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https://www.readbyqxmd.com/read/27912057/gut-microbiota-regulate-motor-deficits-and-neuroinflammation-in-a-model-of-parkinson-s-disease
#1
Timothy R Sampson, Justine W Debelius, Taren Thron, Stefan Janssen, Gauri G Shastri, Zehra Esra Ilhan, Collin Challis, Catherine E Schretter, Sandra Rocha, Viviana Gradinaru, Marie-Francoise Chesselet, Ali Keshavarzian, Kathleen M Shannon, Rosa Krajmalnik-Brown, Pernilla Wittung-Stafshede, Rob Knight, Sarkis K Mazmanian
The intestinal microbiota influence neurodevelopment, modulate behavior, and contribute to neurological disorders. However, a functional link between gut bacteria and neurodegenerative diseases remains unexplored. Synucleinopathies are characterized by aggregation of the protein α-synuclein (αSyn), often resulting in motor dysfunction as exemplified by Parkinson's disease (PD). Using mice that overexpress αSyn, we report herein that gut microbiota are required for motor deficits, microglia activation, and αSyn pathology...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27904472/clearing-the-corpses-regulatory-mechanisms-novel-tools-and-therapeutic-potential-of-harnessing-microglial-phagocytosis-in-the-diseased-brain
#2
REVIEW
Irune Diaz-Aparicio, Sol Beccari, Oihane Abiega, Amanda Sierra
Apoptosis is a widespread phenomenon that occurs in the brain in both physiological and pathological conditions. Dead cells must be quickly removed to avoid the further toxic effects they exert in the parenchyma, a process executed by microglia, the brain professional phagocytes. Although phagocytosis is critical to maintain tissue homeostasis, it has long been either overlooked or indirectly assessed based on microglial morphology, expression of classical activation markers, or engulfment of artificial phagocytic targets in vitro...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27903721/cross-talk-between-brain-innate-immunity-and-serotonin-signaling-underlies-depressive-like-behavior-induced-by-alzheimer-s-amyloid-%C3%AE-oligomers-in-mice
#3
Jose Henrique Ledo, Estefania P Azevedo, Danielle Beckman, Felipe C Ribeiro, Luis E Santos, Daniela S Razolli, Grasielle C Kincheski, Helen M Melo, Maria Bellio, Antonio L Teixeira, Licio A Velloso, Debora Foguel, Fernanda G De Felice, Sergio T Ferreira
: Considerable clinical and epidemiological evidence links Alzheimer's disease (AD) and depression. However, the molecular mechanisms underlying this connection are largely unknown. We reported recently that soluble Aβ oligomers (AβOs), toxins that accumulate in AD brains and are thought to instigate synapse damage and memory loss, induce depressive-like behavior in mice. Here, we report that the mechanism underlying this action involves AβO-induced microglial activation, aberrant TNF-α signaling, and decreased brain serotonin levels...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27899315/injury-stimulated-sonic-hedgehog-expression-in-microglia-contributes-to-neuroinflammatory-response-in-the-mptp-model-of-parkinson-s-disease
#4
Jung Hwi Lee, Young Cheul Chung, Eugene Bok, Hankyu Lee, Sue Hee Huh, Ji Eun Lee, Byung Kwan Jin, Hyuk Wan Ko
Parkinson's disease (PD) is a progressive neurodegenerative disorder in which dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) region are selectively destroyed. Sonic hedgehog (Shh) has been well known to play a key role in a variety of processes such as embryogenesis, cell proliferation and protection, and tissue repair during inflammation. However, the evidences for the innate role of Shh in adult brain injury are presently lacking and studies have been needed to unveil the importance of Shh in the process of neurodegeneration...
November 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27894304/brain-inflammation-is-accompanied-by-peripheral-inflammation-in-cstb-mice-a-model-for-progressive-myoclonus-epilepsy
#5
Olesya Okuneva, Zhilin Li, Inken Körber, Saara Tegelberg, Tarja Joensuu, Li Tian, Anna-Elina Lehesjoki
Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessively inherited childhood-onset neurodegenerative disorder, characterized by myoclonus, seizures, and ataxia. Mutations in the cystatin B gene (CSTB) underlie EPM1. The CSTB-deficient (Cstb (-/-) ) mouse model recapitulates key features of EPM1, including myoclonic seizures. The mice show early microglial activation that precedes seizure onset and neuronal loss and leads to neuroinflammation. We here characterized the inflammatory phenotype of Cstb (-/-) mice in more detail...
