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https://www.readbyqxmd.com/read/28453542/phospholipid-profiling-of-plasma-from-gw-veterans-and-rodent-models-to-identify-potential-biomarkers-of-gulf-war-illness
#1
Tanja Emmerich, Zuchra Zakirova, Nancy Klimas, Kimberly Sullivan, Ashok K Shetty, James E Evans, Ghania Ait-Ghezala, Gary S Laco, Bharathi Hattiangady, Geetha A Shetty, Michael Mullan, Gogce Crynen, Laila Abdullah, Fiona Crawford
Gulf War Illness (GWI), which affects at least one fourth of the 700,000 veterans deployed to the Gulf War (GW), is characterized by persistent and heterogeneous symptoms, including pain, fatigue and cognitive problems. As a consequence, this illness remains difficult to diagnose. Rodent models have been shown to exhibit different symptomatic features of GWI following exposure to particular GW agents (e.g. pyridostigmine bromide, permethrin and DEET) and/or stress. Preclinical analyses have shown the activation of microglia and astroglia as a pathological hallmark in these mouse and rat models...
2017: PloS One
https://www.readbyqxmd.com/read/28445772/rosiglitazone-pretreatment-influences-thrombin-induced-phagocytosis-by-rat-microglia-via-activating-ppar%C3%AE-and-cd36
#2
Qiong Mu, Likun Wang, Hang Hang, Chunfeng Liu, Guofeng Wu
OBJECTIVE: To explore the protective role of rosiglitazone against secondary brain injury after cerebral hemorrhage, we investigated the effect of rosiglitazone pretreatment on thrombin-induced microglial phagocytosis and described the molecular mechanisms involved in this process. METHODS: Primary microglial cells were obtained from the brain tissue of newborn Sprague-Dawley rats and were randomly divided into four groups: the normal, thrombin stimulation, thrombin-treated plus rosiglitazone, and thrombin-rosiglitazone plus proliferator-activated receptor-gamma (PPARγ) antagonist groups...
April 23, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28445478/delayed-histochemical-alterations-within-the-neurovascular-unit-due-to-transient-focal-cerebral-ischemia-and-experimental-treatment-with-neurotrophic-factors
#3
Dominik Michalski, Roman Pitsch, Deepu R Pillai, Bianca Mages, Susanne Aleithe, Jens Grosche, Henrik Martens, Felix Schlachetzki, Wolfgang Härtig
Current stroke therapy is focused on recanalizing strategies, but neuroprotective co-treatments are still lacking. Modern concepts of the ischemia-affected neurovascular unit (NVU) and surrounding penumbra emphasize the complexity during the transition from initial damaging to regenerative processes. While early treatment with neurotrophic factors was shown to result in lesion size reduction and blood-brain barrier (BBB) stabilization, cellular consequences from these treatments are poorly understood. This study explored delayed cellular responses not only to ischemic stroke, but also to an early treatment with neurotrophic factors...
2017: PloS One
https://www.readbyqxmd.com/read/28442752/zika-virus-infection-reprograms-global-transcription-of-host-cells-to-allow-sustained-infection
#4
Shashi Kant Tiwari, Jason Dang, Yue Qin, Gianluigi Lichinchi, Vikas Bansal, Tariq M Rana
Zika virus (ZIKV) is an emerging virus causally linked to neurological disorders, including congenital microcephaly and Guillain-Barré syndrome. There are currently no targeted therapies for ZIKV infection. To identify novel antiviral targets and to elucidate the mechanisms by which ZIKV exploits the host cell machinery to support sustained replication, we analyzed the transcriptomic landscape of human microglia, fibroblast, embryonic kidney and monocyte-derived macrophage cell lines before and after ZIKV infection...
April 26, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28442549/neuraminidases-3-and-4-regulate-neuronal-function-by-catabolizing-brain-gangliosides
#5
Xuefang Pan, Camila De Britto Pará De Aragão, Juan P Velasco-Martin, David A Priestman, Harry Y Wu, Kohta Takahashi, Kazunori Yamaguchi, Luisella Sturiale, Domenico Garozzo, Frances M Platt, Nathalie Lamarche-Vane, Carlos R Morales, Taeko Miyagi, Alexey V Pshezhetsky
Gangliosides (sialylated glycolipids) play an essential role in the CNS by regulating recognition and signaling in neurons. Metabolic blocks in processing and catabolism of gangliosides result in the development of severe neurologic disorders, including gangliosidoses manifesting with neurodegeneration and neuroinflammation. We demonstrate that 2 mammalian enzymes, neuraminidases 3 and 4, play important roles in catabolic processing of brain gangliosides by cleaving terminal sialic acid residues in their glycan chains...
