc-André Lécuyer, Olivia Saint-Laurent, Lyne Bourbonnière, Sandra Larouche, Catherine Larochelle, Laure Michel, Marc Charabati, Michael Abadier, Stephanie Zandee, Neda Haghayegh Jahromi, Elizabeth Gowing, Camille Pittet, Ruth Lyck, Britta Engelhardt, Alexandre Prat
Activated leukocyte cell adhesion molecule (ALCAM) is a cell adhesion molecule found on blood-brain barrier endothelial cells (BBB-ECs) that was previously shown to be involved in leukocyte transmigration across the endothelium. In the present study, we found that ALCAM knockout (KO) mice developed a more severe myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis (EAE). The exacerbated disease was associated with a significant increase in the number of CNS-infiltrating proinflammatory leukocytes compared with WT controls...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28069928/functional-organization-of-cutaneous-and-muscle-afferent-synapses-onto-immature-spinal-lamina-i-projection-neurons
#17
Jie Li, Mark L Baccei
: It is well-established that sensory afferents innervating muscle are more effective at inducing hyperexcitability within spinal cord circuits compared to skin afferents, which likely contributes to the higher prevalence of chronic musculoskeletal pain compared to pain of cutaneous origin. However, the mechanisms underlying these differences in central nociceptive signaling remain incompletely understood, as nothing is known about how superficial dorsal horn (SDH) neurons process sensory input from muscle vs...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28069825/intravenous-anesthetic-propofol-binds-to-5-lipoxygenase-and-attenuates-leukotriene-b4-production
#18
Toshiaki Okuno, Sophia Koutsogiannaki, Mai Ohba, Matthew Chamberlain, Weiming Bu, Fu-Yan Lin, Roderic G Eckenhoff, Takehiko Yokomizo, Koichi Yuki
Propofol is an intravenous anesthetic that produces its anesthetic effect, largely via the GABAA receptor in the CNS, and also reduces the N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced neutrophil respiratory burst. Because fMLP-stimulated neutrophils produce leukotriene (LT)B4, we examined the effect of propofol on LTB4 production in vivo and in vitro Cecal ligation and puncture surgery was performed in mice, with or without exposure to propofol. Propofol attenuated the production of 5-lipoxygenase (5-LOX)-related arachidonic acid (AA) derivatives in the peritoneal fluid...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28069541/a-bispecific-tribody-pet-radioligand-for-visualization-of-amyloid-beta-protofibrils-a-new-concept-for-neuroimaging
#19
Stina Syvänen, Xiaotian T Fang, Greta Hultqvist, Silvio R Meier, Lars Lannfelt, Dag Sehlin
Antibodies are highly specific for their target molecules, but their poor brain penetrance has restricted their use as PET ligands for imaging of targets within the CNS. The aim of this study was to develop an antibody-based radioligand, using the Tribody(TM) format, for PET imaging of soluble amyloid-beta (Aβ) protofibrils, which are suggested to cause neurodegeneration in Alzheimer's disease. Antibodies, even when expressed in smaller engineered formats, are large molecules that do not enter the brain in sufficient amounts for imaging purposes...
January 6, 2017: NeuroImage
https://www.readbyqxmd.com/read/28067623/seizure-control-through-genetic-and-pharmacological-manipulation-of-pumilio-a-key-component-of-neuronal-homeostasis
#20
Wei-Hsiang Lin, Carlo N G Giachello, Richard A Baines
Epilepsy is a significant disorder for which approximately one-third of patients do not respond to drug treatments. Next-generation drugs, which interact with novel targets, are required to provide a better clinical outcome for these individuals. To identify potential novel targets for antiepileptic drug (AED) design, we used RNA sequencing to identify changes in gene transcription in two seizure models of the fruitfly Drosophila melanogaster The first model compared gene transcription between wildtype (WT) and the bangsenseless(1) (para(bss)) mutant; a gain-of-function in the sole fly voltage-gated sodium channel (paralytic)...
December 14, 2016: Disease Models & Mechanisms
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