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https://www.readbyqxmd.com/read/28645622/in-vivo-effects-of-knocking-down-metabotropic-glutamate-receptor-5-in-the-sod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis
#1
Tiziana Bonifacino, Luca Cattaneo, Elena Gallia, Aldamaria Puliti, Marcello Melone, Francesca Provenzano, Simone Bossi, Ilaria Musante, Cesare Usai, Fiorenzo Conti, Giambattista Bonanno, Marco Milanese
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder due to loss of upper and lower motor neurons (MNs). The mechanisms of neuronal death are largely unknown, thus prejudicing the successful pharmacological treatment. One major cause for MN degeneration in ALS is represented by glutamate(Glu)-mediated excitotoxicity. We have previously reported that activation of Group I metabotropic Glu receptors (mGluR1 and mGluR5) at glutamatergic spinal cord nerve terminals produces abnormal Glu release in the widely studied SOD1(G93A) mouse model of ALS...
June 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28644409/quercetin-protects-obesity-induced-hypothalamic-inflammation-by-reducing-microglia-mediated-inflammatory-responses-via-ho-1-induction
#2
Jihyeon Yang, Chu-Sook Kim, Thai Hien Tu, Min-Seon Kim, Tsuyoshi Goto, Teruo Kawada, Myung-Sook Choi, Taesun Park, Mi-Kyung Sung, Jong Won Yun, Suck-Young Choe, Jee Hye Lee, Yeonsoo Joe, Hye-Seon Choi, Sung Hoon Back, Hun Taeg Chung, Rina Yu
Obesity-induced hypothalamic inflammation is characterized by activation of microglia, which are resident macrophages of the central nervous system, and is implicated in the derangement of energy homeostasis, metabolic complications, and neurodegenerative diseases. Quercetin, a naturally occurring flavonoid, is known to protect against oxidative stress and inflammation-related metabolic complications. Here, we demonstrate that quercetin reduces obesity-induced hypothalamic inflammation by inhibiting microglia-mediated inflammatory responses, and the beneficial action of quercetin is associated with heme oxygenase (HO-1) induction...
June 23, 2017: Nutrients
https://www.readbyqxmd.com/read/28640632/gut-microbiota-nitric-oxide-and-microglia-as-pre-requisites-for-neurodegenerative-disorders
#3
Joyce Ka Yu Tse
Regulating fluctuating endogenous nitric oxide (NO) levels is necessary for proper physiological functions. Aberrant NO pathways are implicated in a number of neurological disorders, including Alzheimer's Disease (AD) and Parkinson's Disease. The mechanism of NO in oxidative and nitrosative stress with pathological consequences involves reactions with reactive oxygen species (e.g. superoxide) to form the highly reactive peroxynitrite, hydrogen peroxide, hypochloride ions and hydroxyl radical. NO levels are typically regulated by endogenous nitric oxide synthases (NOS), and inflammatory iNOS is implicated in the pathogenesis of neurodegenerative diseases, in which elevated NO mediates axonal degeneration and activates cyclooxygenases to provoke neuroinflammation...
June 22, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28638339/nutritional-and-pharmacological-strategies-to-regulate-microglial-polarization-in-cognitive-aging-and-alzheimer-s-disease
#4
REVIEW
Emiliano Peña-Altamira, Sabrina Petralla, Francesca Massenzio, Marco Virgili, Maria L Bolognesi, Barbara Monti
The study of microglia, the immune cells of the brain, has experienced a renaissance after the discovery of microglia polarization. In fact, the concept that activated microglia can shift into the M1 pro-inflammatory or M2 neuroprotective phenotypes, depending on brain microenvironment, has completely changed the understanding of microglia in brain aging and neurodegenerative diseases. Microglia polarization is particularly important in aging since an increased inflammatory status of body compartments, including the brain, has been reported in elderly people...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28637381/role-of-caspase-3-mediated-apoptosis-in-chronic-caspase-3-cleaved-tau-accumulation-and-blood-brain-barrier-damage-in-the-corpus-callosum-after-traumatic-brain-injury-in-rats
#5
Olena Glushakova, Andriy O Glushakov, Cesar Borlongan, Alex Valadka, Ronald L Hayes, Alexander V Glushakov
Traumatic brain injury (TBI) may be a significant risk factor for development of neurodegenerative disorders such as chronic traumatic encephalopathy (CTE), post-traumatic epilepsy (PTE), and Alzheimer's (AD) and Parkinson's (PD) diseases. Chronic TBI is associated with several pathological features that are also characteristic of neurodegenerative diseases, including tau pathologies, caspase-3-mediated apoptosis, neuroinflammation, and microvascular alterations. The goal of this study was to evaluate changes following TBI in cleaved-caspase-3 and caspase-3-cleaved tau truncated at Asp421 and their relationships to cellular markers potentially associated with inflammation and blood-brain (BBB) barrier damage...
