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https://www.readbyqxmd.com/read/28937602/licochalcone-a-prevents-the-loss-of-dopaminergic-neurons-by-inhibiting-microglial-activation-in-lipopolysaccharide-lps-induced-parkinson-s-disease-models
#1
Bingxu Huang, Juxiong Liu, Chen Ju, Dongxue Yang, Guangxin Chen, Shiyao Xu, Yalong Zeng, Xuan Yan, Wei Wang, Dianfeng Liu, Shoupeng Fu
The neuroprotective effects of Licochalcone A (Lico.A), a flavonoid isolated from the herb licorice, in Parkinson's disease (PD) have not been elucidated. The prominent pathological feature of PD is the loss of dopaminergic neurons. The crucial role of neuroinflammation induced by activated microglia in dopaminergic neurodegeneration has been validated. In this study, we explore the therapeutic effects of Lico.A in lipopolysaccharide (LPS)-induced PD models in vivo and in vitro. We find that Lico.A significantly inhibits LPS-stimulated production of pro-inflammatory mediators and microglial activation by blocking the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and nuclear factor κB (NF-κB) p65 in BV-2 cells...
September 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28936789/toxic-synergism-between-quinolinic-acid-and-glutaric-acid-in-neuronal-cells-is-mediated-by-oxidative-stress-insights-to-a-new-toxic-model
#2
Paula Pierozan, Ana Laura Colín-González, Helena Biasibetti, Janaina Camacho da Silva, Angela Wyse, Moacir Wajner, Abel Santamaria
It has been shown that synergistic toxic effects of quinolinic acid (QUIN) and glutaric acid (GA), both in isolated nerve endings and in vivo conditions, suggest the contribution of these metabolites to neurodegeneration. However, this synergism still requires a detailed characterization of the mechanisms involved in cell damage during its occurrence. In this study, the effects of subtoxic concentrations of QUIN and/or GA were tested in neuronal cultures, co-cultures (neuronal cells + astrocytes), and mixed cultures (neuronal cells + astrocytes + microglia) from rat cortex and striatum...
September 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28924009/site-specific-regulation-of-p2x7-receptor-function-in-microglia-gates-morphine-analgesic-tolerance
#3
Heather Leduc-Pessah, Nicholas L Weilinger, Churmy Y Fan, Nicole E Burma, Roger J Thompson, Tuan Trang
Tolerance to the analgesic effects of opioids is a major problem in chronic pain management. Microglia are implicated in opioid tolerance, but the core mechanisms regulating their response to opioids remain obscure. By selectively ablating microglia in the spinal cord using a saporin-conjugated antibody to Mac1, we demonstrate a causal role for microglia in the development, but not maintenance, of morphine tolerance in male rats. Increased P2X7 receptor (P2X7R) activity is a cardinal feature of microglial activation, and in this study we found that morphine potentiates P2X7R-mediated Ca(2+) responses in resident spinal microglia acutely isolated from morphine tolerant rats...
September 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28923083/prevention-of-c5ar1-signaling-delays-microglial-inflammatory-polarization-favors-clearance-pathways-and-suppresses-cognitive-loss
#4
Michael X Hernandez, Shan Jiang, Tracy A Cole, Shu-Hui Chu, Maria I Fonseca, Melody J Fang, Lindsay A Hohsfield, Maria D Torres, Kim N Green, Rick A Wetsel, Ali Mortazavi, Andrea J Tenner
BACKGROUND: Pharmacologic inhibition of C5aR1, a receptor for the complement activation proinflammatory fragment, C5a, suppressed pathology and cognitive deficits in Alzheimer's disease (AD) mouse models. To validate that the effect of the antagonist was specifically via C5aR1 inhibition, mice lacking C5aR1 were generated and compared in behavior and pathology. In addition, since C5aR1 is primarily expressed on cells of the myeloid lineage, and only to a lesser extent on endothelial cells and neurons in brain, gene expression in microglia isolated from adult brain at multiple ages was compared across all genotypes...
