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https://www.readbyqxmd.com/read/29450981/nurr1-promotes-neurogenesis-of-dopaminergic-neuron-and-represses-inflammatory-factors-in-the-transwell-coculture-system-of-neural-stem-cells-and-microglia
#1
Xiaoxiang Chen, Yuan Qian, Xiangpeng Wang, Zhiwei Tang, Jiaotian Xu, Hai Lin, Zhiyong Yang, Xiaobin Song, Di Lu, Jiazhi Guo, Ligong Bian, Yu Li, Lei Zhou, Xingli Deng
INTRODUCTION: Neural stem cells (NSCs) are the most promising cells for cell replacement therapy for Parkinson's disease (PD). However, a majority of the transplanted NSCs differentiated into glial cells, thereby limiting the clinical application. Previous studies indicated that chronic neuroinflammation plays a vital role in the degeneration of midbrain DA (mDA) neurons, which suggested the developing potential of therapies for PD by targeting the inflammatory processes. Thus, Nurr1 (nuclear receptor-related factor 1), a transcription factor, has been referred to play a pivotal role in both the differentiation of dopaminergic neurons in embryonic stages and the maintenance of the dopaminergic phenotype throughout life...
February 15, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29448957/brain-region-specific-enhancement-of-remyelination-and-prevention-of-demyelination-by-the-csf1r-kinase-inhibitor-blz945
#2
Nicolau Beckmann, Elisa Giorgetti, Anna Neuhaus, Stefan Zurbruegg, Nathalie Accart, Paul Smith, Julien Perdoux, Ludovic Perrot, Mark Nash, Sandrine Desrayaud, Peter Wipfli, Wilfried Frieauff, Derya R Shimshek
Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system (CNS). While multiple effective immunomodulatory therapies for MS exist today, they lack the scope of promoting CNS repair, in particular remyelination. Microglia play a pivotal role in regulating myelination processes, and the colony-stimulating factor 1 (CSF-1) pathway is a key regulator for microglia differentiation and survival. Here, we investigated the effects of the CSF-1 receptor kinase inhibitor, BLZ945, on central myelination processes in the 5-week murine cuprizone model by non-invasive and longitudinal magnetic resonance imaging (MRI) and histology...
February 15, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29447138/inflammation-in-the-pathophysiology-of-neuropathic-pain
#3
Claudia Sommer, Mathias Leinders, Nurcan Üçeyler
Peripheral nerve injuries and diseases often lead to pain persisting beyond the resolution of damage, indicating an active disease-promoting process, which may result in chronic pain. This is regarded as a maladaptive mechanism resulting from neuroinflammation that originally serves to promote regeneration and healing. Knowledge on these physiological and pathophysiological processes has accumulated over the last few decades and has started to yield potential therapeutic targets. Key players are macrophages, T-lymphocytes, cytokines, and chemokines...
March 2018: Pain
https://www.readbyqxmd.com/read/29445825/microglial-il-1%C3%AE-progressively-increases-with-duration-of-alcohol-consumption
#4
Bruno Pradier, Edda Erxlebe, Astrid Markert, Ildikó Rácz
Chronic alcohol abuse leads to severe brain damage. Although the underlying neuropathological processes are largely unknown, recent studies show that chronic alcohol consumption leads to neuroinflammation and may result in neurodegeneration and impaired neuronal connectivity. Long-term alcohol consumption promotes the production of pro-inflammatory cytokines, such as TNF-α and IL-1β, and activates microglia cells in the brain. As it has not yet been investigated to what extent these processes dependent on the duration of alcohol consumption or whether microglia are source of pro-inflammatory cytokines in vivo, this study investigated the expression of the pro-inflammatory cytokine, IL-1β, in microglia at different time points in mice chronically exposed to alcohol...
