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https://www.readbyqxmd.com/read/28086931/the-release-and-trans-synaptic-transmission-of-tau-via-exosomes
#1
Yipeng Wang, Varun Balaji, Senthilvelrajan Kaniyappan, Lars Krüger, Stephan Irsen, Katharina Tepper, RamReddy Chandupatla, Walter Maetzler, Anja Schneider, Eckhard Mandelkow, Eva-Maria Mandelkow
BACKGROUND: Tau pathology in AD spreads in a hierarchical pattern, whereby it first appears in the entorhinal cortex, then spreads to the hippocampus and later to the surrounding areas. Based on this sequential appearance, AD can be classified into six stages ("Braak stages"). The mechanisms and agents underlying the progression of Tau pathology are a matter of debate. Emerging evidence indicates that the propagation of Tau pathology may be due to the transmission of Tau protein, but the underlying pathways and Tau species are not well understood...
January 13, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28072466/chronic-pain-and-impaired-glial-glutamate-transporter-function-in-lupus-prone-mice-are-ameliorated-by-blocking-csf-1-receptors
#2
Xisheng Yan, Dylan W Maixner, Fen Li, Han-Rong Weng
Systemic lupus erythematosus (SLE) is a multi-organ disease of unknown etiology in which the normal immune responses are directed against the body's own healthy tissues. Patients with SLE often suffer from chronic pain. Currently, no animal studies have been reported about the mechanisms underlying pain in SLE. In this study, the development of chronic pain in MRL lupus-prone (MRL/lpr) mice, a well-established lupus mouse model, was characterized for the first time. We found that female MRL/lpr mice developed thermal hyperalgesia at the age of 13 weeks, and mechanical allodynia at the age of 16 weeks...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28070266/serum-and-cerebrospinal-fluid-immune-mediators-in-children-with-autistic-disorder-a-longitudinal-study
#3
Carlos A Pardo, Cristan A Farmer, Audrey Thurm, Fatma M Shebl, Jorjetta Ilieva, Simran Kalra, Susan Swedo
BACKGROUND: The causes of autism likely involve genetic and environmental factors that influence neurobiological changes and the neurological and behavioral features of the disorder. Immune factors and inflammation are hypothesized pathogenic influences, but have not been examined longitudinally. METHODS: In a cohort of 104 participants with autism, we performed an assessment of immune mediators such as cytokines, chemokines, or growth factors in serum and cerebrospinal fluid (n = 67) to determine potential influences of such mediators in autism...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28039552/cerebrospinal-fluid-microglia-and-neurodegenerative-markers-in-twins-concordant-and-discordant-for-psychotic-disorders
#4
Viktoria Johansson, Joel Jakobsson, Rebecca G Fortgang, Henrik Zetterberg, Kaj Blennow, Tyrone D Cannon, Christina M Hultman, Lennart Wetterberg, Mikael Landén
Schizophrenia and bipolar disorder are debilitating psychiatric disorders with partially shared symptomatology including psychotic symptoms and cognitive impairment. Aberrant levels of microglia and neurodegenerative cerebrospinal fluid (CSF) markers have previously been found in schizophrenia and bipolar disorder. We aimed to analyze familial and environmental influences on these CSF markers and their relation to psychiatric symptoms and cognitive ability. CSF was collected from 17 complete twin pairs, nine monozygotic and eight dizygotic, and from one twin sibling...
December 30, 2016: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/28007893/young-microglia-restore-amyloid-plaque-clearance-of-aged-microglia
#5
Anna Daria, Alessio Colombo, Gemma Llovera, Heike Hampel, Michael Willem, Arthur Liesz, Christian Haass, Sabina Tahirovic
Alzheimer's disease (AD) is characterized by deposition of amyloid plaques, neurofibrillary tangles, and neuroinflammation. In order to study microglial contribution to amyloid plaque phagocytosis, we developed a novel ex vivo model by co-culturing organotypic brain slices from up to 20-month-old, amyloid-bearing AD mouse model (APPPS1) and young, neonatal wild-type (WT) mice. Surprisingly, co-culturing resulted in proliferation, recruitment, and clustering of old microglial cells around amyloid plaques and clearance of the plaque halo...