September 18, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28912710/key-aging-associated-alterations-in-primary-microglia-response-to-beta-amyloid-stimulation
#5
Cláudia Caldeira, Carolina Cunha, Ana R Vaz, Ana S Falcão, Andreia Barateiro, Elsa Seixas, Adelaide Fernandes, Dora Brites
Alzheimer's disease (AD) is characterized by a progressive cognitive decline and believed to be driven by the self-aggregation of amyloid-β (Aβ) peptide into oligomers and fibrils that accumulate as senile plaques. It is widely accepted that microglia-mediated inflammation is a significant contributor to disease pathogenesis; however, different microglia phenotypes were identified along AD progression and excessive Aβ production was shown to dysregulate cell function. As so, the contribution of microglia to AD pathogenesis remains to be elucidated...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28911981/peripheral-immune-cells-infiltrate-into-sites-of-secondary-neurodegeneration-after-ischemic-stroke
#6
K A Jones, S Maltby, M W Plank, M Kluge, M Nilsson, P S Foster, F R Walker
Experimental stroke leads to microglia activation and progressive neuronal loss at sites of secondary neurodegeneration (SND). These lesions are remote from, but synaptically connected to, primary infarction sites. Previous studies have demonstrated that immune cells are present in sites of infarction in the first hours and days after stroke, and are associated with increased neurodegeneration in peri-infarct regions. However, it is not known whether immune cells are also present in more distal sites where SND occurs...
September 11, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28890869/multifunctional-biomimetic-spinal-cord-new-approach-to-repair-spinal-cord-injuries
#7
REVIEW
Yang Liu, Qian Li, Bin Zhang, De-Xiang Ban, Shi-Qing Feng
The incidence of spinal cord injury (SCI) has been gradually increasing, and the treatment has troubled the medical field all the time. Primary and secondary injuries ultimately lead to nerve impulse conduction block. Microglia and astrocytes excessively accumulate and proliferate to form the glial scar. At present, to reduce the effect of glial scar on nerve regeneration is a hot spot in the research on the treatment of SCI. According to the preliminary experiments, we would like to provide a new bionic spinal cord to reduce the negative effect of glial scar on nerve regeneration...
August 20, 2017: World Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28889993/a-subpopulation-of-activated-retinal-macrophages-selectively-migrated-to-regions-of-cone-photoreceptor-stress-but-had-limited-protective-effect-on-cone-death-in-a-mouse-model-for-type-2-leber-congenital-amaurosis
#8
Peter H Tang, Mark J Pierson, Neal D Heuss, Dale S Gregerson
BACKGROUND: Studies of antigen presentation in retina using mice that expressed green fluorescent protein (GFP) from a transgenic CD11c promoter found that retinal GFP(hi) cells possessed antigen presentation function. Subsequent studies found that these high GFP(hi) cells preferentially localized to sites of retinal injury, consistent with their APC function. Interest in the roles of macrophages in degenerative CNS diseases led us to study the GFP(hi) cells in a retinal model of neurodegeneration...
September 7, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28888963/sex-differences-in-the-mitochondrial-bioenergetics-of-astrocytes-but-not-microglia-at-a-physiologically-relevant-brain-oxygen-tension
#9
Sausan M Jaber, Evan A Bordt, Niraj M Bhatt, Daniel M Lewis, Sharon Gerecht, Gary Fiskum, Brian M Polster
Biological sex is thought to influence mitochondrial bioenergetic function. Previous respiration measurements examining brain mitochondrial sex differences were made at atmospheric oxygen using isolated brain mitochondria. Oxygen is 160 mm Hg (21%) in the atmosphere, while the oxygen tension in the brain generally ranges from ∼5 to 45 mm Hg (∼1-6% O2). This study tested the hypothesis that sex and/or brain physiological oxygen tension influence the mitochondrial bioenergetic properties of primary rat cortical astrocytes and microglia...
September 6, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28881033/the-conformational-epitope-for-a-new-a%C3%AE-42-protofibril-selective-antibody-partially-overlaps-with-the-peptide-n-terminal-region
#10
Benjamin A Colvin, Victoria A Rogers, Joshua A Kulas, Elizabeth A Ridgway, Fatima S Amtashar, Colin K Combs, Michael R Nichols
Aggregation and accumulation of amyloid-β peptide (Aβ) is a key component of Alzheimer's disease (AD). While monomeric Aβ appears to be benign, oligomers adopt a biologically detrimental structure. These soluble structures can be detected in AD brain tissue by antibodies that demonstrate selectivity for aggregated Aβ. Protofibrils are a subset of soluble oligomeric Aβ species and are described as small (<100 nm) curvilinear assemblies enriched in β-sheet structure. Our own in vitro studies demonstrate that microglial cells are much more sensitive to soluble Aβ42 protofibrils compared to Aβ42 monomer or insoluble Aβ42 fibrils...
