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https://www.readbyqxmd.com/read/29454265/supplementation-of-lycopene-attenuates-lipopolysaccharide-induced-amyloidogenesis-and-cognitive-impairments-via-mediating-neuroinflammation-and-oxidative-stress
#1
Jia Wang, Lixia Li, Zhuo Wang, Yifan Cui, Xintong Tan, Tian Yuan, Qian Liu, Zhigang Liu, Xuebo Liu
Neuroinflammation is documented to be the major culprit of Alzheimer's disease. Lycopene (LYC), a fat soluble carotenoid, exhibits neuroprotective function in several neurodegenerative disorders. However, the effects of LYC to countering systemic inflammation-induced amyloidogenesis and memory deficiency remain to be elucidated. In current study, 3-month-old male C57BL/6J mice were treated with 0.03% LYC (w/w, mixed into normal chow) for 5 weeks. The mice were then treated by intraperitoneal injection of LPS (0...
February 2, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29449568/binge-alcohol-exposure-causes-neurobehavioral-deficits-and-gsk3%C3%AE-activation-in-the-hippocampus-of-adolescent-rats
#2
Zhe Ji, Lin Yuan, Xiong Lu, Hanqing Ding, Jia Luo, Zun-Ji Ke
Heavy alcohol exposure causes profound damage to the adolescent brain, particularly the hippocampus, which underlie some behavioral deficits. However, the underlying molecular mechanisms remain inconclusive. The current study sought to determine whether binge alcohol exposure affects the hippocampus-related behaviors and key signaling proteins that may mediate alcohol neurotoxicity in adolescent rats. Alcohol exposure reduced the number of both NeuN-positive and doublecortin-positive cells in the hippocampus...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29447858/intrathecal-injection-of-scaav9-higf1-prolongs-the-survival-of-als-model-mice-by-inhibiting-the-nf-kb-pathway
#3
HaoJie Hu, HuiQian Lin, WeiSong Duan, Can Cui, ZhongYao Li, YaKun Liu, Wan Wang, Di Wen, Ying Wang, ChunYan Li
Amyotrophic lateral sclerosis (ALS) is a chronic, fatal neurodegenerative disorder characterized by the progressive loss of upper and lower motor neurons. Currently, there is no effective drug for ALS. Recent studies in ALS model mice have shown that insulin-like growth factor-1 (IGF1) may be a promising therapeutic drug. We demonstrate that self-complementary adeno-associated virus serum type 9 encoding the human IGF1 (scAAV9-hIGF1) could significantly postpone the onset and slow down the progression of the disease owning to inhibiting the NF-κB signalling pathway...
February 12, 2018: Neuroscience
https://www.readbyqxmd.com/read/29446722/herbal-compounds-with-special-reference-to-gastrodin-as-potential-therapeutic-agents-for-microglia-mediated-neuroin%C3%AF-ammation
#4
Juan-Juan Li, Shun-Jin Liu, Xiao-Yu Liu, Eng-Ang Ling
BACKGROUND: Activated microglia play a pivotal role neurodegenerative diseases by producing a variety of proinflammatory mediators including tumor necrosis factor-alpha (TNF-α), interleukin-1bea (IL-1β) and nitric oxide (NO) that are toxic to neurons and oligodendrocytes. METHODS: In view of the above, suppression of microglia mediated neuroinflammation is deemed a therapeutic strategy for neurodegenerative diseases. Several potential Chinese herbal extracts have been reported to exert neuroprotective effects against neurodegenerative diseases targeting specifically at the activated microglia...
February 14, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29445154/interleukin-4-modulates-microglia-homeostasis-and-attenuates-the-early-slowly-progressive-phase-of-amyotrophic-lateral-sclerosis
#5
Chiara Rossi, Melania Cusimano, Martina Zambito, Annamaria Finardi, Alessia Capotondo, Jose Manuel Garcia-Manteiga, Giancarlo Comi, Roberto Furlan, Gianvito Martino, Luca Muzio
Microglia activation is a commonly pathological hallmark of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), a devastating disorder characterized by a selective motor neurons degeneration. Whether such activation might represent a causal event rather than a secondary epiphenomenon remains elusive. Here, we show that CNS-delivery of IL-4-via a lentiviral-mediated gene therapy strategy-skews microglia to proliferate, inducing these cells to adopt the phenotype of slowly proliferating cells...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29443098/a-novel-in-vitro-live-imaging-assay-of-astrocyte-mediated-phagocytosis-using-ph-indicator-conjugated-synaptosomes
#6
Youkyeong Gloria Byun, Won-Suk Chung
Astrocytes are the major cell type in the brain and directly contact synapses and blood vessels. Although microglial cells have been considered the major immune cells and only phagocytes in the brain, recent studies have shown that astrocytes also participate in various phagocytic processes, such as developmental synapse elimination and clearance of amyloid beta plaques in Alzheimer's disease (AD). Despite these findings, the efficiency of astrocyte engulfment and degradation of their targets is unclear compared with that of microglia...
