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https://www.readbyqxmd.com/read/28346397/the-process-and-regulatory-components-of-inflammation-in-brain-oncogenesis
#1
REVIEW
A G M Mostofa, Surendra R Punganuru, Hanumantha Rao Madala, Mohammad Al-Obaide, Kalkunte S Srivenugopal
Central nervous system tumors comprising the primary cancers and brain metastases remain the most lethal neoplasms and challenging to treat. Substantial evidence points to a paramount role for inflammation in the pathology leading to gliomagenesis, malignant progression and tumor aggressiveness in the central nervous system (CNS) microenvironment. This review summarizes the salient contributions of oxidative stress, interleukins, tumor necrosis factor-α (TNF-α), cyclooxygenases, and transcription factors such as signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and the associated cross-talks to the inflammatory signaling in CNS cancers...
March 27, 2017: Biomolecules
https://www.readbyqxmd.com/read/28346104/bioengineered-3d-glial-cell-culture-systems-and-applications-for-neurodegeneration-and-neuroinflammation
#2
P Marc D Watson, Edel Kavanagh, Gary Allenby, Matthew Vassey
Neurodegeneration and neuroinflammation are key features in a range of chronic central nervous system (CNS) diseases such as Alzheimer's and Parkinson's disease, as well as acute conditions like stroke and traumatic brain injury, for which there remains significant unmet clinical need. It is now well recognized that current cell culture methodologies are limited in their ability to recapitulate the cellular environment that is present in vivo, and there is a growing body of evidence to show that three-dimensional (3D) culture systems represent a more physiologically accurate model than traditional two-dimensional (2D) cultures...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345587/derivation-of-functional-human-astrocytes-from-cerebral-organoids
#3
Rômulo Sperduto Dezonne, Rafaela Costa Sartore, Juliana Minardi Nascimento, Verônica M Saia-Cereda, Luciana Ferreira Romão, Soniza Vieira Alves-Leon, Jorge Marcondes de Souza, Daniel Martins-de-Souza, Stevens Kastrup Rehen, Flávia Carvalho Alcantara Gomes
Astrocytes play a critical role in the development and homeostasis of the central nervous system (CNS). Astrocyte dysfunction results in several neurological and degenerative diseases. However, a major challenge to our understanding of astrocyte physiology and pathology is the restriction of studies to animal models, human post-mortem brain tissues, or samples obtained from invasive surgical procedures. Here, we report a protocol to generate human functional astrocytes from cerebral organoids derived from human pluripotent stem cells...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345117/inwardly-rectifying-k-currents-in-cultured-oligodendrocytes-from-rat-optic-nerve-are-insensitive-to-ph
#4
Alberto Pérez-Samartín, Edith Garay, Juan Pablo H Moctezuma, Abraham Cisneros-Mejorado, María Victoria Sánchez-Gómez, Guadalupe Martel-Gallegos, Leticia Robles-Martínez, Manuel Canedo-Antelo, Carlos Matute, Rogelio O Arellano
Inwardly rectifying K(+) (Kir) channel expression signals at an advanced stage of maturation during oligodendroglial differentiation. Knocking down their expression halts the generation of myelin and produces severe abnormalities in the central nervous system. Kir4.1 is the main subunit involved in the tetrameric structure of Kir channels in glial cells; however, the precise composition of Kir channels expressed in oligodendrocytes (OLs) remains partially unknown, as participation of other subunits has been proposed...
March 27, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28344667/m%C3%A3-ller-cells-and-retinal-axons-can-be-primary-targets-in-experimental-neuromyelitis-optica-spectrum-disorder
#5
REVIEW
Bleranda Zeka, Hans Lassmann, Monika Bradl
Recent work from our laboratory, using different models of experimental neuromyelitis optica spectrum disorder (NMOSD), has led to a number of observations that might be highly relevant for NMOSD patients. For example: (i) in the presence of neuromyelitis optica immunoglobulin G, astrocyte-destructive lesions can be initiated by CD4+ T cells when these cells recognize aquaporin 4 (AQP4), but also when they recognize other antigens of the central nervous system. The only important prerequisite is that the T cells have to be activated within the central nervous system by "their" specific antigen...
