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https://www.readbyqxmd.com/read/28533741/adulthood-exposure-to-lipopolysaccharide-exacerbates-the-neurotoxic-and-inflammatory-effects-of-rotenone-in-the-substantia-nigra
#1
Chun Huang, Li Zhu, Huan Li, Fu-Guo Shi, Guo-Qing Wang, Yi-Zheng Wei, Jie Liu, Feng Zhang
Parkinson's disease (PD) is the second most neurodegenerative disorder with a regional decrease of dopamine (DA) neurons in the substantia nigra (SN). Despite intense exploration, the etiology of PD progressive process remains unclear. This study was to investigate the synergistic effects of systemic inflammation of lipopolysaccharide (LPS) and neurotoxicity of rotenone (ROT) on exacerbating DA neuron lesion. Male SD adulthood rats received a single intraperitoneal injection of LPS. Seven months later, rats were subcutaneously given ROT five times a week for consecutive 4 weeks...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28528700/directed-differentiation-of-human-pluripotent-stem-cells-to-microglia
#2
Panagiotis Douvaras, Bruce Sun, Minghui Wang, Ilya Kruglikov, Gregory Lallos, Matthew Zimmer, Cecile Terrenoire, Bin Zhang, Sam Gandy, Eric Schadt, Donald O Freytes, Scott Noggle, Valentina Fossati
Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microglia from pluripotent stem cells. Myeloid progenitors expressing CD14/CX3CR1 were generated within 30 days of differentiation from both embryonic and induced pluripotent stem cells (iPSCs). Further differentiation of the progenitors resulted in ramified microglia with highly motile processes, expressing typical microglial markers...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28526328/acrylamide-induced-neurotoxicity-in-primary-astrocytes-and-microglia-roles-of-the-nrf2-are-and-nf-%C3%AE%C2%BAb-pathways
#3
Mengyao Zhao, Fu Sheng Lewis Wang, Xiaosong Hu, Fang Chen, Hing Man Chan
Acrylamide (AA) is a common food contaminant formed during food heat processing that has neurotoxic effects. We hypothesize that AA induces oxidative stress in astrocytes and microglia, leading to neurotoxicity. Oxidative status, translocation of Nrf2 and NF-κB, and related down-stream targets were measured in primary astrocytes and microglia obtained from BALB/c mice. The results showed that AA increased reactive oxygen species (ROS) formation and reduced glutathione levels, causing successive events associated with oxidative stress, including 4-hydroxynonenal and 8-hydroxy-2-deoxyguanosine adduct formation, in both cell types...
May 16, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28522962/alterations-in-cd200-cd200r1-system-during-eae-already-manifest-at-presymptomatic-stages
#4
Tony Valente, Joan Serratosa, Unai Perpiñá, Josep Saura, Carme Solà
In the brain of patients with multiple sclerosis, activated microglia/macrophages appear in active lesions and in normal appearing white matter. However, whether they play a beneficial or a detrimental role in the development of the pathology remains a controversial issue. The production of pro-inflammatory molecules by chronically activated microglial cells is suggested to contribute to the progression of neurodegenerative processes in neurological disease. In the healthy brain, neurons control glial activation through several inhibitory mechanisms, such as the CD200-CD200R1 interaction...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28522413/microglia-support-atf3-positive-neurons-following-hypoglossal-nerve-axotomy
#5
Tatsuhide Tanaka, Koichi Murakami, Yoshio Bando, Taichi Nomura, Ayami Isonishi, Shoko Morita-Takemura, Kouko Tatsumi, Akio Wanaka, Shigetaka Yoshida
Microglia are essential in developmental processes and maintenance of neuronal homeostasis. Experimental axotomy of motor neurons results in neurodegeneration, and microglia in motor nuclei become activated and migrate towards injured neurons. However, whether these activated microglia are protective or destructive to neurons remains controversial. In the present study, we transected the hypoglossal nerve in BALB/c mice, causing activating transcription factor 3 (ATF3) and growth associated protein 43 (GAP43) induction, and partial neuronal death...