April 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28441118/mechanisms-of-hippocampal-aging-and-the-potential-for-rejuvenation
#6
Xuelai Fan, Elizabeth G Wheatley, Saul A Villeda
The past two decades have seen remarkable progress in our understanding of the multifactorial drivers of hippocampal aging and cognitive decline. Recent findings have also raised the possibility of functional rejuvenation in the aged hippocampus. In this review, we aim to synthesize the mechanisms that drive hippocampal aging and evaluate critically the potential for rejuvenation. We discuss the functional changes in synaptic plasticity and regenerative potential of the aged hippocampus, followed by mechanisms of microglia aging, and assess the cross talk between these proaging processes...
April 24, 2017: Annual Review of Neuroscience
https://www.readbyqxmd.com/read/28434692/immune-hyperreactivity-of-a%C3%AE-plaque-associated-microglia-in-alzheimer-s-disease
#7
Zhuoran Yin, Divya Raj, Nasrin Saiepour, Debby Van Dam, Nieske Brouwer, Inge R Holtman, Bart J L Eggen, Thomas Möller, Joseph A Tamm, Aicha Abdourahman, Elly M Hol, Willem Kamphuis, Thomas A Bayer, Peter P De Deyn, Erik Boddeke
Alzheimer's disease (AD) is strongly associated with microglia-induced neuroinflammation. Particularly, Aβ plaque-associated microglia take on an "activated" morphology. However, the function and phenotype of these Aβ plaque-associated microglia are not well understood. We show hyperreactivity of Aβ plaque-associated microglia upon systemic inflammation in transgenic AD mouse models (i.e., 5XFAD and APP23). Gene expression profiling of Aβ plaque-associated microglia (major histocompatibility complex II(+) microglia) isolated from 5XFAD mice revealed a proinflammatory phenotype...
March 27, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28434164/microglia-loss-contributes-to-the-development-of-major-depression-induced-by-different-types-of-chronic-stresses
#8
Lijuan Tong, Yu Gong, Peng Wang, Wenfeng Hu, Jili Wang, Zhuo Chen, Wei Zhang, Chao Huang
Recently, the loss and dystrophy of hippocampal microglia induced by chronic unpredictable stress (CUS) has been reported to mediate the development of major depression in mice whose microglial cells were labeled with enhanced green fluorescent protein-conjuncted-CX3C receptor type 1. However, whether this happens in endogenous microglia with no genetic intervention remains unclear. Here, we addressed this issue in mice treated with different types of chronic stresses, including the CUS, chronic restraint stress (CRS) and chronic social defeat stress (CSDS)...
April 22, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28432601/neuropathic-pain-central-vs-peripheral-mechanisms
#9
REVIEW
Kathleen Meacham, Andrew Shepherd, Durga P Mohapatra, Simon Haroutounian
PURPOSE OF REVIEW: Our goal is to examine the processes-both central and peripheral-that underlie the development of peripherally-induced neuropathic pain (pNP) and to highlight recent evidence for mechanisms contributing to its maintenance. While many pNP conditions are initiated by damage to the peripheral nervous system (PNS), their persistence appears to rely on maladaptive processes within the central nervous system (CNS). The potential existence of an autonomous pain-generating mechanism in the CNS creates significant implications for the development of new neuropathic pain treatments; thus, work towards its resolution is crucial...
