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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/27910893/interference-with-protease-activated-receptor-1-alleviates-neuronal-cell-death-induced-by-lipopolysaccharide-stimulated-microglial-cells-through-the-pi3k-akt-pathway
#2
Yuxin Li, Wuyang Yang, Alfredo Quinones-Hinojosa, Baocheng Wang, Shujun Xu, Weijie Zhu, Feng Yu, Shaoji Yuan, Peigang Lu
Excessive microglial cells activation in response to inflammatory stimuli leads to synaptic loss, dysfunction, and neuronal cell death. Activated microglia are involved in the pathogenesis of neurological conditions and frequently contribute to several complications. Accumulating evidence suggests that signaling through PAR-1 is involved in inflammation, however, its function has yet to be fully elucidated. Here, we have demonstrated that the suppression of PAR-1 leads to down-regulation of inflammatory factors including IL-1β, IL-6, TNF-α, NO, as well as the prevention of activation of NF-κB in BV2 cells...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27906951/changes-in-neuroglial-activity-in-multiple-spinal-segments-after-caudal-epidural-pulsed-radiofrequency-in-a-rat-model-of-lumbar-disc-herniation
#3
Hee Kyung Cho, Jae Hoon Kang, So-Yeon Kim, Mi-Jung Choi, Se Jin Hwang, Yun-Woo Cho, Sang-Ho Ahn
BACKGROUND: Herniated lumbar discs can induce sciatica by mechanical compression and/or chemical irritation. It was recently reported that neuroglial cellular activity after pulsed radiofrequency (PRF) application to a single dorsal root ganglion (DRG) attenuated neuroglial activity at the corresponding spinal dorsal horn. Recently, caudal epidural PRF has been used to manage neuropathic pain, but evidence of molecular changes after the administration of caudal epidural PRF to attenuate neuropathic pain is lacking, and it has not been determined whether caudal epidural PRF affects neuroglial activity at different spinal levels...
November 2016: Pain Physician
https://www.readbyqxmd.com/read/27904823/expression-of-gp91phox-and-p22phox-catalytic-subunits-of-nadph-oxidase-on-microglia-in-nasu-hakola-disease-brains
#4
Jun-Ichi Satoh, Yoshihiro Kino, Motoaki Yanaizu, Youhei Tosaki, Kenji Sakai, Tusyoshi Ishida, Yuko Saito
The superoxide-producing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex of phagocytes (phox) plays a key role in production of reactive oxygen species (ROS) by microglia. The catalytic subunits of the NADPH oxidase are composed of p22phox and gp91phox. Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder caused by a loss-of-function mutation of either TYROBP (DAP12) or TREM2. Pathologically, the brains of NHD patients exhibit extensive demyelination designated leukoencephalopathy, astrogliosis, accumulation of axonal spheroids, and remarkable activation of microglia predominantly in the white matter of frontal and temporal lobes...
November 2016: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/27904472/clearing-the-corpses-regulatory-mechanisms-novel-tools-and-therapeutic-potential-of-harnessing-microglial-phagocytosis-in-the-diseased-brain
#5
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/27903933/translocator-positron-emission-tomography-and-magnetic-resonance-spectroscopic-imaging-of-brain-glial-cell-activation-in-multiple-sclerosis
#6
Gourab Datta, Ines R Violante, Gregory Scott, Karl Zimmerman, Andre Santos-Ribeiro, Eugenii A Rabiner, Roger N Gunn, Omar Malik, Olga Ciccarelli, Richard Nicholas, Paul M Matthews
BACKGROUND: Multiple sclerosis (MS) is characterised by a diffuse inflammatory response mediated by microglia and astrocytes. Brain translocator protein (TSPO) positron-emission tomography (PET) and [myo-inositol] magnetic resonance spectroscopy (MRS) were used together to assess this. OBJECTIVE: To explore the in vivo relationships between MRS and PET [(11)C]PBR28 in MS over a range of brain inflammatory burden. METHODS: A total of 23 patients were studied...