December 21, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27974666/early-changes-in-csf-strem2-in-dominantly-inherited-alzheimer-s-disease-occur-after-amyloid-deposition-and-neuronal-injury
#6
Marc Suárez-Calvet, Miguel Ángel Araque Caballero, Gernot Kleinberger, Randall J Bateman, Anne M Fagan, John C Morris, Johannes Levin, Adrian Danek, Michael Ewers, Christian Haass
Emerging evidence supports a role for innate immunity and microglia in Alzheimer's disease (AD) pathophysiology. However, no marker related to microglia has been included in the temporal evolution models of AD. TREM2 is a transmembrane protein involved in innate immunity and is selectively expressed by microglia and genetically linked to AD and other neurodegenerative disorders. Its ectodomain is released by proteolysis as a soluble variant (sTREM2) and can be detected in the cerebrospinal fluid (CSF). In patients with autosomal dominant AD, we tested how many years before the expected symptom onset did CSF sTREM2 increase in mutation carriers (MCs) compared to noncarriers (NCs)...
December 14, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27932954/neuronal-release-of-cytokine-il-3-triggered-by-mechanosensitive-autostimulation-of-the-p2x7-receptor-is-neuroprotective
#7
Jason C Lim, Wennan Lu, Jonathan M Beckel, Claire H Mitchell
Mechanical strain due to increased pressure or swelling activates inflammatory responses in many neural systems. As cytokines and chemokine messengers lead to both pro-inflammatory and neuroprotective actions, understanding the signaling patterns triggered by mechanical stress may help improve overall outcomes. While cytokine signaling in neural systems is often associated with glial cells like astrocytes and microglia, the contribution of neurons themselves to the cytokine response is underappreciated and has bearing on any balanced response...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27832087/subarachnoid-hemorrhage-promotes-proliferation-differentiation-and-migration-of-neural-stem-cells-via-bdnf-upregulation
#8
Wen-Di Lee, Kuo-Chuan Wang, Yi-Fen Tsai, Pin-Chun Chou, Li-Kai Tsai, Chung-Liang Chien
Patients who suffer from subarachnoid hemorrhage (SAH) usually have long-term neurological impairments. Endogenous neurogenesis might play a potential role in functional recovery after SAH; however, the underlying neurogenesis mechanism is still unclear. We assessed the extent of neurogenesis in the subventricular zone (SVZ) to better understand the neurogenesis mechanism after SAH. We performed a rat model of SAH to examine the extent of neurogenesis in the SVZ and assessed functional effects of the neurotrophic factors in the cerebrospinal fluid (CSF) on neural stem cells (NSCs) after SAH...
2016: PloS One
https://www.readbyqxmd.com/read/27813239/combined-tissue-and-fluid-proteomics-with-tandem-mass-tags-to-identify-low-abundance-protein-biomarkers-of-disease-in-peripheral-body-fluid-an-alzheimer-s-disease-case-study
#9
Claire L Russell, Amanda Heslegrave, Vikram Mitra, Henrik Zetterberg, Jennifer M Pocock, Malcolm A Ward, Ian Pike
RATIONALE: Ideal biomarkers are present in readily accessible samples including plasma and cerebrospinal fluid (CSF), and are directly derived from diseased tissue, therefore likely to be of relatively low abundance. Traditional unbiased proteomic approaches for biomarker discovery have struggled to detect low-abundance markers due to the high dynamic range of proteins, the predominance of hyper-abundant proteins, and the use of data-dependent acquisition mass spectrometry (MS). To overcome these limitations and improve biomarker discovery in peripheral fluids, we have developed TMTcalibrator™; a novel MS workflow combining isobarically labelled diseased tissue digests in parallel with an appropriate set of labelled body fluids to increase the chance of identifying low-abundance, tissue-derived biomarkers...
January 30, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/27779463/a-zebrafish-live-imaging-model-reveals-differential-responses-of-microglia-toward-glioblastoma-cells-in-vivo
#10
Lloyd Hamilton, Katy R Astell, Gergana Velikova, Dirk Sieger
Glioblastoma multiforme is the most common and deadliest form of brain cancer. Glioblastomas are infiltrated by a high number of microglia, which promote tumor growth and surrounding tissue invasion. However, it is unclear how microglia and glioma cells physically interact and if there are differences, depending on glioma cell type. Hence, we have developed a novel live imaging assay to study microglia-glioma interactions in vivo in the zebrafish brain. We transplanted well-established human glioblastoma cell lines, U87 and U251, into transgenic zebrafish lines with labelled macrophages/microglia...