November 28, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27893897/imaging-of-glial-cell-activation-and-white-matter-integrity-in-brains-of-active-and-recently-retired-national-football-league-players
#6
Jennifer M Coughlin, Yuchuan Wang, Il Minn, Nicholas Bienko, Emily B Ambinder, Xin Xu, Matthew E Peters, John W Dougherty, Melin Vranesic, Soo Min Koo, Hye-Hyun Ahn, Merton Lee, Chris Cottrell, Haris I Sair, Akira Sawa, Cynthia A Munro, Christopher J Nowinski, Robert F Dannals, Constantine G Lyketsos, Michael Kassiou, Gwenn Smith, Brian Caffo, Susumu Mori, Tomas R Guilarte, Martin G Pomper
Importance: Microglia, the resident immune cells of the central nervous system, play an important role in the brain's response to injury and neurodegenerative processes. It has been proposed that prolonged microglial activation occurs after single and repeated traumatic brain injury, possibly through sports-related concussive and subconcussive injuries. Limited in vivo brain imaging studies months to years after individuals experience a single moderate to severe traumatic brain injury suggest widespread persistent microglial activation, but there has been little study of persistent glial cell activity in brains of athletes with sports-related traumatic brain injury...
November 28, 2016: JAMA Neurology
https://www.readbyqxmd.com/read/27889907/activation-of-nur77-in-microglia-attenuates-proinflammatory-mediators-production-and-protects-dopaminergic-neurons-from-inflammation-induced-cell-death
#7
Tian-Ya Liu, Xiao-Ying Yang, Long-Tai Zheng, Guang-Hui Wang, Xue-Chu Zhen
Microglia-mediated neuroinflammation plays a critical role in the pathological development of Parkinson's disease (PD). Orphan nuclear receptor Nur77 (Nur77) is abundant in neurons, while its role in microglia-mediated neuroinflammation remains unclear. The present data demonstrated that the expression of Nur77 in microglia was reduced accompanied with microglia activation in response to lipopolysaccharide (LPS) in vitro and in experimental MPTP-PD mouse model. Nur77 overexpression or application of Nur77 agonist CsnB suppressed the expression of proinflammatory genes, such as iNOS, COX-2, IL-1β, and TNF-α in the activated microglia, while silenced Nur77 exaggerated the inflammatory responses in microglia...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27888531/fate-of-microglia-during-hiv-1-infection-from-activation-to-senescence
#8
REVIEW
Natalie C Chen, Andrea T Partridge, Christian Sell, Claudio Torres, Julio Martín-García
Microglia support productive human immunodeficiency virus type 1 (HIV-1) infection and disturbed microglial function could contribute to the development of HIV-associated neurocognitive disorders (HAND). Better understanding of how HIV-1 infection and viral protein exposure modulate microglial function during the course of infection could lead to the identification of novel therapeutic targets for both the eradication of HIV-1 reservoir and treatment of neurocognitive deficits. This review first describes microglial origins and function in the normal central nervous system (CNS), and the changes that occur during aging...
November 26, 2016: Glia
https://www.readbyqxmd.com/read/27888296/toll-like-receptor-2-is-increased-in-neurons-in-parkinson-s-disease-brain-and-may-contribute-to-alpha-synuclein-pathology
#9
Nicolas Dzamko, Amanda Gysbers, Gayathri Perera, Anita Bahar, Amrita Shankar, Jianqun Gao, YuHong Fu, Glenda M Halliday
Inflammation is likely a key contributor to the pathogenesis of Parkinson's disease (PD), a progressively debilitating neurodegenerative disease that is accompanied by a pathological accumulation of the α-synuclein protein in a staged manner through the brain. What leads to the accumulation of α-synuclein in PD and how this relates to inflammatory pathways, however, is not entirely clear. Toll-like receptor (TLR) signaling is a major pathway mediating inflammation and, in particular, TLR2 is increasingly being implicated in PD...