February 14, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29445154/interleukin-4-modulates-microglia-homeostasis-and-attenuates-the-early-slowly-progressive-phase-of-amyotrophic-lateral-sclerosis
#5
Chiara Rossi, Melania Cusimano, Martina Zambito, Annamaria Finardi, Alessia Capotondo, Jose Manuel Garcia-Manteiga, Giancarlo Comi, Roberto Furlan, Gianvito Martino, Luca Muzio
Microglia activation is a commonly pathological hallmark of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), a devastating disorder characterized by a selective motor neurons degeneration. Whether such activation might represent a causal event rather than a secondary epiphenomenon remains elusive. Here, we show that CNS-delivery of IL-4-via a lentiviral-mediated gene therapy strategy-skews microglia to proliferate, inducing these cells to adopt the phenotype of slowly proliferating cells...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29444171/reduced-cognitive-function-increased-blood-brain-barrier-transport-and-inflammatory-responses-and-altered-brain-metabolites-in-ldlr-and-c57bl-6-mice-fed-a-western-diet
#6
Jennifer M Rutkowsky, Linda L Lee, Michelle Puchowicz, Mari S Golub, Douglas E Befroy, Dennis W Wilson, Steven Anderson, Gary Cline, Jason Bini, Kamil Borkowski, Trina A Knotts, John C Rutledge
Recent work suggests that diet affects brain metabolism thereby impacting cognitive function. Our objective was to determine if a western diet altered brain metabolism, increased blood-brain barrier (BBB) transport and inflammation, and induced cognitive impairment in C57BL/6 (WT) mice and low-density lipoprotein receptor null (LDLr -/-) mice, a model of hyperlipidemia and cognitive decline. We show that a western diet and LDLr -/- moderately influence cognitive processes as assessed by Y-maze and radial arm water maze...
2018: PloS One
https://www.readbyqxmd.com/read/29443098/a-novel-in-vitro-live-imaging-assay-of-astrocyte-mediated-phagocytosis-using-ph-indicator-conjugated-synaptosomes
#7
Youkyeong Gloria Byun, Won-Suk Chung
Astrocytes are the major cell type in the brain and directly contact synapses and blood vessels. Although microglial cells have been considered the major immune cells and only phagocytes in the brain, recent studies have shown that astrocytes also participate in various phagocytic processes, such as developmental synapse elimination and clearance of amyloid beta plaques in Alzheimer's disease (AD). Despite these findings, the efficiency of astrocyte engulfment and degradation of their targets is unclear compared with that of microglia...
February 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29429030/nucleoside-reverse-transcriptase-inhibitors-nrtis-induce-pathological-pain-through-wnt5a-mediated-neuroinflammation-in-aging-mice
#8
Subo Yuan, Yuqiang Shi, Kaiwen Guo, Shao-Jun Tang
Highly Active Antiretroviral Therapy (HAART) has significantly contributed to the increase of HIV-infected survivors over 50 years of age. Unfortunately, patients are required to stay on long-term HAART, which may be causally related to the development of neurological problems such as chronic pain. Little is known about the contribution of HAART or its therapeutic agents to the pathogenesis of pain during aging. In this study, we determined the effect of nucleoside reverse transcriptase inhibitors (NRTIs) on the development of mechanical allodynia and the potential underlying mechanism in aging mice (15...
February 10, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29426336/salidroside-provides-neuroprotection-by-modulating-microglial-polarization-after-cerebral-ischemia
#9
Xiangrong Liu, Shaohong Wen, Feng Yan, Kuan Liu, Liqiang Liu, Lei Wang, Shangfeng Zhao, Xunming Ji
BACKGROUND: Following stroke, microglia can be driven to the "classically activated" pro-inflammatory (M1) phenotype and the "alternatively activated" anti-inflammatory (M2) phenotype. Salidroside (SLDS) is known to inhibit inflammation and to possess protective effects in neurological diseases, but to date, the exact mechanisms involved in these processes after stroke have yet to be elucidated. The purpose of this study was to determine the effects of SLDS on neuroprotection and microglial polarization after stroke...
February 9, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29423951/early-calp2-expression-and-microglial-activation-are-potential-inducers-of-spinal-il-6-upregulation-and-bilateral-pain-following-motor-nerve-injury
#10
Shao-Xia Chen, Shao-Kun Wang, Pei-Wen Yao, Guang-Jie Liao, Xiao-Dong Na, Yong-Yong Li, Wei-An Zeng, Xian-Guo Liu, Ying Zang
Previous work from our laboratory showed that motor nerve injury by lumbar 5 ventral root transection (L5-VRT) led to interleukin-6 (IL-6) overexpression in bilateral spinal cord, and that intrathecal administration of IL-6 neutralizing antibody delayed the induction of mechanical allodynia in bilateral hind paws. However, early events and upstream mechanisms underlying spinal IL-6 expression following L5-VRT require elucidation. The model of L5-VRT was used to induce neuropathic pain, which was assessed with von Frey hairs and the plantar tester in adult male Sprague-Dawley rats...