November 30, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/27903866/nigral-dopaminergic-pak4-prevents-neurodegeneration-in-rat-models-of-parkinson-s-disease
#7
So-Yoon Won, Mee-Hee Park, Soon-Tae You, Seung-Won Choi, Hyong-Kyu Kim, Catriona McLean, Suk-Chul Bae, Sang Ryong Kim, Byung Kwan Jin, Kun Ho Lee, Eun-Young Shin, Eung-Gook Kim
Parkinson's disease (PD) is characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra. No neuroprotective treatments have successfully prevented the progression of this disease. We report that p21-activated kinase 4 (PAK4) is a key survival factor for DA neurons. We observed PAK4 immunoreactivity in rat and human DA neurons in brain tissue, but not in microglia or astrocytes. PAK4 activity was markedly decreased in postmortem brain tissue from PD patients and in rodent models of PD...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903745/inhibiting-microglia-expansion-prevents-diet-induced-hypothalamic-and-peripheral-inflammation
#8
Caroline André, Omar Guzman-Quevedo, Charlotte Rey, Julie Rémus-Borel, Samantha Clark, Ashley Castellanos-Jankiewicz, Elodie Ladeveze, Thierry Leste-Lasserre, Agnes Nadjar, Djoher Nora Abrous, Sophie Laye, Daniela Cota
Cell proliferation and neuroinflammation in the adult hypothalamus may contribute to the pathogenesis of obesity. Here we tested whether the intertwining of these two processes has a role in the metabolic changes caused by three weeks of saturated high-fat diet (HFD) consumption.As compared to chow, HFD-fed mice rapidly increased body weight and fat mass, and specifically showed increased microglia number in the arcuate nucleus (ARC) of the hypothalamus. Microglia expansion required the adequate presence of fats and carbohydrates in the diet, since feeding mice a very high-fat, very low-carbohydrate diet did not affect cell proliferation...
November 30, 2016: Diabetes
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
#9
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/27903275/cell-cycle-inhibition-reduces-inflammatory-responses-neuronal-loss-and-cognitive-deficits-induced-by-hypobaria-exposure-following-traumatic-brain-injury
#10
Jacob W Skovira, Junfang Wu, Jessica J Matyas, Alok Kumar, Marie Hanscom, Shruti V Kabadi, Raymond Fang, Alan I Faden
BACKGROUND: Traumatic brain injury (TBI) patients in military settings can be exposed to prolonged periods of hypobaria (HB) during aeromedical evacuation. Hypobaric exposure, even with supplemental oxygen to prevent hypoxia, worsens outcome after experimental TBI, in part by increasing neuroinflammation. Cell cycle activation (CCA) after TBI has been implicated as a mechanism contributing to both post-traumatic cell death and neuroinflammation. Here, we examined whether hypobaric exposure in rats subjected to TBI increases CCA and microglial activation in the brain, as compared to TBI alone, and to evaluate the ability of a cyclin-dependent kinase (CDK) inhibitor (CR8) to reduce such changes and improve behavioral outcomes...
December 1, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27902351/protective-role-of-cx3cr1-signaling-in-resident-cells-of-the-central-nervous-system-during-experimental-herpes-simplex-virus-encephalitis
#11
Rafik Menasria, Coraline Canivet, Jocelyne Piret, Jean Gosselin, Guy Boivin
CX3CR1 is an important chemokine receptor expressed on the surface of microglia and blood leukocytes including monocytes. Signaling through this receptor influences the immune activity of microglia and monocytes trafficking into the central nervous system (CNS) in several neurological diseases. During experimental herpes simplex virus 1 (HSV-1) encephalitis (HSE), CX3CR1 deficiency has been reported to exacerbate the outcome of the disease. However, the precise contribution of CX3CR1 expressed in resident cells of the CNS or peripheral monocytes in protection against HSE remains unclear...
November 30, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27900599/melatonin-attenuates-manganese-and-lipopolysaccharide-induced-inflammatory-activation-of-bv2-microglia
#12
Euteum Park, Hong Sung Chun
Melatonin, a naturally occurring neurohormone in the pineal gland, has been shown to exert antioxidant and anti-inflammatory effects. This study examined the effects of melatonin on manganese (Mn) and/or lipopolysaccharide (LPS)-induced microglial activation. Melatonin (10 μM) inhibited Mn (100 μM) and/or LPS (0.5 μg/ml)-induced phagocytotic activity of activated BV2 microglia. It also inhibited the lipid peroxidation and intracellular reduced glutathione (GSH) depletion induced by Mn and/or LPS. Melatonin effectively suppressed the upregulation of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) at both mRNA and protein levels in Mn and/or LPS-stimulated BV2 microglia...