May 15, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28516240/in-vivo-pet-imaging-of-neuroinflammation-in-alzheimer-s-disease
#6
REVIEW
Julien Lagarde, Marie Sarazin, Michel Bottlaender
Increasing evidence suggests that neuroinflammation contributes to the pathophysiology of many neurodegenerative diseases, especially Alzheimer's disease (AD). Molecular imaging by PET may be a useful tool to assess neuroinflammation in vivo, thus helping to decipher the complex role of inflammatory processes in the pathophysiology of neurodegenerative diseases and providing a potential means of monitoring the effect of new therapeutic approaches. For this objective, the main target of PET studies is the 18 kDa translocator protein (TSPO), as it is overexpressed by activated microglia...
May 17, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28515492/the-brain-sirtuins-and-ageing
#7
REVIEW
Akiko Satoh, Shin-Ichiro Imai, Leonard Guarente
In mammals, recent studies have demonstrated that the brain, the hypothalamus in particular, is a key bidirectional integrator of humoral and neural information from peripheral tissues, thus influencing ageing both in the brain and at the 'systemic' level. CNS decline drives the progressive impairment of cognitive, social and physical abilities, and the mechanisms underlying CNS regulation of the ageing process, such as microglia-neuron networks and the activities of sirtuins, a class of NAD(+)-dependent deacylases, are beginning to be understood...
May 18, 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/28508369/spike-in-silac-approach-for-proteomic-analysis-of-ex-vivo-microglia
#8
Joao Paulo Costa Pinho, Harris Bell-Temin, Bin Liu, Stanley M Stevens
Stable isotope labeling by amino acids in cell culture (SILAC) is a versatile mass spectrometry-based proteomic approach that can achieve accurate relative protein quantitation on a global scale. In this approach, proteins are labeled while being synthesized by the cell due to the presence of certain amino acids exclusively as heavier mass analogs than their regular (light) counterparts. This differential labeling allows for the identification of heavy and light forms of each peptide corresponding to two or more different experimental groups upon mass spectrometric analysis, the intensities of which reflect their abundance in the sample analyzed...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28508368/de-novo-and-uninterrupted-silac-labeling-of-primary-microglia
#9
Ping Zhang, Ashley Culver-Cochran, Stanley M Stevens, Bin Liu
Microglia have increasingly been recognized as playing a wide spectrum of roles in various physiological and pathological processes in the central nervous system. Studies in the past have mostly associated individual microglial enzymes or soluble factors such as cytokines with specific functions of microglia. Stable isotope labeling with amino acids in cell culture (SILAC)-based proteomic analysis enables an unbiased, simultaneous, and global-scale analysis of the expression of thousands of proteins involved in key cellular pathways that regulate microglial activities...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28501776/inhibition-of-senp3-by-urb597-ameliorates-neurovascular-unit-dysfunction-in-rats-with-chronic-cerebral-hypoperfusion
#10
Da-Peng Wang, Ke-Jia Liu, Graham Kasper, Qi Lin, Jian Hai
Disruption of the neurovascular unit (NVU), induced by chronic cerebral hypoperfusion (CCH), has been broadly found in various neurological disorders. SUMO-specific protease 3 (SENP3) is expressed in neurons, astrocytes, and microglia, and regulates a variety of cell events. However, whether SENP3 is involved in neurovascular injury under the condition of CCH is still elusive. To address this issue, we investigated the effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on NVU and the role of SENP3 in this process, as well as the underling mechanisms...
May 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28499503/mast-cells-in-neuroinflammation-and-brain-disorders
#11
REVIEW
Erik Hendriksen, Doris van Bergeijk, Ronald S Oosting, Frank A Redegeld
It is well recognized that neuroinflammation is involved in the pathogenesis of various neurodegenerative diseases. Microglia and astrocytes are major pathogenic components within this process and known to respond to proinflammatory mediators released from immune cells such as mast cells. Mast cells reside in the brain and are an important source of inflammatory molecules. Mast cell interactions with glial cells and neurons result in the release of mediators such as cytokines, proteases and reactive oxygen species...