January 2017: Clinical & Experimental Neuroimmunology
https://www.readbyqxmd.com/read/28344005/mir-342-5p-regulates-neural-stem-cell-proliferation-and-differentiation-downstream-to-notch-signaling-in-mice
#6
Fang Gao, Yu-Fei Zhang, Zheng-Ping Zhang, Luo-An Fu, Xiu-Li Cao, Yi-Zhe Zhang, Chen-Jun Guo, Xian-Chun Yan, Qin-Chuan Yang, Yi-Yang Hu, Xiang-Hui Zhao, Ya-Zhou Wang, Sheng-Xi Wu, Gong Ju, Min-Hua Zheng, Hua Han
Notch signaling is critically involved in neural development, but the downstream effectors remain incompletely understood. In this study, we cultured neurospheres from Nestin-Cre-mediated conditional Rbp-j knockout (Rbp-j cKO) and control embryos and compared their miRNA expression profiles using microarray. Among differentially expressed miRNAs, miR-342-5p showed upregulated expression as Notch signaling was genetically or pharmaceutically interrupted. Consistently, the promoter of the miR-342-5p host gene, the Ena-vasodilator stimulated phosphoprotein-like (Evl), was negatively regulated by Notch signaling, probably through HES5...
March 15, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28344003/abnormal-neural-progenitor-cells-differentiated-from-induced-pluripotent-stem-cells-partially-mimicked-development-of-tsc2-neurological-abnormalities
#7
Yaqin Li, Jiqing Cao, Menglong Chen, Jing Li, Yiming Sun, Yu Zhang, Yuling Zhu, Liang Wang, Cheng Zhang
Tuberous sclerosis complex (TSC) is a disease featuring devastating and therapeutically challenging neurological abnormalities. However, there is a lack of specific neural progenitor cell models for TSC. Here, the pathology of TSC was studied using primitive neural stem cells (pNSCs) from a patient presenting a c.1444-2A>C mutation in TSC2. We found that TSC2 pNSCs had higher proliferative activity and increased PAX6 expression compared with those of control pNSCs. Neurons differentiated from TSC2 pNSCs showed enlargement of the soma, perturbed neurite outgrowth, and abnormal connections among cells...
March 15, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28344002/establishment-of-a-human-blood-brain-barrier-co-culture-model-mimicking-the-neurovascular-unit-using-induced-pluri-and-multipotent-stem-cells
#8
Antje Appelt-Menzel, Alevtina Cubukova, Katharina Günther, Frank Edenhofer, Jörg Piontek, Gerd Krause, Tanja Stüber, Heike Walles, Winfried Neuhaus, Marco Metzger
In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm(2) and distinct upregulation of typical BBB genes...
March 22, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28343966/astrocytes-regulate-daily-rhythms-in-the-suprachiasmatic-nucleus-and-behavior
#9
Chak Foon Tso, Tatiana Simon, Alison C Greenlaw, Tanvi Puri, Michihiro Mieda, Erik D Herzog
Astrocytes are active partners in neural information processing [1, 2]. However, the roles of astrocytes in regulating behavior remain unclear [3, 4]. Because astrocytes have persistent circadian clock gene expression and ATP release in vitro [5-8], we hypothesized that they regulate daily rhythms in neurons and behavior. Here, we demonstrated that daily rhythms in astrocytes within the mammalian master circadian pacemaker, the suprachiasmatic nucleus (SCN), determine the period of wheel-running activity. Ablating the essential clock gene Bmal1 specifically in SCN astrocytes lengthened the circadian period of clock gene expression in the SCN and in locomotor behavior...
March 18, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28343073/breviscapine-confers-a-neuroprotective-efficacy-against-transient-focal-cerebral-ischemia-by-attenuating-neuronal-and-astrocytic-autophagy-in-the-penumbra
#10
Zhang Pengyue, Guo Tao, He Hongyun, Yang Liqiang, Deng Yihao
Breviscapine is a flavonoid derived from a traditional Chinese herb Erigerin breviscapus (Vant.) Hand-Mazz, and has been extensively used in clinical treatment for cerebral stroke in China, but the underlying pharmacological mechanisms are still unclear. In present study, we investigated whether breviscapine could confer a neuroprotection against cerebral ischemia injury by targeting autophagy mechanisms. A cerebral stroke model in Sprague-Dawley rats was prepared by middle cerebral artery occlusion (MCAO), rats were then randomly divided into 5 groups: MCAO+Bre group, rats were treated with breviscapine; MCAO+Tat-Beclin-1 group, animals were administrated with specific autophagy inducer Tat-Beclin-1; MCAO+Bre+Tat-Beclin-1 group, rats were treated with both breviscapine and Tat-Beclin-1, MCAO+saline group, rats received the same volume of physiological saline, and Sham surgery group...