June 2017: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/28427563/neuroinflammation-in-alzheimer-s-disease-the-preventive-and-therapeutic-potential-of-polyphenolic-nutraceuticals
#10
Yousef Sawikr, Nagendra Sastry Yarla, Ilaria Peluso, Mohammad Amjad Kamal, Gjumrakch Aliev, Anupam Bishayee
Brain inflammation, characterized by increased microglia and astrocyte activation, increases during aging and is a key feature of neurodegenerative diseases, such as Alzheimer's disease (AD). In AD, neuronal death and synaptic impairment, induced by amyloid-β (Aβ) peptide, are at least in part mediated by microglia and astrocyte activation. Glial activation results in the sustained production of proinflammatory cytokines and reactive oxygen species, giving rise to a chronic inflammatory process. Astrocytes are the most abundant glial cells in the central nervous system and are involved in the neuroinflammation...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28427446/respiratory-chain-complex-iii-deficiency-due-to-mutated-bcs1l-a-novel-phenotype-with-encephalomyopathy-partially-phenocopied-in-a-bcs1l-mutant-mouse-model
#11
Saara Tegelberg, Nikica Tomašić, Jukka Kallijärvi, Janne Purhonen, Eskil Elmér, Eva Lindberg, David Gisselsson Nord, Maria Soller, Nicole Lesko, Anna Wedell, Helene Bruhn, Christoph Freyer, Henrik Stranneheim, Rolf Wibom, Inger Nennesmo, Anna Wredenberg, Erik A Eklund, Vineta Fellman
BACKGROUND: Mitochondrial diseases due to defective respiratory chain complex III (CIII) are relatively uncommon. The assembly of the eleven-subunit CIII is completed by the insertion of the Rieske iron-sulfur protein, a process for which BCS1L protein is indispensable. Mutations in the BCS1L gene constitute the most common diagnosed cause of CIII deficiency, and the phenotypic spectrum arising from mutations in this gene is wide. RESULTS: A case of CIII deficiency was investigated in depth to assess respiratory chain function and assembly, and brain, skeletal muscle and liver histology...
April 20, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28422748/therapeutic-inhibition-of-soluble-brain-tnf-promotes-remyelination-by-increasing-myelin-phagocytosis-by-microglia
#12
Maria Karamita, Christopher Barnum, Wiebke Möbius, Malú G Tansey, David E Szymkowski, Hans Lassmann, Lesley Probert
Multiple sclerosis (MS) is an inflammatory CNS demyelinating disease in which remyelination largely fails. Transmembrane TNF (tmTNF) and TNF receptor 2 are important for remyelination in experimental MS models, but it is unknown whether soluble TNF (solTNF), a major proinflammatory factor, is involved in regeneration processes. Here, we investigated the specific contribution of solTNF to demyelination and remyelination in the cuprizone model. Treatment with XPro1595, a selective inhibitor of solTNF that crosses the intact blood-brain barrier (BBB), in cuprizone-fed mice did not prevent toxin-induced oligodendrocyte loss and demyelination, but it permitted profound early remyelination due to improved phagocytosis of myelin debris by CNS macrophages and prevented disease-associated decline in motor performance...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28417261/neutrophil-infiltration-and-matrix-metalloproteinase-9-in-lacunar-infarction
#13
Wolfgang Walz, Francisco S Cayabyab
We use the modified pial vessel disruption rat model to elucidate the cellular and molecular mechanisms of cavitation as it plays a role in lacunar infarction. Here we discuss the similarities between the genesis of pulmonary cavitation in various animal models and lacunar infarction in the cerebral cortex of rats. Both pathological processes involve the creation of a cavity surrounded by fibroblasts or reactive astrocytes. A crucial step in both, the lung and the cerebral cortex, appears to be the migration of neutrophils across the endothelial barrier into the parenchyma...
April 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28414331/a-new-fate-mapping-system-reveals-context-dependent-random-or-clonal-expansion-of-microglia
#14
Tuan Leng Tay, Dominic Mai, Jana Dautzenberg, Francisco Fernández-Klett, Gen Lin, Sagar, Moumita Datta, Anne Drougard, Thomas Stempfl, Alberto Ardura-Fabregat, Ori Staszewski, Anca Margineanu, Anje Sporbert, Lars M Steinmetz, J Andrew Pospisilik, Steffen Jung, Josef Priller, Dominic Grün, Olaf Ronneberger, Marco Prinz
Microglia constitute a highly specialized network of tissue-resident immune cells that is important for the control of tissue homeostasis and the resolution of diseases of the CNS. Little is known about how their spatial distribution is established and maintained in vivo. Here we establish a new multicolor fluorescence fate mapping system to monitor microglial dynamics during steady state and disease. Our findings suggest that microglia establish a dense network with regional differences, and the high regional turnover rates found challenge the universal concept of microglial longevity...
April 17, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28410147/the-roles-of-microglia-macrophages-in-tumor-progression-of-brain-cancer-and-metastatic-disease
#15
Shih-Ying Wu, Kounosuke Watabe
Malignant brain tumors and brain metastases are highly aggressive diseases that are often resistant to treatment. Consequently, the current prognosis of patients with brain tumors and metastases is dismal. Activated microglia and macrophages are often observed in close proximity to or within the malignant tumor masses, suggesting that microglia/macrophages play an important role in brain tumor progression. Microglia, being resident macrophages of the central nervous system, form a major component of the brain immune system...
