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Astrocyte activation

Chye Soi Moi, Chia Kin Yen, Khuen Yen Ng, Koh Rhun Yian
Protein misfolding and aggregation have been considered the common pathological hallmarks for a number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). These abnormal proteins aggregation damage mitochondria and induce oxidative stress and resulting neuronal cell death. Prolong neuronal damage activates microglia and astrocytes, development of inflammation reaction and further promotes neurodegeneration. Thus, elimination of abnormal proteins aggregation without eliciting any adverse effects are the main treatment strategies...
March 15, 2018: CNS & Neurological Disorders Drug Targets
Marija Adzic, Nadezda Nedeljkovic
CD73 is a bifunctional glycosylphosphatidylinositol (GPI)-anchored membrane protein which functions as ecto-5'-nucleotidase and a membrane receptor for extracellular matrix protein (ECM). A large body of evidence demonstrates a critical involvement of altered purine metabolism and particularly, increased expression of CD73 in a number of human disorders, including cancer and immunodeficiency. Massive up-regulation of CD73 was also found in reactive astrocytes in several experimental models of human neuropathologies...
2018: Frontiers in Pharmacology
Yoshitoshi Kasuya, Hiroki Umezawa, Masahiko Hatano
Spinal cord injury (SCI) consists of three phases-acute, secondary, and chronic damages-and limiting the development of secondary damage possibly improves functional recovery after SCI. A major component of the secondary phase of SCI is regarded as inflammation-triggered events: induction of cytokines, edema, microglial activation, apoptosis of cells including oligodendrocytes and neurons, demyelination, formation of the astrocytic scar, and so on. Two major stress-activated protein kinases (SAPKs)-c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK)-are activated in various types of cells in response to cellular stresses such as apoptotic stimuli and inflammatory waves...
March 15, 2018: International Journal of Molecular Sciences
Caitlin A Wotton, Elizabeth F Quon, Ashley C Palmer, Lane K Bekar
Both serotonin (5HT) and stress exert changes in cortical inhibitory tone to shape activity of cortical networks. As astrocytes are also known to affect inhibition through established purinergic pathways, we assessed the role of GABA and purinergic pathways in rapid corticosterone (CORT) and 5HT effects on cortical inhibition. We used a paired-pulse paradigm (P1 & P2) in acutely isolated mouse brain slices to evaluate changes in cortical evoked inhibition. Normally, 5HT decreases amplitude of the first pulse P1, while increasing the amplitude of P2 (increase frequency transmission)...
March 15, 2018: Journal of Neuroendocrinology
Adrienne M Antonson, Bindu Balakrishnan, Emily C Radlowski, Geraldine Petr, Rodney W Johnson
Maternal infection during pregnancy increases the risk of neurobehavioral problems in offspring. Evidence from rodent models indicates that the maternal immune response to infection can alter fetal brain development, particularly in the hippocampus. However, information on the effects of maternal viral infection on fetal brain development in gyrencephalic species is limited. Thus, the objective of this study was to assess several effects of maternal viral infection in the last one-third of gestation on hippocampal gene expression and development in fetal piglets...
March 14, 2018: Developmental Neuroscience
Yin-Feng Dong, Ruo-Bing Guo, Juan Ji, Lu-Lu Cao, Ling Zhang, Zheng-Zhen Chen, Ji-Ye Huang, Jin Wu, Jun Lu, Xiu-Lan Sun
Fingolimod (FTY720) is used as an immunosuppressant for multiple sclerosis. Numerous studies indicated its neuroprotective effects in stroke. However, the mechanism remains to be elucidated. This study was intended to investigate the mechanisms of phosphorylated FTY720 (pFTY720), which was the principle active molecule in regulating astrocyte-mediated inflammatory responses induced by oxygen-glucose deprivation (OGD). Results demonstrated that pFTY720 could protect astrocytes against OGD-induced injury and inflammatory responses...
March 13, 2018: Journal of Cellular and Molecular Medicine
Boldizsár Czéh, Szilvia A Nagy
Depressive disorders are complex, multifactorial mental disorders with unknown neurobiology. Numerous theories aim to explain the pathophysiology. According to the "gliocentric theory", glial abnormalities are responsible for the development of the disease. The aim of this review article is to summarize the rapidly growing number of cellular and molecular evidences indicating disturbed glial functioning in depressive disorders. We focus here exclusively on the clinical studies and present the in vivo neuroimaging findings together with the postmortem molecular and histopathological data...
2018: Frontiers in Molecular Neuroscience
Peng Jin, Seung-Hyun Shin, Yang-Sook Chun, Hyun-Woo Shin, Yong Jae Shin, Yeri Lee, Donggeon Kim, Do-Hyun Nam, Jong-Wan Park
During tumor development, stromal cells are co-opted to the tumor milieu and provide favorable conditions for the tumor. Hypoxia stimulates cancer cells to acquire a more malignant phenotype via activation of hypoxia-inducible factor 1 (HIF-1). Given that cancer cells and astrocytes in glioblastomas coexist in a hypoxic microenvironment, we examined whether astrocytes affect the adaptation of glioblastoma cells to hypoxia. Immunoblotting, reporter assays, quantitative RT-PCR, and chromatin immunoprecipitation were performed to evaluate HIF-1 signaling in glioblastoma cells...