March 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28342971/a-novel-dual-glp-1-gip-receptor-agonist-alleviates-cognitive-decline-by-re-sensitizing-insulin-signaling-in-the-alzheimer-icv-stz-rat-model
#11
Lijuan Shi, Zhihua Zhang, Lin Li, Christian Hölscher
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, accompanied by memory loss and cognitive impairments, and there is no effective treatment for it at present. Since type 2 diabetes (T2DM) has been identified as a risk factor for AD, the incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP), promising antidiabetic agents for the treatment of type 2 diabetes, have been tested in models of neurodegenerative disease including AD and achieved good results...
March 22, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28342896/neuroprotective-and-axonal-outgrowth-promoting-effects-of-tetramethylpyrazine-nitrone-in-chronic-cerebral-hypoperfusion-rats-and-primary-hippocampal-neurons-exposed-to-hypoxia
#12
Tao Zhang, Jianbo Gu, Liangmiao Wu, Ning Li, Yewei Sun, Pei Yu, Yuqiang Wang, Gaoxiao Zhang, Zaijun Zhang
Chronic cerebral hypoperfusion is an important risk factor for vascular dementia and other brain dysfunctions, for which there are currently no effective medications available. We investigated the neuroprotective and axonal outgrowth promoting effects of tetramethylpyrazine nitrone (TBN) in a permanent bilateral occlusion of the common carotid arteries (2VO) rat model and in primary hippocampal neurons exposed to oxygen glucose deprivation (OGD). At 6th week after 2VO, TBN increased the time spent in novel arms in the Y-maze test and improved the discrimination ratio in object reorganization task...
March 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28342868/increased-interleukin-1%C3%AE-and-basic-fibroblast-growth-factor-levels-in-the-cerebrospinal-fluid-during-human-herpesvirus-6b-hhv-6b-encephalitis
#13
Masato Tamai, Nobuyuki Kobayashi, Kazuya Shimada, Naomi Oka, Mayumi Takahashi, Akiko Tanuma, Tomohiro Tanemoto, Hiroyuki Namba, Yoshihiro Saito, Yasuyuki Wada, Aikou Okamoto, Hiroyuki Ida, Kazuhiro Kondo
Human herpesvirus 6B (HHV-6B) causes exanthema subitum in infants and is known to be mildly pathogenic. However, HHV-6B infection can induce febrile seizures in a high percentage of patients, and in rare cases, result in encephalitis. We detected higher levels of interleukin (IL)-1β and basic fibroblast growth factor (bFGF) in the cerebrospinal fluid (CFS) of patients with HHV-6B encephalitis when compared to those in patients with non-HHV-6B-induced febrile seizures. In vitro, IL-1β and bFGF enhanced HHV-6B gene expression in infected U373 astrocytes during the initial and maintenance phases of infection, respectively...
March 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28342781/modulation-of-neuroinflammation-the-role-and-therapeutic-potential-of-transient-receptor-potential-vanilloid-1-in-neuro-immune-axis
#14
REVIEW
Wei-Lin Kong, Yuan-Yuan Peng, Bi-Wen Peng
Transient receptor potential vanilloid type 1 channel (TRPV1), as a ligand-gated non-selective cation channel, has recently been demonstrated to have wide expression in the neuro-immune axis, where its multiple functions occur through regulation of both neuronal and non-neuronal activities. Growing evidence has suggested that TRPV1 is functionally expressed in glial cells, especially in the microglia and astrocytes. Glial cells perform immunological functions in response to pathophysiological challenges through pro-inflammatory or anti-inflammatory cytokines and chemokines in which TRPV1 is involved...
March 22, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28342750/mutation-of-the-caspase-3-cleavage-site-in-the-astroglial-glutamate-transporter-eaat2-delays-disease-progression-and-extends-lifespan-in-the-sod1-g93a-mouse-model-of-als
#15
Lauren Taylor Rosenblum, Shashirekha Shamamandri-Markandaiah, Biswarup Ghosh, Emily Foran, Angelo C Lepore, Piera Pasinelli, Davide Trotti
Downregulation in the astroglial glutamate transporter EAAT2 in amyotrophic lateral sclerosis (ALS) patients and mutant SOD1 mouse models of ALS is believed to contribute to the death of motor neurons by excitotoxicity. We previously reported that caspase-3 cleaves EAAT2 at a unique cleavage consensus site located in its c-terminus domain, a proteolytic cleavage that also occurs in vivo in the mutant SOD1 mouse model of ALS and leads to accumulation of a sumoylated EAAT2 C-Terminus fragment (CTE-SUMO1) beginning around onset of disease...