December 2016: Zebrafish
https://www.readbyqxmd.com/read/27722366/differential-regulation-of-nsc-phenotype-and-genotype-by-chronically-activated-microglia-within-cocultures
#11
Kurt Farrell, Ali Borazjani, Margot Damaser, Chandrasekhar R Kothapalli
Under disease or injury conditions in the central nervous system (CNS), activated microglia release cytokines and chemokines to modulate the microenvironment and influence tissue remodeling. To exploit the full potential of neural stem cell (NSC) transplantation approaches, a permissive microenvironment needs to be created for their survival, homing and differentiation. To investigate the role of chronically activated microglia in the fate of NSCs, spontaneously immortalized murine microglial cells (SIM-A9) were cocultured with embryonic murine cortical NSCs on 2D substrates or within 3D gels...
October 10, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/27687148/cathepsin-s-contributes-to-microglia-mediated-olfactory-dysfunction-through-the-regulation-of-cx3cl1-cx3cr1-axis-in-a-niemann-pick-disease-type-c1-model
#12
Yoojin Seo, Hyung-Sik Kim, Insung Kang, Soon Won Choi, Tae-Hoon Shin, Ji-Hee Shin, Byung-Chul Lee, Jin Young Lee, Jae-Jun Kim, Myung Geun Kook, Kyung-Sun Kang
Microglia can aggravate olfactory dysfunction by mediating neuronal death in the olfactory bulb (OB) of a murine model of Niemann-Pick disease type C1 (NPC1), a fatal neurodegenerative disorder accompanied by lipid trafficking defects. In this study, we focused on the crosstalk between neurons and microglia to elucidate the mechanisms underlying extensive microgliosis in the NPC1-affected brain. Microglia in the OB of NPC1 mice strongly expressed CX3C chemokine receptor 1 (Cx3cr1), a specific receptor for the neural chemokine C-X3-C motif ligand 1 (Cx3cl1)...
December 2016: Glia
https://www.readbyqxmd.com/read/27651844/are-temporal-differences-in-gdnf-and-nos-isoform-induction-contributors-to-neurodegeneration-a-fluorescence-microscopy-based-study
#13
Marie-Francoise Doursout, Yangyan Liang, Mya C Schiess, Angelica Padilla, Brian J Poindexter, Diane L M Hickson-Bick, Roger J Bick
BACKGROUND: Specific factors in Parkinson's disease have become targets as to their protective and degenerative effects. We have demonstrated that cytokines and PD-CSF detrimentally affect microglia and astrocyte growth. While glial cell-derived neurotrophic factor (GDNF) has been recognized as a possible neuron-rescue agent, nitric oxide synthase (NOS) has been implicated in neurodegenerative processes. OBJECTIVE: To demonstrate that glial cell activation, cytokine production, and NOS induction, play an intimate role in the loss of dopaminergic signaling, via mechanisms that are a result of inflammation and inflammatory stimuli...
2016: Open Neurology Journal
https://www.readbyqxmd.com/read/27629482/evaluation-of-the-potential-effects-of-as03-adjuvanted-a-h1n1-pdm09-vaccine-administration-on-the-central-nervous-system-of-non-primed-and-a-h1n1-pdm09-primed-cotton-rats
#14
Camille Planty, Corey P Mallett, Kevin Yim, Jorge C G Blanco, Marina Boukhvalova, Thomas March, Robbert van der Most, Eric Destexhe
An increased risk of narcolepsy following administration of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine (Pandemrix™) was described in children and adolescents in certain European countries. We investigated the potential effects of administration of the AS03-adjuvanted vaccine, non-adjuvanted vaccine antigen and AS03 Adjuvant System alone, on the central nervous system (CNS) in one-month-old cotton rats. Naïve or A(H1N1)pdm09 virus-primed animals received 2 or 3 intramuscular injections, respectively, of test article or saline at 2-week intervals...
September 14, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27596437/identification-of-a-novel-mechanism-of-blood-brain-communication-during-peripheral-inflammation-via-choroid-plexus-derived-extracellular-vesicles
#15
Sriram Balusu, Elien Van Wonterghem, Riet De Rycke, Koen Raemdonck, Stephan Stremersch, Kris Gevaert, Marjana Brkic, Delphine Demeestere, Valerie Vanhooren, An Hendrix, Claude Libert, Roosmarijn E Vandenbroucke
Here, we identified release of extracellular vesicles (EVs) by the choroid plexus epithelium (CPE) as a new mechanism of blood-brain communication. Systemic inflammation induced an increase in EVs and associated pro-inflammatory miRNAs, including miR-146a and miR-155, in the CSF Interestingly, this was associated with an increase in amount of multivesicular bodies (MVBs) and exosomes per MVB in the CPE cells. Additionally, we could mimic this using LPS-stimulated primary CPE cells and choroid plexus explants...