February 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29433896/generating-tissue-resident-macrophages-from-pluripotent-stem-cells-lessons-learned-from-microglia
#7
Christel Claes, Johanna Van den Daele, Catherine M Verfaillie
Over the past decades, the importance of the immune system in a broad scope of pathologies, has drawn attention towards tissue-resident macrophages, such as microglia in the brain. To enable the study of for instance microglia, it is crucial to recreate in vitro (and in vivo) assays. However, very fast loss of tissue-specific features of primary tissue resident macrophages, including microglia, upon in vitro culture has complicated such studies. Moreover, limited knowledge of macrophage developmental pathways and the role of local 'niche factors', has hampered the generation of tissue-resident macrophages from pluripotent stem cells (PSC)...
February 2, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29433522/ros-responsive-resveratrol-delivery-from-ldlr-peptide-conjugated-pla-coated-mesoporous-silica-nanoparticles-across-the-blood-brain-barrier
#8
Yang Shen, Bin Cao, Noah R Snyder, Kevin M Woeppel, James R Eles, Xinyan Tracy Cui
BACKGROUND: Oxidative stress acts as a trigger in the course of neurodegenerative diseases and neural injuries. An antioxidant-based therapy can be effective to ameliorate the deleterious effects of oxidative stress. Resveratrol (RSV) has been shown to be effective at removing excess reactive oxygen species (ROS) or reactive nitrogen species generation in the central nervous system (CNS), but the delivery of RSV into the brain through systemic administration is inefficient. Here, we have developed a RSV delivery vehicle based on polylactic acid (PLA)-coated mesoporous silica nanoparticles (MSNPs), conjugated with a ligand peptide of low-density lipoprotein receptor (LDLR) to enhance their transcytosis across the blood-brain barrier (BBB)...
February 13, 2018: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/29433360/ampk-nrf2-signaling-is-involved-in-the-anti-neuroinflammatory-action-of-petatewalide-b-from-petasites-japonicus-against-lipopolysaccharides-in-microglia
#9
Sun Young Park, Min Hyun Choi, Mei Li, Ke Li, Geuntae Park, Young-Whan Choi
OBJECTIVES: Abnormal microglia secrete neuroinflammatory factors that play a pivotal role in neurodegenerative-disorder development. Thus, regulating abnormal microglia-activation could be a promising therapeutic strategy. The purposes of this study included investigating the effect of Petatewalide B on lipopolysaccharide- (LPS-) stimulated microglia and exploring the role of the AMPK/Nrf2- (adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2) signaling pathway in the anti-neuroinflammatory function of Petatewalide B...
February 12, 2018: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/29427792/s-glutathionylation-exerts-opposing-roles-in-the-regulation-of-stat1-and-stat3-signaling-in-reactive-microglia
#10
Elena Butturini, Flora Cozzolino, Diana Boriero, Alessandra Carcereri de Prati, Maria Monti, Michele Rossin, Diana Canetti, Barbara Cellini, Piero Pucci, Sofia Mariotto
STAT1 and STAT3 are two transcription factors involved in a lot of cellular functions such as immune response, proliferation, apoptosis, and cell survival. A number of literature evidences described a yin-yang relationship between activation of STAT1 and STAT3 in neurodegenerative disorders where STAT1 exerts a pro-apoptotic effect whereas STAT3 shows neuroprotective properties through the inhibition of apoptosis. Although the role of oxidative-stress in the pathogenesis of neurodegeneration is clearly described, its influence in the regulation of these pathways is poorly understood...
February 7, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29427657/the-evolving-dialogue-of-microglia-and-neurons-in-alzheimer-s-disease-microglia-as-necessary-transducers-of-pathology
#11
REVIEW
E Simon, J Obst, D Gomez-Nicola
The understanding of the contribution of microglial cells to the onset and/or progression chronic neurodegenerative diseases is key to identify disease-modifying therapies, given the strong neuroimmune component of these disorders. In this review, we dissect the different pathways by which microglia can affect, directly or indirectly, neuronal function and dysfunction associated with diseases like Alzheimer's. We here present the rationale for proposing a model to explain the contribution of microglia to the pathophysiology of Alzheimer's disease, defining microglial cells as necessary transducers of pathology and ideal targets for intervention...