May 10, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28495611/hiv-1-tat-protein-enhances-sensitization-to-methamphetamine-by-affecting-dopaminergic-function
#12
James P Kesby, Julia A Najera, Benedetto Romoli, Yiding Fang, Liana Basova, Amanda Birmingham, Maria Cecilia G Marcondes, Davide Dulcis, Svetlana Semenova
Methamphetamine abuse is common among humans with immunodeficiency virus (HIV). The HIV-1 regulatory protein TAT induces dysfunction of mesolimbic dopaminergic systems which may result in impaired reward processes and contribute to methamphetamine abuse. These studies investigated the impact of TAT expression on methamphetamine-induced locomotor sensitization, underlying changes in dopamine function and adenosine receptors in mesolimbic brain areas and neuroinflammation (microgliosis). Transgenic mice with doxycycline-induced TAT protein expression in the brain were tested for locomotor activity in response to repeated methamphetamine injections and methamphetamine challenge after a 7-day abstinence period...
May 8, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28495374/metyrapone-prevents-brain-damage-induced-by-status-epilepticus-in-the-rat-lithium-pilocarpine-model
#13
Luis García-García, Ahmed A Shiha, Rubén Fernández de la Rosa, Mercedes Delgado, Ágata Silván, Pablo Bascuñana, Jens P Bankstahl, Francisca Gomez, Miguel A Pozo
The status epilepticus (SE) induced by lithium-pilocarpine is a well characterized rodent model of the human temporal lobe epilepsy (TLE) which is accompanied by severe brain damage. Stress and glucocorticoids markedly contribute to exacerbate neuronal damage induced by seizures but the underlying mechanisms are poorly understood. Herein we sought to investigate whether a single administration of metyrapone (150 mg/kg, i.p.), an 11β-hydroxylase inhibitor, enzyme involved in the peripheral and central synthesis of corticosteroids, had neuroprotective properties in this model...
May 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28495139/high-yield-primary-microglial-cultures-using-granulocyte-macrophage-colony-stimulating-factor-from-embryonic-murine-cerebral-cortical-tissue
#14
Adam C Yu, Sarah E Neil, Jacqueline A Quandt
BACKGROUND: Microglia play vital roles in neurotrophic support and modulating immune or inflammatory responses to pathogens or damage/stressors during disease. This study describes the ability to establish large numbers of microglia from embryonic tissues with the addition of granulocyte-macrophage stimulating factor (GM-CSF) and characterizes their similarities to adult microglia examined ex vivo as well as their responses to inflammatory mediators. METHOD: Microglia were seeded from a primary embryonic mixed cortical suspension with the addition of GM-CSF...
June 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28490373/thioredoxin-interacting-protein-links-endoplasmic-reticulum-stress-to-inflammatory-brain-injury-and-apoptosis-after-subarachnoid-haemorrhage
#15
Qing Zhao, Xudong Che, Hongxia Zhang, Pianpian Fan, Guanping Tan, Liu Liu, Dengzhi Jiang, Jun Zhao, Xiang Xiang, Yidan Liang, Xiaochuan Sun, Zhaohui He
BACKGROUND: Early brain injury (EBI) is considered a major contributor to the high morbidity and mortality associated with subarachnoid haemorrhage (SAH). Both of sterile inflammation and apoptosis are considered the important causes of EBI. Recently, it was confirmed that thioredoxin-interacting protein (TXNIP) not only participates in inflammatory amplification but also stimulates the apoptosis signalling cascade pathway. However, whether the effects of TXNIP influence the pathogenesis of SAH remains unclear...