September 7, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28843178/esculentoside-a-exerts-anti-inflammatory-activity-in-microglial-cells
#11
Hui Yang, Yijian Chen, Linjie Yu, Yun Xu
Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. This study was designed to evaluate the pharmacological effects of EsA on lipopolysaccharide (LPS)-stimulated BV2 microglia and primary microglia cells. Our results indicated that EsA pretreatment significantly decreased LPS-induced production of Nitric Oxide (NO) and Prostaglandin E2 (PGE2) and impeded LPS-mediated upregulation of pro-inflammatory mediators' expression such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-12 (IL-12) and tumor necrosis factor-a (TNF-α) in both BV2 microglia and primary microglia cells...
August 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28840509/kynurenic-acid-prevents-cytoskeletal-disorganization-induced-by-quinolinic-acid-in-mixed-cultures-of-rat-striatum
#12
Paula Pierozan, Helena Biasibetti-Brendler, Felipe Schmitz, Fernanda Ferreira, Regina Pessoa-Pureur, Angela T S Wyse
Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan known to modulate a number of mechanisms involved in neural dysfunction. Although its activity in the brain has been widely studied, the effect of KYNA counteracting the actions of quinolinic acid (QUIN) remains unknown. The present study aims at describing the ability of 100 μM KYNA preventing cytoskeletal disruption provoked by QUIN in astrocyte/neuron/microglia mixed culture. KYNA totally preserved cytoskeletal organization, cell morphology, and redox imbalance in mixed cultures exposed to QUIN...
August 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28836308/siglec-h-is-a-microglia-specific-marker-that-discriminates-microglia-from-cns-associated-macrophages-and-cns-infiltrating-monocytes
#13
Hiroyuki Konishi, Masaaki Kobayashi, Taikan Kunisawa, Kenta Imai, Akira Sayo, Bernard Malissen, Paul R Crocker, Katsuaki Sato, Hiroshi Kiyama
Several types of myeloid cell are resident in the CNS. In the steady state, microglia are present in the CNS parenchyma, whereas macrophages reside in boundary regions of the CNS, such as perivascular spaces, the meninges and choroid plexus. In addition, monocytes infiltrate into the CNS parenchyma from circulation upon blood-brain barrier breakdown after CNS injury and inflammation. Although several markers, such as CD11b and ionized calcium-binding adapter molecule 1 (Iba1), are frequently used as microglial markers, they are also expressed by other types of myeloid cell and microglia-specific markers were not defined until recently...
August 24, 2017: Glia
https://www.readbyqxmd.com/read/28836188/heme-oxygenase-1-inducing-activity-of-4-methoxydalbergione-and-4-hydroxy-4-methoxydalbergione-from-dalbergia-odorifera-and-their-anti-inflammatory-and-cytoprotective-effects-in-murine-hippocampal-and-bv2-microglial-cell-line-and-primary-rat-microglial-cells
#14
Dong-Cheol Kim, Dong-Sung Lee, Wonmin Ko, Kwan-Woo Kim, Hye Jin Kim, Chi-Su Yoon, Hyuncheol Oh, Youn-Chul Kim
Dalbergia odorifera T. Chen (Leguminosae) grows in Central and South America, Africa, Madagascar, and Southern Asia. D. odorifera possesses many useful pharmacological properties, such as antioxidative and anti-inflammatory activities in various cell types. 4-Methoxydalbergione (MTD) and 4'-hydroxy-4-methoxydalbergione (HMTD) were isolated from the EtOH extract of D. odorifera by several chromatography methods. The chemical structures were elucidated by nuclear magnetic resonance (NMR) and mass spectrum (MS)...