June 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28409994/a-novel-porcine-ex-vivo-retina-culture-model-for-oxidative-stress-induced-by-h%C3%A2-o%C3%A2
#16
José Hurst, Sandra Kuehn, Adelina Jashari, Teresa Tsai, Karl Ulrich Bartz-Schmidt, Sven Schnichels, Stephanie C Joachim
Oxidative stress is a key player in many ophthalmic diseases. However, the role of oxidative stress in most degenerative processes is not yet known. Therefore, accurate and practical models are required to efficiently screen for therapeutics. Porcine eyes are closely related to the human eye, and can be obtained from the abattoir as a by-product of the food industry. Therefore, they offer excellent opportunities for the development of culture models with which to pre-screen potential therapies, while reducing the use of laboratory animals...
March 2017: Alternatives to Laboratory Animals: ATLA
https://www.readbyqxmd.com/read/28407740/mu-opioid-receptor-and-delta-opioid-receptor-differentially-regulate-microglial-inflammatory-response-to-control-proopiomelanocortin-neuronal-apoptosis-in-the-hypothalamus-effects-of-neonatal-alcohol
#17
Pallavi Shrivastava, Miguel A Cabrera, Lucy G Chastain, Nadka I Boyadjieva, Shaima Jabbar, Tina Franklin, Dipak K Sarkar
BACKGROUND: Opioid receptors are known to control neurotransmission of various peptidergic neurons, but their potential role in regulation of microglia and neuronal cell communications is unknown. We investigated the role of mu-opioid receptors (MOR) and delta-opioid receptors (DOR) on microglia in the regulation of apoptosis in proopiomelanocortin (POMC) neurons induced by neonatal ethanol in the hypothalamus. METHODS: Neonatal rat pups were fed a milk formula containing ethanol or control diets between postnatal days 2-6...
April 14, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28407242/the-role-of-autophagy-in-pro-inflammatory-responses-of-microglia-activation-via-mitochondrial-reactive-oxygen-species-in-vitro
#18
Junli Ye, Zhongxin Jiang, Xuehong Chen, Mengyang Liu, Jing Li, Na Liu
Microglia over-activation contributes to neurodegenerative processes by neurotoxin factors and pro-inflammatory molecules of pro-inflammatory processes. Mitochondrial reactive oxygen species (ROS) and autophagy pathway might be involved in microglial activation, but the underlying mechanism is unclear. Here we regulated autophagy pathway of microglia in vitro by autophagy inhibition (3-methyladenine treatment, siRNA-Beclin 1 or siRNA-ATG5 transfection) or induction (rapamycin treatment) in murine microglial BV-2 cells or cultured primary mouse microglial cells...
April 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28395090/immune-cell-infiltrates-in-hippocampal-sclerosis-correlation-with-neuronal-loss
#19
Jian-Qiang Lu, Trevor A Steve, Matt Wheatley, Donald W Gross
Immune mechanisms have been increasingly recognized in the pathogenesis of hippocampal sclerosis (HS), but infiltration of cytotoxic T-cells and its pathological significance in patients with HS has not been explored. We examined 30 cases of surgically resected hippocampi, including 16 International League Against Epilepsy (ILAE) type 1, 9 ILAE type 2, 1 ILAE type 3 HS, and 4 ILAE No-HS, as well as 6 autopsy No-HS hippocampi. The HS hippocampi showed sparse to scattered CD8-positive T-cells, rare CD4-positive T-cells, and a modest increase in CD68-positive microglia/macrophages, which were significantly more numerous than those in the No-HS controls...
March 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28388927/exposure-to-gestational-diabetes-mellitus-induces-neuroinflammation-derangement-of-hippocampal-neurons-and-cognitive-changes-in-rat-offspring
#20
Billy Vuong, Gary Odero, Stephanie Rozbacher, Mackenzie Stevenson, Stephanie M Kereliuk, Troy J Pereira, Vernon W Dolinsky, Tiina M Kauppinen
BACKGROUND: Birth cohort studies link gestational diabetes mellitus (GDM) with impaired cognitive performance in the offspring. However, the mechanisms involved are unknown. We tested the hypothesis that obesity-associated GDM induces chronic neuroinflammation and disturbs the development of neuronal circuitry resulting in impaired cognitive abilities in the offspring. METHODS: In rats, GDM was induced by feeding dams a diet high in sucrose and fatty acids. Brains of neonatal (E20) and young adult (15-week-old) offspring of GDM and lean dams were analyzed by immunohistochemistry, cytokine assay, and western blotting...
April 7, 2017: Journal of Neuroinflammation
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