October 4, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27596278/regulation-of-inflammatory-responses-by-neuregulin-1-in-brain-ischemia-and-microglial-cells-in-vitro-involves-the-nf-kappa-b-pathway
#16
Lauren J Simmons, Monique C Surles-Zeigler, Yonggang Li, Gregory D Ford, Gale D Newman, Byron D Ford
BACKGROUND: We previously demonstrated that neuregulin-1 (NRG-1) was neuroprotective in rats following ischemic stroke. Neuroprotection by NRG-1 was associated with the suppression of pro-inflammatory gene expression in brain tissues. Over-activation of brain microglia can induce pro-inflammatory gene expression by activation of transcriptional regulators following stroke. Here, we examined how NRG-1 transcriptionally regulates inflammatory gene expression by computational bioinformatics and in vitro using microglial cells...
2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27576527/colony-stimulating-factor-1-receptor-blockade-prevents-fractionated-whole-brain-irradiation-induced-memory-deficits
#17
Xi Feng, Timothy D Jopson, Maria Serena Paladini, Sharon Liu, Brian L West, Nalin Gupta, Susanna Rosi
BACKGROUND: Primary central nervous system (CNS) neoplasms and brain metastases are routinely treated with whole-brain radiation. Long-term survival occurs in many patients, but their quality of life is severely affected by the development of cognitive deficits, and there is no treatment to prevent these adverse effects. Neuroinflammation, associated with activation of brain-resident microglia and infiltrating monocytes, plays a pivotal role in loss of neurological function and has been shown to be associated with acute and long-term effects of brain irradiation...
August 30, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27570219/csf-1r-inhibition-attenuates-renal-and-neuropsychiatric-disease-in-murine-lupus
#18
Samantha A Chalmers, Jing Wen, Justine Shum, Jessica Doerner, Leal Herlitz, Chaim Putterman
Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that can affect multiple end organs. Kidney and brain are two of the organs most commonly involved in SLE. Past studies have suggested the importance of macrophages in the pathogenesis of lupus nephritis (LN). Furthermore, as the immune effectors of the brain, microglia have been implicated in pathways leading to neuropsychiatric SLE (NPSLE). We depleted macrophages and microglia using GW2580, a small colony stimulating factor-1 receptor (CSF-1R) kinase inhibitor, in MRL-lpr/lpr (MRL/lpr) mice, a classic murine lupus model that displays features of both LN and NPSLE...
August 25, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27570180/histological-changes-in-the-rat-brain-and-spinal-cord-following-prolonged-intracerebroventricular-infusion-of-cerebrospinal-fluid-from-amyotrophic-lateral-sclerosis-patients-are-similar-to-those-caused-by-the-disease
#19
U Gómez-Pinedo, L Galán, M Yañez, J Matias-Guiu, C Valencia, A Guerrero-Sola, F Lopez-Sosa, J R Brin, M S Benito-Martin, G Leon-Espinosa, A Vela-Souto, C Lendinez, T Guillamon-Vivancos, J A Matias-Guiu, J A Arranz-Tagarro, J A Barcia, A G Garcia
INTRODUCTION: Cerebrospinal fluid (CSF) from amyotrophic lateral sclerosis (ALS) patients induces cytotoxic effects in in vitro cultured motor neurons. MATERIAL AND METHODS: We selected CSF with previously reported cytotoxic effects from 32 ALS patients. Twenty-eight adult male rats were intracerebroventricularly implanted with osmotic mini-pumps and divided into 3 groups: 9 rats injected with CSF from non-ALS patients, 15 rats injected with cytotoxic ALS-CSF, and 4 rats injected with a physiological saline solution...
August 25, 2016: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/27538994/development-and-characterization-of-a-human-microglia-cell-model-of-hiv-1-infection
#20
Pratima Rawat, Stephen A Spector
Microglia cells are the major reservoir of HIV-1 (HIV) within the CNS. However, current models using transformed cell lines are not representative of primary microglia and fetal brain samples for isolation of primary human microglia (HMG) are increasingly difficult to obtain. Here, we describe a monocyte-derived microglia (MMG) cell model of HIV infection that recapitulates infection of primary HMG. CD14(+) cells isolated from healthy donors were cultured with M-CSF, beta-nerve growth factor, GM-CSF, and CCL2, and compared to HMG...
August 18, 2016: Journal of Neurovirology
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