February 9, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29423384/perspectives-in-lipocalin-2-emerging-biomarker-for-medical-diagnosis-and-prognosis-for-alzheimer-s-disease
#11
REVIEW
Juhyun Song, Oh Yoen Kim
Lipocalin-2 (LCN2), a secreted glycoprotein belonging to the lipocalin superfamily was reported to participate in various biological processes including cell migration, cell survival, inflammatory responses, and insulin sensitivity. LCN2 is expressed in the multiple tissues such as kidney, liver, uterus, and bone marrow. The receptors for LCN2 were additionally found in microglia, astrocytes, epithelial cells, and neurons, but the role of LCN2 in the central nervous system (CNS) has not been fully understood yet...
January 2018: Clinical Nutrition Research
https://www.readbyqxmd.com/read/29422055/calcineurin-a-beta-deficiency-ameliorates-hfd-induced-hypothalamic-astrocytosis-in-mice
#12
Katrin Pfuhlmann, Sonja C Schriever, Beata Legutko, Peter Baumann, Luke Harrison, Dhiraj G Kabra, Emily Violette Baumgart, Matthias H Tschöp, Cristina Garcia-Caceres, Paul T Pfluger
ᅟ: Astrocytosis is a reactive process involving cellular, molecular, and functional changes to facilitate neuronal survival, myelin preservation, blood brain barrier function and protective glial scar formation upon brain insult. The overall pro- or anti-inflammatory impact of reactive astrocytes appears to be driven in a context- and disease-driven manner by modulation of astrocytic Ca2+ homeostasis and activation of Ca2+/calmodulin-activated serine/threonine phosphatase calcineurin. Here, we aimed to assess whether calcineurin is dispensable for astrocytosis in the hypothalamus driven by prolonged high fat diet (HFD) feeding...
February 8, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29419657/neuroinflammation-of-the-spinal-cord-and-nerve-roots-in-chronic-radicular-pain-patients
#13
Daniel Albrecht, Shihab Ahmed, Norman Kettner, Ronald Borra, Julien Cohen-Adad, Hao Deng, Timothy Houle, Arissa Opalacz, Sarah Roth, Marcos Vidal Melo, Lucy Chen, Jianren Mao, Jacob Hooker, Marco L Loggia, Yi Zhang
Numerous preclinical studies support the role of spinal neuroimmune activation in the pathogenesis of chronic pain, and targeting glia (e.g., microglia/astrocyte)- or macrophage-mediated neuroinflammatory responses effectively prevents or reverses the establishment of persistent nocifensive behaviors in laboratory animals. However, thus far the translation of those findings into novel treatments for clinical use has been hindered by the scarcity of data supporting the role of neuroinflammation in human pain...
February 5, 2018: Pain
https://www.readbyqxmd.com/read/29417448/atorvastatin-attenuates-cognitive-deficits-and-neuroinflammation-induced-by-a%C3%AE-1-42-involving-modulation-of-tlr4-traf6-nf-%C3%AE%C2%BAb-pathway
#14
Shan Wang, Xiaowei Zhang, Liuyu Zhai, Xiaona Sheng, Weina Zheng, Hongshan Chu, Guohua Zhang
Inflammatory damage aggravates the progression of Alzheimer's disease (AD) and the mechanism of inflammatory damage may provide a new therapeutic window for the treatment of AD. Toll-like receptor 4 (TLR4)-mediated signaling can regulate the inflammatory process. However, changes in TLR4 signaling pathway induced by beta-amyloid (Aβ) have not been well characterized in brain, especially in the hippocampus. In the present study, we explored the changes of TLR4 signaling pathway induced by Aβ in the hippocampus and the role of atorvastatin in modulating this signal pathway and neurotoxicity induced by Aβ...
February 7, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29417177/stem-cells-from-human-apical-papilla-decrease-neuro-inflammation-and-stimulate-oligodendrocyte-progenitor-differentiation-via-activin-a-secretion
#15
Pauline De Berdt, Pauline Bottemanne, John Bianco, Mireille Alhouayek, Anibal Diogenes, Amy Llyod, Jose Gerardo-Nava, Gary A Brook, Véronique Miron, Giulio G Muccioli, Anne des Rieux
Secondary damage following spinal cord injury leads to non-reversible lesions and hampering of the reparative process. The local production of pro-inflammatory cytokines such as TNF-α can exacerbate these events. Oligodendrocyte death also occurs, followed by progressive demyelination leading to significant tissue degeneration. Dental stem cells from human apical papilla (SCAP) can be easily obtained at the removal of an adult immature tooth. This offers a minimally invasive approach to re-use this tissue as a source of stem cells, as compared to biopsying neural tissue from a patient with a spinal cord injury...