June 22, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28637354/essential-dietary-bioactive-lipids-in-neuroinflammatory-diseases
#6
M Valeria Catani, Valeria Gasperi, Tiziana Bisogno, Mauro Maccarrone
Under physiological conditions, neurons and glia are in a healthy, redox-balanced environment; when injury perturbs this equilibrium, a neuroinflammatory state is established by activated microglia that triggers pro-inflammatory responses and alters the oxidant/antioxidant balance, thus leading to neuronal loss and neurodegeneration. In neurodegenerative diseases (such as Alzheimer's disease, Parkinson's disease, amyothrophic lateral sclerosis, and multiple sclerosis), the brain is in a constitutively self-sustaining cycle of inflammation and oxidative stress that prompts and amplifies brain damage...
June 22, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28633046/macrophages-with-cellular-backpacks-for-targeted-drug-delivery-to-the-brain
#7
Natalia L Klyachko, Roberta Polak, Matthew J Haney, Yuling Zhao, Reginaldo J Gomes Neto, Michael C Hill, Alexander V Kabanov, Robert E Cohen, Michael F Rubner, Elena V Batrakova
Most potent therapeutics are unable to cross the blood-brain barrier following systemic administration, which necessitates the development of unconventional, clinically applicable drug delivery systems. With the given challenges, biologically active vehicles are crucial to accomplishing this task. We now report a new method for drug delivery that utilizes living cells as vehicles for drug carriage across the blood brain barrier. Cellular backpacks, 7-10 μm diameter polymer patches of a few hundred nanometers in thickness, are a potentially interesting approach, because they can act as drug depots that travel with the cell-carrier, without being phagocytized...
June 17, 2017: Biomaterials
https://www.readbyqxmd.com/read/28624264/profiling-of-cytosolic-and-mitochondrial-h2o2-production-using-the-h2o2-sensitive-protein-hyper-in-lps-induced-microglia-cells
#8
Junghyung Park, Seunghoon Lee, Hyun-Shik Lee, Sang-Rae Lee, Dong-Seok Lee
Dysregulation of the production of pro-inflammatory mediators in microglia exacerbates the pathologic process of neurodegenerative disease. ROS actively affect microglia activation by regulating transcription factors that control the expression of pro-inflammatory genes. However, accurate information regarding the function of ROS in different subcellular organelles has not yet been established. Here, we analyzed the pattern of cytosolic and mitochondrial H2O2 formation in LPS-activated BV-2 microglia using the H2O2-sensitive protein HyPer targeted to specific subcellular compartments...
June 15, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28624208/safe-and-efficient-silencing-with-a-pol-ii-but-not-a-pol-lii-promoter-expressing-an-artificial-mirna-targeting-human-huntingtin
#9
Edith L Pfister, Kathryn O Chase, Huaming Sun, Lori A Kennington, Faith Conroy, Emily Johnson, Rachael Miller, Florie Borel, Neil Aronin, Christian Mueller
Huntington's disease is a devastating, incurable neurodegenerative disease affecting up to 12 per 100,000 patients worldwide. The disease is caused by a mutation in the Huntingtin (Htt) gene. There is interest in reducing mutant Huntingtin by targeting it at the mRNA level, but the maximum tolerable dose and long-term effects of such a treatment are unknown. Using a self-complementary AAV9 vector, we delivered a mir-155-based artificial miRNA under the control of the chicken β-actin or human U6 promoter. In mouse brain, the artificial miRNA reduced the human huntingtin mRNA by 50%...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623716/aldose-reductase-inhibitors-attenuate-%C3%AE-amyloid-induced-tnf-%C3%AE-production-in-microlgia-via-ros-pkc-mediated-nf-%C3%AE%C2%BAb-and-mapk-pathways
#10
Xiao-Min Song, Qian Yu, Xin Dong, Hyun Ok Yang, Ke-Wu Zeng, Jun Li, Peng-Fei Tu
Microglia-mediated neuroinflammation is a key risk factor to the development of Alzheimer' disease (AD). Aldose reductase (AR) has been found to be widely involved in inflammation-related diseases; however, whether aldose reductase inhibitors (ARIs) could be used to treat neuroinflammation is rarely reported. This study aims to evaluate the anti-neuroinflammatory effects of two major ARIs of Sorbinil (Sor) and Zopolrestat (Zol) in β-amyloid protein (Aβ)-induced microglia (BV-2). We find that Sor and Zol significantly inhibit TNF-α, IL-1β, IL-6 production from microglia in response to Aβ stimulation...