August 23, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28827545/molecular-diversity-and-potential-anti-neuroinflammatory-activities-of-cyathane-diterpenoids-from-the-basidiomycete-cyathus-africanus
#15
Jing Wei, Yuanyuan Cheng, Wan-Hui Guo, Da-Cheng Wang, Qiang Zhang, Ding Li, Jianhui Rong, Jin-Ming Gao
Ten new polyoxygenated cyathane diterpenoids, named neocyathins A-J (1-10), together with four known diterpenes (11-14), were isolated from the liquid culture of the medicinal basidiomycete fungus Cyathus africanus. The structures and configurations of these new compounds were elucidated through comprehensive spectroscopic analyses including 1D NMR, 2D NMR (HSQC, HMBC, NOESY) and HRESIMS, and electronic circular dichroism (ECD) data. Neuroinflammation is implicated in the pathogenesis of various neurodegenerative diseases, such as Alzheimers' disease (AD)...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807664/social-interaction-modulates-the-neuroinflammatory-response-to-global-cerebral-ischemia-in-male-mice
#16
Monica M Gaudier-Diaz, Ning Zhang, Adam H Haines, Surbhi, Min Zhou, A Courtney DeVries
Social isolation is a risk factor for cardiovascular and cerebrovascular diseases, although the underlying mechanisms remain underspecified. Considering the potential of microglia to become sensitized by stressors and their role in neuroinflammation, we hypothesized that social isolation primes microglia, resulting in an exaggerated neuroimmune response to experimental cerebral ischemia. First, major histocompatibility complex II (MHC II) gene expression, an indicator of microglial priming, was compared between mice that were socially isolated or pair-housed...
October 15, 2017: Brain Research
https://www.readbyqxmd.com/read/28797292/the-ethanol-extract-of-aquilariae-lignum-ameliorates-hippocampal-oxidative-stress-in-a-repeated-restraint-stress-mouse-model
#17
Hyun-Yong Lee, Jin-Seok Lee, Hyeong-Geug Kim, Won-Yong Kim, Seung-Bae Lee, Yung-Hyun Choi, Chang-Gue Son
BACKGROUND: Chronic stress contributes to the development of brain disorders, such as neurodegenerative and psychiatric diseases. Oxidative damage is well known as a causative factor for pathogenic process in brain tissues. The aim of this study is to evaluate the neuroprotective effect of a 30% ethanol extract of Aquilariae Lignum (ALE) in repeated stress-induced hippocampal oxidative injury. METHODS: Fifty BALB/c male mice (12 weeks old) were randomly divided into five groups (n = 10)...
August 10, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28782716/treatment-with-an-interleukin-1-receptor-antagonist-mitigates-neuroinflammation-and-brain-damage-after-polytrauma
#18
Mujun Sun, Rhys D Brady, David K Wright, Hyun Ah Kim, Shenpeng R Zhang, Christopher G Sobey, Maddison R Johnstone, Terence J O'Brien, Bridgette D Semple, Stuart J McDonald, Sandy R Shultz
Traumatic brain injury (TBI) and long bone fracture are common in polytrauma. This injury combination in mice results in elevated levels of the pro-inflammatory cytokine interleukin-1β (IL-1β) and exacerbated neuropathology when compared to isolated-TBI. Here we examined the effect of treatment with an IL-1 receptor antagonist (IL-1ra) in mice given a TBI and a concomitant tibial fracture (i.e., polytrauma). Adult male C57BL/6 mice were given sham-injuries or polytrauma and treated with saline-vehicle or IL-1ra (100 mg/kg)...
August 3, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28774571/activation-of-neonatal-microglia-can-be-influenced-by-other-neural-cells
#19
Alexandra Turano, Jennifer H Lawrence, Jaclyn M Schwarz
During development, microglial progenitor cells migrate into the brain from the periphery, a process critical to the maturation of the developing brain. Although they perform functions similar to mature, adult microglia, immature microglia are distinct from mature microglia. Activation of immature microglia, via an early-life immune challenge, can lead to persistent changes in microglial function, resulting in long-term neuronal and cognitive dysfunction. Early-life immune activation is associated with multiple neurodevelopmental disorders, including autism, ADHD, schizophrenia, and cerebral palsy - disorders with known or suspected immune etiologies, and strong sex biases for males...
September 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28772190/an-antigen-specific-semi-therapeutic-treatment-with-local-delivery-of-tolerogenic-factors-through-a-dual-sized-microparticle-system-blocks-experimental-autoimmune-encephalomyelitis
#20
Jonathan J Cho, Joshua M Stewart, Theodore T Drashansky, Maigan A Brusko, Ashley N Zuniga, Kyle J Lorentsen, Benjamin G Keselowsky, Dorina Avram
Antigen-specific treatments are highly desirable for autoimmune diseases in contrast to treatments which induce systemic immunosuppression. A novel antigen-specific therapy has been developed which, when administered semi-therapeutically, is highly efficacious in the treatment of the mouse model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). The treatment uses dual-sized, polymeric microparticles (dMPs) loaded with specific antigen and tolerizing factors for intra- and extra-cellular delivery, designed to recruit and modulate dendritic cells toward a tolerogenic phenotype without systemic release...
July 24, 2017: Biomaterials
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