February 7, 2018: Neuroscience
https://www.readbyqxmd.com/read/29427085/regulatory-effects-of-neuroinflammatory-responses-through-brain-derived-neurotrophic-factor-signaling-in-microglial-cells
#12
Sheng-Wei Lai, Jia-Hong Chen, Hsiao-Yun Lin, Yu-Shu Liu, Cheng-Fang Tsai, Pei-Chun Chang, Dah-Yuu Lu, Chingju Lin
Inhibition of microglial over-activation is an important strategy to counter balance neurodegenerative progression. We previously demonstrated that the adenosine monophosphate-activated protein kinase (AMPK) may be a therapeutic target in mediating anti-neuroinflammatory responses in microglia. Brain-derived neurotrophic factor (BDNF) is one of the major neurotrophic factors produced by astrocytes to maintain the development and survival of neurons in the brain, and have recently been shown to modulate homeostasis of neuroinflammation...
February 9, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29425760/agathisflavone-a-flavonoid-derived-from-poincianella-pyramidalis-tul-enhances-neuronal-population-and-protects-against-glutamate-excitotoxicity
#13
Cleide Dos Santos Souza, Maria Socorro Grangeiro, Erica Patricia Lima Pereira, Cleonice Creusa Dos Santos, Alessandra Bispo da Silva, Geraldo Pedral Sampaio, Daiana Dias Ribeiro Figueiredo, Jorge Mauricio David, Juceni Pereira David, Victor Diogenes Amaral da Silva, Arthur Morgan Butt, Silvia Lima Costa
Flavonoids are bioactive compounds that are known to be neuroprotective against glutamate-mediated excitotoxicity, one of the major causes of neurodegeneration. The mechanisms underlying these effects are unresolved, but recent evidence indicates flavonoids may modulate estrogen signaling, which can delay the onset and ameliorate the severity of neurodegenerative disorders. Furthermore, the roles played by glial cells in the neuroprotective effects of flavonoids are poorly understood. The aim of this study was to investigate the effects of the flavonoid agathisflavone (FAB) in primary neuron-glial co-cultures from postnatal rat cerebral cortex...
February 6, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29424844/dietary-lipophilic-iron-alters-amyloidogenesis-and-microglial-morphology-in-alzheimer-s-disease-knock-in-app-mice
#14
Douglas G Peters, Alexis N Pollack, Keith C Cheng, Dongxiao Sun, Takaomi Saido, Michael P Haaf, Qing X Yang, James R Connor, Mark D Meadowcroft
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized pathologically by amyloid beta (Aβ) deposition, microgliosis, and iron dyshomeostasis. Increased labile iron due to homeostatic dysregulation is believed to facilitate amyloidogenesis. Free iron is incorporated into aggregating amyloid peptides during Aβ plaque formation and increases potential for oxidative stress surrounding plaques. The goal of this work was to observe how brain iron levels temporally influence Aβ plaque formation, plaque iron concentration, and microgliosis...
February 9, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29416036/a-transcriptomic-atlas-of-aged-human-microglia
#15
Marta Olah, Ellis Patrick, Alexandra-Chloe Villani, Jishu Xu, Charles C White, Katie J Ryan, Paul Piehowski, Alifiya Kapasi, Parham Nejad, Maria Cimpean, Sarah Connor, Christina J Yung, Michael Frangieh, Allison McHenry, Wassim Elyaman, Vlad Petyuk, Julie A Schneider, David A Bennett, Philip L De Jager, Elizabeth M Bradshaw
With a rapidly aging global human population, finding a cure for late onset neurodegenerative diseases has become an urgent enterprise. However, these efforts are hindered by the lack of understanding of what constitutes the phenotype of aged human microglia-the cell type that has been strongly implicated by genetic studies in the pathogenesis of age-related neurodegenerative disease. Here, we establish the set of genes that is preferentially expressed by microglia in the aged human brain. This HuMi_Aged gene set captures a unique phenotype, which we confirm at the protein level...