March 22, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28342553/myelin-changes-in-alexander-disease
#16
U Gómez-Pinedo, M Duran-Moreno, S Sirerol-Piquer, J Matias-Guiu
INTRODUCTION: Alexander disease (AxD) is a type of leukodystrophy. Its pathological basis, along with myelin loss, is the appearance of Rosenthal bodies, which are cytoplasmic inclusions in astrocytes. Mutations in the gene coding for GFAP have been identified as a genetic basis for AxD. However, the mechanism by which these variants produce the disease is not understood. DEVELOPMENT: The most widespread hypothesis is that AxD develops when a gain of function mutation causes an increase in GFAP...
March 22, 2017: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/28341998/ire1-signaling-exacerbates-alzheimer-s-disease-pathogenesis
#17
Claudia Duran-Aniotz, Victor Hugo Cornejo, Sandra Espinoza, Álvaro O Ardiles, Danilo B Medinas, Claudia Salazar, Andrew Foley, Ivana Gajardo, Peter Thielen, Takao Iwawaki, Wiep Scheper, Claudio Soto, Adrian G Palacios, Jeroen J M Hoozemans, Claudio Hetz
Altered proteostasis is a salient feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress and abnormal protein aggregation. ER stress triggers the activation of the unfolded protein response (UPR), a signaling pathway that enforces adaptive programs to sustain proteostasis or eliminate terminally damaged cells. IRE1 is an ER-located kinase and endoribonuclease that operates as a major stress transducer, mediating both adaptive and proapoptotic programs under ER stress...
March 24, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28341892/aquaporin-4-forms-a-macromolecular-complex-with-glutamate-transporter-1-and-mu-opioid-receptor-in-astrocytes-and-participates-in-morphine-dependence
#18
Hui Wang, Shiqi Wang, Kang Zhang, Hua Wang, Liting Lan, Xiaoyun Ma, Xiaoyan Liu, Shuzhuo Zhang, Jianquan Zheng, Xiaoli Wei, Haitao Yan
The water channel aquaporin 4 (AQP4) is abundantly expressed in astrocytes and provides a mechanism by which water permeability of the plasma membrane can be regulated. Evidence suggests that AQP4 is associated with glutamate transporter-1 (GLT-1) for glutamate clearance and contributes to morphine dependence. Previous studies show that AQP4 deficiency changed the mu opioid receptor expression and opioid receptors' characteristics as well. In this study, we focused on whether AQP4 could form macromolecular complex with GLT-1 and mu opioid receptor (MOR) and participates in morphine dependence...
March 24, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28341740/nanomolar-nitric-oxide-concentrations-quickly-and-reversibly-modulate-astrocytic-energy-metabolism
#19
Alejandro San Martín, Robinson Arce-Molina, Alex Galaz, Gustavo Pérez-Guerra, L Felipe Barros
Nitric oxide (NO) is an intercellular messenger involved in multiple bodily functions. Prolonged NO exposure irreversibly inhibits respiration by covalent modification of mitochondrial cytochrome oxidase, a phenomenon of pathological relevance. However, the speed and potency of NO's metabolic effects at physiological concentrations are incompletely characterized. To this end, we set out to investigate the metabolic effects of NO in cultured astrocytes from mice by taking advantage of the high spatiotemporal resolution afforded by genetically-encoded Foerster resonance energy transfer (FRET) nanosensors...
March 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28341478/importance-of-major-histocompatibility-complex-of-class-i-mhc-i-expression-for-astroglial-reactivity-and-stability-of-neural-circuits-in-vitro
#20
André Luis Bombeiro, Rafaela Chitarra Rodrigues Hell, Gustavo Ferreira Simões, Mateus Vidigal de Castro, Alexandre Leite Rodrigues de Oliveira
MHC-I molecules are involved in the antigenic presentation of cytosol-derived peptides to CD8T lymphocytes. In the nervous system, MHC-I expression is low to absent, occurring only during certain phases of development and aging or after injuries. The involvement of MHC-I in synaptic plasticity has been reported and, following lesion, astrocytes become reactive, limiting tissue damage. Such cells also attempt to restore homeostasis by secreting cytokines and neurotrophic factors. Moreover, astrocytes modulate synapse function, by taking up and releasing neurotransmitters and by limiting the synaptic cleft...
March 21, 2017: Neuroscience Letters
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