November 25, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27882228/oxymatrine-inhibits-microglia-activation-via-hsp60-tlr4-signaling
#10
Feijia Ding, Yunhong Li, Xiaolin Hou, Rui Zhang, Shuting Hu, Yin Wang
Oxymatrine (OMT) is an alkaloid extracted from Sophora flavescens, which has broad anti-inflammatory, antitumor and immunosuppressant actions. However, the underlying molecular mechanisms have remained elusive. Heat shock protein 60 (HSP60) has recently been shown to have an important role in autoimmune reactions. The present study aimed to investigate whether OMT exerts its anti-inflammatory effects by inhibiting microglial activation and examined the role of HSP60 in this process. Western blot analysis and ELISA showed that OMT decreased the expression and release of HSP60 by LPS-activated BV2 cells...
November 2016: Biomedical Reports
https://www.readbyqxmd.com/read/27881137/balancing-the-immune-response-in-the-brain-il-10-and-its-regulation
#11
REVIEW
Diogo Lobo-Silva, Guilhermina M Carriche, A Gil Castro, Susana Roque, Margarida Saraiva
BACKGROUND: The inflammatory response is critical to fight insults, such as pathogen invasion or tissue damage, but if not resolved often becomes detrimental to the host. A growing body of evidence places non-resolved inflammation at the core of various pathologies, from cancer to neurodegenerative diseases. It is therefore not surprising that the immune system has evolved several regulatory mechanisms to achieve maximum protection in the absence of pathology. MAIN BODY: The production of the anti-inflammatory cytokine interleukin (IL)-10 is one of the most important mechanisms evolved by many immune cells to counteract damage driven by excessive inflammation...
November 24, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27880767/distribution-of-misfolded-prion-protein-seeding-activity-alone-does-not-predict-regions-of-neurodegeneration
#12
James Alibhai, Richard A Blanco, Marcelo A Barria, Pedro Piccardo, Byron Caughey, V Hugh Perry, Tom C Freeman, Jean C Manson
Protein misfolding is common across many neurodegenerative diseases, with misfolded proteins acting as seeds for "prion-like" conversion of normally folded protein to abnormal conformations. A central hypothesis is that misfolded protein accumulation, spread, and distribution are restricted to specific neuronal populations of the central nervous system and thus predict regions of neurodegeneration. We examined this hypothesis using a highly sensitive assay system for detection of misfolded protein seeds in a murine model of prion disease...
November 2016: PLoS Biology
https://www.readbyqxmd.com/read/27875748/piperine-attenuates-lipopolysaccharide-lps-induced-inflammatory-responses-in-bv2-microglia
#13
Chen Wang-Sheng, An Jie, Li Jian-Jun, Hong Lan, Xing Zeng-Bao, Li Chang-Qing
Piperine, the chief alkaloid isolated from Piper nigrum, has been known to have anti-inflammatory effect. However, the effects of piperine on neuroinflammation have not been reported. In the present study, we evaluated the effects of piperine on neuroinflammation in BV2 microglia and investigated the molecular mechanism. The results showed that piperine significantly inhibited LPS-induced TNF-α, IL-6, IL-1β, and PGE2 production in BV2 cells. Western blot analysis showed that piperine dose-dependently inhibited LPS-induced NF-κB activation...
November 19, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27863488/mathematical-model-on-alzheimer-s-disease
#14
Wenrui Hao, Avner Friedman
BACKGROUND: Alzheimer disease (AD) is a progressive neurodegenerative disease that destroys memory and cognitive skills. AD is characterized by the presence of two types of neuropathological hallmarks: extracellular plaques consisting of amyloid β-peptides and intracellular neurofibrillary tangles of hyperphosphorylated tau proteins. The disease affects 5 million people in the United States and 44 million world-wide. Currently there is no drug that can cure, stop or even slow the progression of the disease...
November 18, 2016: BMC Systems Biology
https://www.readbyqxmd.com/read/27862694/mesenchymal-stem-cell-derived-microvesicles-modulate-lps-induced-inflammatory-responses-to-microglia-cells
#15
Yarúa Jaimes, Yahaira Naaldijk, Kerstin Wenk, Christiane Leovsky, Frank Emmrich
Microglia cells are the central nervous system immune cells and have been pointed out as the main mediators of the inflammation leading to neurodegenerative disorders. Mesenchymal stromal cells (MSCs) are a heterogeneous population of cells with very high self-renewal properties and uncomplicated in vitro culture. Research has shown that MSCs have the capacity to induce tissue regeneration and reduce inflammation. Studies demonstrated that MSCs have complex paracrine machineries involving shedding of cell-derived microvesicles (MVs), which entail part of the regulatory and regenerative activity of MSCs, as observed in animal models...