February 7, 2018: Nature Communications
https://www.readbyqxmd.com/read/29413519/imaging-translocator-protein-as-a-biomarker-of-neuroinflammation-in-dementia
#16
William C Kreisl, Ioline D Henter, Robert B Innis
Neuroinflammation has long been considered a potential contributor to neurodegenerative disorders that result in dementia. Accumulation of abnormal protein aggregates in Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies is associated with the activation of microglia and astrocytes into proinflammatory states, and chronic low-level activation of glial cells likely contributes to the pathological changes observed in these and other neurodegenerative diseases. The 18kDa translocator protein (TSPO) is a key biomarker for measuring inflammation in the brain via positron emission tomography (PET)...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29409838/deciphering-the-microstructure-of-hippocampal-subfields-with-in-vivo-dti-and-noddi-applications-to-experimental-multiple-sclerosis
#17
Amandine Crombe, Vincent Planche, Gerard Raffard, Julien Bourel, Nadège Dubourdieu, Aude Panatier, Hikaru Fukutomi, Vincent Dousset, Stephane Oliet, Bassem Hiba, Thomas Tourdias
The hippocampus contains distinct populations of neurons organized into separate anatomical subfields and layers with differential vulnerability to pathological mechanisms. The ability of in vivo neuroimaging to pinpoint regional vulnerability is especially important for better understanding of hippocampal pathology at the early stage of neurodegenerative disorders and for monitoring future therapeutic strategies. This is the case for instance in multiple sclerosis whose neurodegenerative component can affect the hippocampus from the early stage...
January 31, 2018: NeuroImage
https://www.readbyqxmd.com/read/29408508/role-of-lrrk2-in-manganese-induced-neuroinflammation-and-microglial-autophagy
#18
Jiayan Chen, Peng Su, Wenjing Luo, Jingyuan Chen
Overexposure to manganese (Mn) leads to manganism and neurotoxicity induced by Mn is the focus of recent research. Microglia play a vital role in Mn-induced neurotoxicity, and our previous studies firstly showed that Mn could stimulate activation of microglia, leading to the neuroinflammation, and inhibition of microglial inflammation effectively attenuated Mn-induced death of dopamine neurons. However, the detailed mechanism of manganese-induced neuroinflammation is still unclear. Leucine rich repeat kinase 2 (LRRK2) is a key molecule in the pathogenesis of many neurodegenerative disorders...
February 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29406909/neuroinflammation-following-disease-modifying-therapy-in-multiple-sclerosis-a-pilot-positron-emission-tomography-study
#19
Tomoyasu Bunai, Tatsuhiro Terada, Satoshi Kono, Masamichi Yokokura, Etsuji Yoshikawa, Masami Futatsubashi, Hiroaki Miyajima, Yasuomi Ouchi
INTRODUCTION: Chronic activation of microglia accelerates the neurodegenerative process in multiple sclerosis (MS). Although disease modifying therapy (DMT) is reportedly effective for neuroinflammatory responses in MS, the progression of neuroinflammation after DMT remains unclear. METHODS: We evaluated microglial activation in six clinically stable relapsing-remitting MS patients after DMT by quantifying changes in translocator protein (TSPO) density using PET with [11C]DPA713, a selective TSPO tracer for microglial activation...
February 15, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29401686/evaluation-of-polyphenol-anthocyanin-enriched-extracts-of-blackberry-black-raspberry-blueberry-cranberry-red-raspberry-and-strawberry-for-free-radical-scavenging-reactive-carbonyl-species-trapping-anti-glycation-anti-%C3%AE-amyloid-aggregation-and-microglial-neuroprotective
#20
Hang Ma, Shelby L Johnson, Weixi Liu, Nicholas A DaSilva, Susan Meschwitz, Joel A Dain, Navindra P Seeram
Glycation is associated with several neurodegenerative disorders, including Alzheimer's disease (AD), where it potentiates the aggregation and toxicity of proteins such as β-amyloid (Aβ). Published studies support the anti-glycation and neuroprotective effects of several polyphenol-rich fruits, including berries, which are rich in anthocyanins. Herein, blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts were evaluated for: (1) total phenolic and anthocyanins contents, (2) free radical (DPPH) scavenging and reactive carbonyl species (methylglyoxal; MGO) trapping, (3) anti-glycation (using BSA-fructose and BSA-MGO models), (4) anti-Aβ aggregation (using thermal- and MGO-induced fibrillation models), and, (5) murine microglia (BV-2) neuroprotective properties...
February 3, 2018: International Journal of Molecular Sciences
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