June 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28623715/diosgenin-glucoside-provides-neuroprotection-by-regulating-microglial-m1-polarization
#11
Shaoxia Wang, Fujiang Wang, Hongyun Yang, Ruilin Li, Hong Guo, Limin Hu
The selective suppression of inflammatory factors in activated microglia, rather than totally inhibiting their activation, might be an effective means of slowing the progression of certain neurodegenerative diseases. Diosgenin glucoside (Dios) is a saponin compound extracted from Tritulus terrestris L. We found that Dios suppressed the synthesis of molecules that promote inflammation (M1 markers, such as NO, IL-6, and TNF-α) in rat microglia and BV-2 cells induced with lipopolysaccharides (LPS). In contrast, Dios had no effects on the cellular production of anti-inflammatory factors (M2 markers, such as IL-10, IL-1Rα and CD206) in LPS and IL-4 treated microglia...
June 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28622577/hyperoside-inhibits-lipopolysaccharide-induced-inflammatory-responses-in-microglial-cells-via-p38-and-nf%C3%AE%C2%BAb-pathways
#12
Hui-Hui Fan, Lan-Bing Zhu, Ting Li, Hui Zhu, Ya-Nan Wang, Xiao-Li Ren, Bei-Lei Hu, Chen-Ping Huang, Jian-Hong Zhu, Xiong Zhang
Hyperoside (quercetin-3-O-β-d-galactoside) is an active compound isolated from herbs. Neuroinflammation is a key mechanism involved in neurodegenerative disorders including Parkinson's disease. In this study, we aimed to investigate the potentiality of hyperoside in inhibiting microglia-mediated neuroinflammation. BV2 microglial cells were pretreated with hyperoside and stimulated with lipopolysaccharide (LPS). The results showed that hyperoside significantly inhibited LPS-induced production of nitric oxide and pro-inflammatory cytokines including IL-1β and TNF-α, as well as the expression of inducible nitric oxide synthase...
June 13, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28622503/damed-in-trem-2-steps
#13
Sandro Da Mesquita, Jonathan Kipnis
The role of microglia in neurodegenerative diseases has been controversial. In this issue, Keren-Shaul et al. identify a unique population of disease-associated microglia (DAM) that develop in two steps and may help to restrict damage in Alzheimer and related diseases.
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28616718/effect-of-intrastriatal-6-ohda-lesions-on-extrastriatal-brain-structures-in-the-mouse
#14
Birte Becker, Melek Demirbas, Sonja Johann, Adib Zendedel, Cordian Beyer, Hans Clusmann, Stefan Jean-Pierre Haas, Andreas Wree, Sonny Kian Hwie Tan, Markus Kipp
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of midbrain dopaminergic neurons, resulting in motor and non-motor symptoms. The underlying pathology of non-motor symptoms is poorly understood. Discussed are pathological changes of extrastriatal brain structures. In this study, we characterized histopathological alterations of extrastriatal brain structures in the 6-hydroxydopamine (6-OHDA) PD animal model. Lesions were induced by unilateral stereotactic injections of 6-OHDA into the striatum or medial forebrain bundle of adult male mice...
June 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28612258/downregulated-glia-interplay-and-increased-mirna-155-as-promising-markers-to-track-als-at-an%C3%A2-early-stage
#15
Carolina Cunha, Catarina Santos, Cátia Gomes, Adelaide Fernandes, Alexandra Marçal Correia, Ana Maria Sebastião, Ana Rita Vaz, Dora Brites
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown cause. Absence of specific targets and biomarkers compromise the development of new therapeutic strategies and of innovative tools to stratify patients and assess their responses to treatment. Here, we investigate changes in neuroprotective-neuroinflammatory actions in the spinal cord of SOD1 (G93A) mice, at presymptomatic and symptomatic stages to identify stage-specific biomarkers and potential targets. Results showed that in the presymptomatic stage, there are alterations in both astrocytes and microglia, which comprise decreased expression of GFAP and S100B and upregulation of GLT-1, as well as reduced expression of CD11b, M2-phenotype markers, and a set of inflammatory mediators...