November 16, 2016: Stem Cells
https://www.readbyqxmd.com/read/27862631/microglia-show-altered-morphology-and-reduced-arborisation-in-human-brain-during-aging-and-alzheimer-s-disease
#16
Danielle S Davies, Jolande Ma, Thuvarahan Jegathees, And Claire Goldsbury
Changes in microglia function are involved in Alzheimer's disease (AD) for which ageing is the major risk factor. We evaluated microglial cell process morphologies and their grey matter coverage (arborized area) during ageing and in the presence and absence of AD pathology in autopsied human neocortex. Microglial cell processes were reduced in length, showed less branching and reduced arborized area with aging (case range 52-98 yrs). This occurred during normal ageing and without microglia dystrophy or changes in cell density...
November 14, 2016: Brain Pathology
https://www.readbyqxmd.com/read/27858314/genetically-dissecting-p2rx7-expression-within-the-central-nervous-system-using-conditional-humanized-mice
#17
Michael W Metzger, Sandra M Walser, Fernando Aprile-Garcia, Nina Dedic, Alon Chen, Florian Holsboer, Eduardo Arzt, Wolfgang Wurst, Jan M Deussing
The purinergic P2X7 receptor (P2X7R) has attracted considerable interest as a potential target for various central nervous system (CNS) pathologies including affective and neurodegenerative disorders. To date, the distribution and cellular localization of the P2X7R in the brain are not fully resolved and a matter of debate mainly due to the limitations of existing tools. However, this knowledge should be a prerequisite for understanding the contribution of the P2X7R to brain disease. Here, we generated a genetic mouse model by humanizing the P2X7R in the mouse as mammalian model organism...
November 17, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27855618/scutellarin-as-a-therapeutic-agent-in-microglia-mediated-neuroinflammation-in-cerebral-ischemia
#18
Chun-Yun Wu, Ming Fang, Aparna Karthikeyan, Yun Yuan, Eng-Ang Ling
Neuroinflammation plays an important role in different brain diseases including acute brain injuries such as cerebral ischemic stroke and chronic neurodegenerative diseases e.g. Alzheimer's disease etc. The central player in this is the activated microglia which produce substantial amounts of proinflammatory mediators that may exacerbate the disease. Associated with microglia activation is astrogliosis characterized by hypertrophic astrocytes with increased expression of proinflammatory cytokines, neurotrophic factors, stem cell, neuronal and proliferation markers, all these are crucial for reconstruction of damaged tissue and ultimate restoration of neurological functions...
November 18, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27853976/tapered-tip-capillary-electrophoresis-nano-electrospray-ionization-mass-spectrometry-for-ultrasensitive-proteomics-the-mouse-cortex
#19
Sam B Choi, Marta Zamarbide, M Chiara Manzini, Peter Nemes
Ultrasensitive characterization of the proteome raises the potential to understand how differential gene expression orchestrates cell heterogeneity in the brain. Here, we report a microanalytical capillary electrophoresis nano-flow electrospray ionization (CE-nanoESI) interface for mass spectrometry to enable the measurement of limited amounts of proteins in the mouse cortex. Our design integrates a custom-built CE system to a tapered-tip metal emitter in a co-axial sheath-flow configuration. This interface can be constructed in <15 min using readily available components, facilitating broad adaptation...
November 16, 2016: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/27853421/transient-developmental-purkinje-cell-axonal-torpedoes-in-healthy-and-ataxic-mouse-cerebellum
#20
Lovisa Ljungberg, Daneck Lang-Ouellette, Angela Yang, Sriram Jayabal, Sabrina Quilez, Alanna J Watt
Information is carried out of the cerebellar cortical microcircuit via action potentials propagated along Purkinje cell axons. In several human neurodegenerative diseases, focal axonal swellings on Purkinje cells - known as torpedoes - have been associated with Purkinje cell loss. Interestingly, torpedoes are also reported to appear transiently during development in rat cerebellum. The function of Purkinje cell axonal torpedoes in health as well as in disease is poorly understood. We investigated the properties of developmental torpedoes in the postnatal mouse cerebellum of wild-type and transgenic mice...
2016: Frontiers in Cellular Neuroscience
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