November 30, 2016: Neurochemical Research
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
#13
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/27897273/a-novel-therapeutic-peptide-as-a-partial-agonist-of-rankl-in-ischemic-stroke
#14
Hitomi Kurinami, Munehisa Shimamura, Hironori Nakagami, Hideo Shimizu, Hiroshi Koriyama, Tomohiro Kawano, Kouji Wakayama, Hideki Mochizuki, Hiromi Rakugi, Ryuichi Morishita
The enhanced receptor activator of nuclear factor-κB (NFκB) ligand (RANKL) and its receptor (RANK) signal have been reported to attenuate ischemic brain injury through inhibition of Toll-like receptor (TLR) 4-mediated inflammation. However, augmentation of the RANKL/RANK signal also accelerates osteoporosis, which is a potential problem in clinical use of RANKL. Therefore, we developed novel peptides, microglial healing peptides (MHPs), which were based on the DE and/or EF loop of RANKL. Among them, MHP1 was the most effective inhibitor of TLR4-induced inflammations in microglia/macrophages...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27896432/repression-of-telomere-associated-genes-by-microglia-activation-in-neuropsychiatric-disease
#15
Golo Kronenberg, Ria Uhlemann, Johanna Schöner, Stephanie Wegner, Valérie Boujon, Nikolas Deigendesch, Matthias Endres, Karen Gertz
Microglia senescence may promote neuropsychiatric disease. This prompted us to examine the relationship between microglia activation states and telomere biology. A panel of candidate genes associated with telomere maintenance, mitochondrial biogenesis, and cell-cycle regulation were investigated in M1- and M2-polarized microglia in vitro as well as in MACS-purified CD11b+ microglia/brain macrophages from models of stroke, Alzheimer's disease, and chronic stress. M1 polarization, ischemia, and Alzheimer pathology elicited a strikingly similar transcriptomic profile with, in particular, reduced expression of murine Tert...
November 28, 2016: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/27895165/rats-with-a-missense-mutation-in-atm-display-neuroinflammation-and-neurodegeneration-subsequent-to-accumulation-of-cytosolic-dna-following-unrepaired-dna-damage
#16
Hazel Quek, John Luff, KaGeen Cheung, Sergei Kozlov, Magtouf Gatei, C Soon Lee, Mark C Bellingham, Peter G Noakes, Yi Chieh Lim, Nigel L Barnett, Steven Dingwall, Ernst Wolvetang, Tomoji Mashimo, Tara L Roberts, Martin F Lavin
Mutations in the ataxia-telangiectasia (A-T)-mutated (ATM) gene give rise to the human genetic disorder A-T, characterized by immunodeficiency, cancer predisposition, and neurodegeneration. Whereas a series of animal models recapitulate much of the A-T phenotype, they fail to present with ataxia or neurodegeneration. We describe here the generation of an Atm missense mutant [amino acid change of leucine (L) to proline (P) at position 2262 (L2262P)] rat by intracytoplasmic injection (ICSI) of mutant sperm into oocytes...
November 28, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27894923/therapeutic-implications-of-toll-like-receptors-in-peripheral-neuropathic-pain
#17
REVIEW
Krishan K Thakur, Jyoti Saini, Kanika Mahajan, Dhyanendra Singh, Dinkar P Jaiswal, Srishti Mishra, Anupam Bishyaee, Gautam Sethi, Ajaikumar B Kunnumakkara
Neuropathic pain is a state of chronic pain arising after peripheral or central nerve injury. These injuries can be mediated through the activation of various cells (astrocytes, microglia and Schwann cells), as well as the dissolution of distal axons. Recent studies have suggested that after nerve injury, Toll-like receptors (TLRs) are involved in Wallerian degeneration and generation of neuropathic pain. Furthermore, these TLRs are responsible for the stimulation of astrocytes and microglia that can cause induction of the proinflammatory mediators and cytokines in the spinal cord, thereby leading to the generation and maintenance of neuropathic pain...
November 25, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27894396/ellagic-acid-ameliorates-cuprizone-induced-acute-cns-inflammation-via-restriction-of-microgliosis-and-down-regulation-of-ccl2-and-ccl3-pro-inflammatory-chemokines
#18
N Sanadgol, F Golab, A Mostafaie, M Mehdizadeh, M Abdollahi, M Sharifzadeh, H Ravan
Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuro-inflammatory conditions. Microglia making the innate immune system of the central nervous system (CNS) and are imperative cellular mediators of neuro-inflammatory processes. In this study, neuro-protective effects of EA on cuprizone (Cup)-induced acute CNS inflammation evaluated. C57BL/6J mice were fed with chow containing 0.2 % Cup for 3 weeks to induce acute neuro-inflammation predominantly in the corpus callosum (CC)...
October 31, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27894304/brain-inflammation-is-accompanied-by-peripheral-inflammation-in-cstb-mice-a-model-for-progressive-myoclonus-epilepsy
#19
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
#20
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
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