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https://www.readbyqxmd.com/read/28183245/ykl-40-as-a-potential-biomarker-and-a-possible-target-in-therapeutic-strategies-of-alzheimer-s-disease
#1
Paweł Muszyński, Magdalena Groblewska, Agnieszka Kulczyńska-Przybik, Alina Kułakowska, Barbara Mroczko
BACKGROUND: Growing body of evidence suggests that pathogenesis of Alzheimer's disease (AD), a progressing neurodegenerative condition, is not limited to the neuronal compartment, but also involves various immunological mechanisms. Insoluble Aβ aggregates in the brain can induce the activation of microglia, resulting in synthesis of proinflammatory mediators, which further can stimulate astrocytic expression of YKL-40. Therefore, the aim of the current review is to present up-to-date data about the role of YKL-40 as a biomarker of AD as well as the possibility of therapeutic strategies targeting neuroinflammation...
February 8, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28177105/the-circumventricular-organs
#2
REVIEW
Charanjit Kaur, Eng-Ang Ling
The circumventricular organs (CVOs) are midline structures located around the third and fourth ventricles and are characterized by a lack of blood-brain barrier. The pineal gland, median eminence, neurohypophysis and the subcommisural organ are classified as secretory, whereas the subfornical organ, area postrema and the organum vasculosum of the lamina terminalis are the sensory CVOs. Specialised ependymal cells known as tanycytes form the ependymal of these organs. Glial cells consisting of astrocytes and microglia/macrophages are present in all these organs...
February 8, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28159556/activated-microglia-trigger-inflammasome-activation-and-lysosomal-destabilization-in-human-rpe-cells
#3
Christopher Nebel, Alexander Aslanidis, Khalid Rashid, Thomas Langmann
Activation of the innate immune system plays a major role in retinal degenerative diseases including age-related macular degeneration (AMD). In this study, we investigated whether reactive microglia trigger and sustain NLRP3 inflammasome activation in human retinal pigment epithelium (ARPE-19) cells. Specifically, we analyzed the potential of cell culture supernatants from lipopolysaccharide (LPS)-stimulated human microglia in combination with the lysosomal destabilization agent Leu-Leu-O-Me (LLOMe) to activate the inflammasome in ARPE-19 cells...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28153013/effects-of-dexamethasone-and-meloxicam-on-borrelia-burgdorferi-induced-inflammation-in-glial-and-neuronal-cells-of-the-central-nervous-system
#4
Geeta Ramesh, Alejandra N Martinez, Dale S Martin, Mario T Philipp
BACKGROUND: Lyme neuroborreliosis (LNB), caused by the spirochete Borrelia burgdorferi (Bb), affects both the central and peripheral nervous systems. Previously, we reported that in a model of acute LNB in rhesus monkeys, treatment with the anti-inflammatory drug dexamethasone significantly reduced both pleocytosis and levels of cerebrospinal fluid (CSF) immune mediators that were induced by Bb. Dexamethasone also inhibited the formation of inflammatory, neurodegenerative, and demyelinating lesions in the brain and spinal cord of these animals...
February 2, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28137632/generation-6-hydroxyl-pamam-dendrimers-improve-cns-penetration-from-intravenous-administration-in-a-large-animal-brain-injury-model
#5
Fan Zhang, J Trent Magruder, Yi-An Lin, Todd C Crawford, Joshua C Grimm, Christopher M Sciortino, Mary Ann Wilson, Mary E Blue, Sujatha Kannan, Michael V Johnston, William A Baumgartner, Rangaramanujam M Kannan
Hypothermic circulatory arrest (HCA) provides neuroprotection during cardiac surgery but entails an ischemic period that can lead to excitotoxicity, neuroinflammation, and subsequent neurologic injury. Hydroxyl polyamidoamine (PAMAM) dendrimers target activated microglia and damaged neurons in the injured brain, and deliver therapeutics in small and large animal models. We investigated the effect of dendrimer size on brain uptake and explored the pharmacokinetics in a clinically-relevant canine model of HCA-induced brain injury...
January 27, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28128358/galectin-3-released-in-response-to-traumatic-brain-injury-acts-as-an-alarmin-orchestrating-brain-immune-response-and-promoting-neurodegeneration
#6
Ping Kei Yip, Alejandro Carrillo-Jimenez, Paul King, Anna Vilalta, Koji Nomura, Chi Cheng Chau, Alexander Michael Scott Egerton, Zhuo-Hao Liu, Ashray Jayaram Shetty, Jordi L Tremoleda, Meirion Davies, Tomas Deierborg, John V Priestley, Guy Charles Brown, Adina Teodora Michael-Titus, Jose Luis Venero, Miguel Angel Burguillos
Traumatic brain injury (TBI) is currently a major cause of morbidity and poor quality of life in Western society, with an estimate of 2.5 million people affected per year in Europe, indicating the need for advances in TBI treatment. Within the first 24 h after TBI, several inflammatory response factors become upregulated, including the lectin galectin-3. In this study, using a controlled cortical impact (CCI) model of head injury, we show a large increase in the expression of galectin-3 in microglia and also an increase in the released form of galectin-3 in the cerebrospinal fluid (CSF) 24 h after head injury...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28125674/characterisation-of-immune-and-neuroinflammatory-changes-associated-with-chemotherapy-induced-peripheral-neuropathy
#7
Preet G S Makker, Samuel S Duffy, Justin G Lees, Chamini J Perera, Ryan S Tonkin, Oleg Butovsky, Susanna B Park, David Goldstein, Gila Moalem-Taylor
Chemotherapy-induced peripheral neuropathy (CIPN) and associated neuropathic pain is a debilitating adverse effect of cancer treatment. Current understanding of the mechanisms underpinning CIPN is limited and there are no effective treatment strategies. In this study, we treated male C57BL/6J mice with 4 cycles of either Paclitaxel (PTX) or Oxaliplatin (OXA) over a week and tested pain hypersensitivity and changes in peripheral immune responses and neuroinflammation on days 7 and 13 post 1st injection. We found that both PTX and OXA caused significant mechanical allodynia...
2017: PloS One
https://www.readbyqxmd.com/read/28086931/the-release-and-trans-synaptic-transmission-of-tau-via-exosomes
#8
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-macrophage-colony-stimulating-factor-1-receptors
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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