February 7, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29416036/a-transcriptomic-atlas-of-aged-human-microglia
#16
Marta Olah, Ellis Patrick, Alexandra-Chloe Villani, Jishu Xu, Charles C White, Katie J Ryan, Paul Piehowski, Alifiya Kapasi, Parham Nejad, Maria Cimpean, Sarah Connor, Christina J Yung, Michael Frangieh, Allison McHenry, Wassim Elyaman, Vlad Petyuk, Julie A Schneider, David A Bennett, Philip L De Jager, Elizabeth M Bradshaw
With a rapidly aging global human population, finding a cure for late onset neurodegenerative diseases has become an urgent enterprise. However, these efforts are hindered by the lack of understanding of what constitutes the phenotype of aged human microglia-the cell type that has been strongly implicated by genetic studies in the pathogenesis of age-related neurodegenerative disease. Here, we establish the set of genes that is preferentially expressed by microglia in the aged human brain. This HuMi_Aged gene set captures a unique phenotype, which we confirm at the protein level...
February 7, 2018: Nature Communications
https://www.readbyqxmd.com/read/29411894/melatonin-attenuated-retinal-neovascularization-and-neuroglial-dysfunction-by-inhibition-of-hif-1%C3%AE-vegf-pathway-in-oxygen-induced-retinopathy-mice
#17
REVIEW
Yue Xu, Xi Lu, Yaguang Hu, Boyu Yang, Ching-Kit Tsui, Shanshan Yu, Lin Lu, Xiaoling Liang
Retinopathy of prematurity (ROP) is a retinopathy characterized by retinal neovascularization (RNV) occurring in preterm infants treated with high concentrations of oxygen and may lead to blindness in severe cases. Currently, anti-VEGF therapy is a major treatment for ROP, but it is costly and may cause serious complications. The previous study has demonstrated that melatonin exerted neuroprotective effect against retinal ganglion cell death induced by hypoxia in neonatal rats. However, whether melatonin is anti-angiogenic and neuroglial protective in the progression of ROP remains unknown...
February 7, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29411111/functional-morphology-of-the-blood-brain-barrier-in-health-and-disease
#18
REVIEW
Stefan Liebner, Rick M Dijkhuizen, Yvonne Reiss, Karl H Plate, Dritan Agalliu, Gabriela Constantin
The adult quiescent blood-brain barrier (BBB), a structure organised by endothelial cells through interactions with pericytes, astrocytes, neurons and microglia in the neurovascular unit, is highly regulated but fragile at the same time. In the past decade, there has been considerable progress in understanding not only the molecular pathways involved in BBB development, but also BBB breakdown in neurological diseases. Specifically, the Wnt/β-catenin, retinoic acid and sonic hedgehog pathways moved into the focus of BBB research...
February 6, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29408508/role-of-lrrk2-in-manganese-induced-neuroinflammation-and-microglial-autophagy
#19
Jiayan Chen, Peng Su, Wenjing Luo, Jingyuan Chen
Overexposure to manganese (Mn) leads to manganism and neurotoxicity induced by Mn is the focus of recent research. Microglia play a vital role in Mn-induced neurotoxicity, and our previous studies firstly showed that Mn could stimulate activation of microglia, leading to the neuroinflammation, and inhibition of microglial inflammation effectively attenuated Mn-induced death of dopamine neurons. However, the detailed mechanism of manganese-induced neuroinflammation is still unclear. Leucine rich repeat kinase 2 (LRRK2) is a key molecule in the pathogenesis of many neurodegenerative disorders...
February 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29408500/microrna-let-7c-5p-improves-neurological-outcomes-in-a-murine-model-of-traumatic-brain-injury-by-suppressing-neuroinflammation-and-regulating-microglial-activation
#20
Jingfang Lv, Yong Zeng, Yu Qian, Jingfei Dong, Zhixiang Zhang, Jianning Zhang
MicroRNAs (miRNAs) are a class of non-coding small RNAs that regulate the expression of target genes. They derive from pre-miRNAs that are enzymatically processed by dicer to ∼22 nucleotide mature miRNAs. Members of the pre-miRNA lethal-7 (let-7) are known to regulate cell proliferation and apoptosis. Here, we showed that the level of let-7c-5p, a key member of the let-7 family, was rapidly reduced in the traumatically injured foci in brains of adult C57BL/6J mice and gradually recovered to the pre-injury level 14 days after traumatic brain injury (TBI) induction...
February 3, 2018: Brain Research
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