June 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28611577/the-anti-inflammatory-effects-of-lipoxygenase-and-cyclo-oxygenase-inhibitors-in-inflammation-induced-human-fetal-glia-cells-and-the-a%C3%AE-degradation-capacity-of-human-fetal-astrocytes-in-an-ex-vivo-assay
#16
Rea Pihlaja, Merja Haaparanta-Solin, Juha O Rinne
Chronic inflammation is a common phenomenon present in the background of multiple neurodegenerative diseases, including Alzheimer's disease (AD). The arachidonic acid pathway overproduces proinflammatory eicosanoids during these states and glial cells in the brain gradually lose their vital functions of protecting and supporting neurons. In this study, the role of different key enzymes of the eicosanoid pathway mediating inflammatory responses was examined in vitro and ex vivo using human fetal glial cells...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28602351/a-unique-microglia-type-associated-with-restricting-development-of-alzheimer-s-disease
#17
Hadas Keren-Shaul, Amit Spinrad, Assaf Weiner, Orit Matcovitch-Natan, Raz Dvir-Szternfeld, Tyler K Ulland, Eyal David, Kuti Baruch, David Lara-Astaiso, Beata Toth, Shalev Itzkovitz, Marco Colonna, Michal Schwartz, Ido Amit
Alzheimer's disease (AD) is a detrimental neurodegenerative disease with no effective treatments. Due to cellular heterogeneity, defining the roles of immune cell subsets in AD onset and progression has been challenging. Using transcriptional single-cell sorting, we comprehensively map all immune populations in wild-type and AD-transgenic (Tg-AD) mouse brains. We describe a novel microglia type associated with neurodegenerative diseases (DAM) and identify markers, spatial localization, and pathways associated with these cells...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28595911/manganese-exposure-exacerbates-progressive-motor-deficits-and-neurodegeneration-in-the-mitopark-mouse-model-of-parkinson-s-disease-relevance-to-gene-and-environment-interactions-in-metal-neurotoxicity
#18
Langley Monica R, Ghaisas Shivani, Ay Muhammet, Luo Jie, Palanisamy Bharathi N, Jin Huajun, Anantharam Vellareddy, Arthi Kanthasamy, Anumantha G Kanthasamy
Parkinson's disease (PD) is now recognized as a neurodegenerative condition caused by a complex interplay of genetic and environmental influences. Chronic manganese (Mn) exposure has been implicated in the development of PD. Since mitochondrial dysfunction is associated with PD pathology as well as Mn neurotoxicity, we investigated whether Mn exposure augments mitochondrial dysfunction and neurodegeneration in the nigrostriatal dopaminergic system using a newly available mitochondrially defective transgenic mouse model of PD, the MitoPark mouse...
June 5, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28595650/acute-neuroinflammation-induces-ais-structural-plasticity-in-a-nox2-dependent-manner
#19
S D Benusa, N M George, B A Sword, G H DeVries, J L Dupree
BACKGROUND: Chronic microglia-mediated inflammation and oxidative stress are well-characterized underlying factors in neurodegenerative disease, whereby reactive inflammatory microglia enhance ROS production and impact neuronal integrity. Recently, it has been shown that during chronic inflammation, neuronal integrity is compromised through targeted disruption of the axon initial segment (AIS), the axonal domain critical for action potential initiation. AIS disruption was associated with contact by reactive inflammatory microglia which wrap around the AIS, increasing association with disease progression...
June 8, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28595078/amyloidogenic-proteins-associated-with-neurodegenerative-diseases-activate-the-nlrp3-inflammasome
#20
REVIEW
Qian-Hang Shao, Xiao-Ling Zhang, Peng-Fei Yang, Yu-He Yuan, Nai-Hong Chen
Neuroinflammation has been shown as an essential factor in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, and Multiple Sclerosis. Furthermore, activated microglia and increased pro-inflammatory cytokines are the major hallmarks in neurodegenerative diseases. A multimolecular complex named as inflammasome is involved in the process of inflammatory response, which can activate inflammatory caspases, leading to the cleavage and secretion of inflammatory cytokines, and finally generates a potent inflammatory response...
June 5, 2017: International Immunopharmacology
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