May 11, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28487629/exosomes-as-carriers-of-alzheimer-s-amyloid-%C3%A3
#16
REVIEW
Kohei Yuyama, Yasuyuki Igarashi
The intracerebral level of the aggregation-prone peptide, amyloid-ß (Aß), is constantly maintained by multiple clearance mechanisms, including several degradation enzymes, and brain efflux. Disruption of the clearance machinery and the resultant Aß accumulation gives rise to neurotoxic assemblies, leading to the pathogenesis of Alzheimer's disease (AD). In addition to the classic mechanisms of Aß clearance, the protein may be processed by secreted vesicles, although this possibility has not been extensively investigated...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28486969/activation-of-p2x7-receptor-and-nlrp3-inflammasome-assembly-in-hippocampal-glial-cells-mediates-chronic-stress-induced-depressive-like-behaviors
#17
Na Yue, Huijie Huang, Xiaocang Zhu, Qiuqin Han, Yalin Wang, Bing Li, Qiong Liu, Gencheng Wu, Yuqiu Zhang, Jin Yu
BACKGROUND: In recent years, proinflammatory cytokine interleukin-1β (IL-1β) was considered to play a critical role in the pathogenesis of depression. In addition, P2X7 receptor (P2X7R), a member of the purinergic receptor family, which is predominantly present on microglia, as well as on astrocytes and neurons in lesser amounts in the central nervous system, was suggested to be involved in the processing and releasing of IL-1β. Here, we investigated the role of P2X7R in the pathogenesis of depression...
May 10, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28483841/trem2-deficiency-impairs-chemotaxis-and-microglial-responses-to-neuronal-injury
#18
Fargol Mazaheri, Nicolas Snaidero, Gernot Kleinberger, Charlotte Madore, Anna Daria, Georg Werner, Susanne Krasemann, Anja Capell, Dietrich Trümbach, Wolfgang Wurst, Bettina Brunner, Sebastian Bultmann, Sabina Tahirovic, Martin Kerschensteiner, Thomas Misgeld, Oleg Butovsky, Christian Haass
Sequence variations in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to an increased risk for neurodegenerative disorders such as Alzheimer's disease and frontotemporal lobar degeneration. In the brain, TREM2 is predominantly expressed in microglia. Several disease-associated TREM2 variants result in a loss of function by reducing microglial phagocytosis, impairing lipid sensing, preventing binding of lipoproteins and affecting shielding of amyloid plaques. We here investigate the consequences of TREM2 loss of function on the microglia transcriptome...
May 8, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28480882/dysfunction-of-microglial-stat3-alleviates-depressive-behavior-via-neuron-microglia-interactions
#19
Sun-Ho Kwon, Jeong-Kyu Han, Moonseok Choi, Yong-Jin Kwon, Sung Joon Kim, Eun Hee Yi, Jae-Cheon Shin, Ik-Hyun Cho, Byung-Hak Kim, Sang Jeong Kim, Sang-Kyu Ye
Neuron-microglia interactions play a crucial role in maintaining the neuroimmune system. The balance of neuroimmune system has emerged as an important process in the pathophysiology of depression. However, how neuron-microglia interactions contribute to major depressive disorders has been poorly understood. Herein, we demonstrated that microglia-derived synaptic changes induced antidepressive-like behavior by using microglia-specific signal transducer and activator of transcription 3 (STAT3) knockout (STAT3(fl/fl);LysM-Cre(+/-)) mice...
May 8, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28478826/novel-aspects-of-defensins-involvement-in-virus-induced-autoimmunity-in-the-central-nervous-system
#20
Evangelos I Kazakos, Jannis Kountouras, Stergios A Polyzos, Georgia Deretzi
Recent research on re-circulation of interstitial fluid from the brain parenchyma to the periphery and its inferred importance in immune surveillance dysregulation are changing our conceptualization of the pathophysiology of virus-induced autoimmunity. In this context, it is necessary to reassess the immunomodulatory properties of human defensins that are variably expressed by cerebral microglia, astrocytes and choroid plexus epithelial cells and exhibit complex and often confounding roles in neuroinflammatory processes...
May 2017: Medical Hypotheses
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