March 14, 2018: Oncogene
Reza Naeimi, Fatemeh Safarpour, Mona Hashemian, Hamed Tashakorian, Seyed Raheleh Ahmadian, Manouchehr Ashrafpour, Maryam Ghasemi-Kasman
Curcumin has been introduced as effective anti-inflammatory agent in treatment of several inflammatory disorders. Despite the wide range pharmacological activities, clinical application of curcumin is restricted mainly due to the low water solubility of this substance. More recently, we could remarkably improve the aqueous solubility of curcumin by its encapsulation in chitosan-alginate-sodium tripolyphosphate nanoparticles (CS-ALG-STPP NPs). In this study, the anti-inflammatory and myelin protective effects of curcumin-loaded NPs were evaluated in lysolecithin (LPC)-induced focal demyelination model...
March 9, 2018: Neuroscience Letters
D Calvetti, G Capo Rangel, L Gerardo Giorda, E Somersalo
The human brain is a small organ which uses a disproportional amount of the total metabolic energy production in the body. While it is well understood that the most significant energy sink is the maintenance of the neuronal membrane potential during the brain signaling activity, the role of astrocytes in the energy balance continues to be the topic of a lot of research. A key function of astrocytes, besides clearing glutamate from the synaptic clefts, is the potassium clearing after neuronal activation. Extracellular potassium plays a significant role in triggering neuronal firing, and elevated concentration of potassium may lead to abnormal firing pattern, e...
March 9, 2018: Journal of Theoretical Biology
Lorena Colás, Maria Domercq, Pedro Ramos-Cabrer, Ana Palma, Vanessa Gómez-Vallejo, Daniel Padro, Sandra Plaza-García, Krishna R Pulagam, Makoto Higuchi, Carlos Matute, Jordi Llop, Abraham Martín
In vivo positron emission tomography (PET) imaging of nicotinic acetylcholine receptors (nAChRs) is a promising tool for the imaging evaluation of neurologic and neurodegenerative diseases. However, the role of α7 nAChRs after brain diseases such as cerebral ischemia and its involvement in inflammatory reaction is still largely unknown. In vivo and ex vivo evaluation of α7 nAChRs expression after transient middle cerebral artery occlusion (MCAO) was carried out using PET imaging with [11 C]NS14492 and immunohistochemistry (IHC)...
March 12, 2018: Glia
Xiaoxu Chen, Xiaoke Nie, Jiamin Mao, Yan Zhang, Kaizhi Yin, Shengyang Jiang
Perfluorooctanesulfonate (PFOS)-containing compounds are widely used in all aspects of industrial and consumer products. Recent studies indicated that PFOS is ubiquitous in environments and is considered to be a new type of persistent organic pollutant (POP). This has raised concerns regarding its adverse effects on human health. The nervous system is regarded as a sensitive target of environmental contaminants, including PFOS. Previous findings showed that PFOS can induce neurobehavioral deficits. However, the molecular mechanism underlying PFOS neurotoxicity remains obscure...
March 8, 2018: Neurotoxicology
Vladimir Kepe, Claudio Scafoglio, Jie Liu, William H Yong, Marvin Bergsneider, Sung-Cheng Huang, Jorge R Barrio, Ernest M Wright
A novel glucose transporter, the sodium glucose cotransporter 2 (SGLT2), has been demonstrated to contribute to the demand for glucose by pancreatic and prostate tumors, and its functional activity has been imaged using a SGLT specific PET imaging probe, α-methyl-4-[F-18]fluoro-4-deoxy-D-glucopyaranoside (Me-4FDG). In this study, Me-4FDG PET was extended to evaluate patients with high-grade astrocytic tumors. Me-4FDG PET scans were performed in four patients diagnosed with WHO Grade III or IV astrocytomas and control subjects, and compared with 2-deoxy-2-[F-18]fluoro-D-glucose (2-FDG) PET and magnetic resonance imaging (MRI) of the same subjects...
March 10, 2018: Journal of Neuro-oncology
Christopher G Hughes, Mayur B Patel, Nathan E Brummel, Jennifer L Thompson, J Brennan McNeil, Pratik P Pandharipande, James C Jackson, Rameela Chandrasekhar, Lorraine B Ware, E Wesley Ely, Timothy D Girard
PURPOSE: Neurologic and endothelial injury biomarkers are associated with prolonged delirium during critical illness and may reflect injury pathways that lead to poor long-term outcomes. We hypothesized that blood-brain barrier (BBB), neuronal, and endothelial injury biomarkers measured during critical illness are associated with cognitive impairment and disability after discharge. METHODS: We enrolled adults with respiratory failure and/or shock and measured plasma concentrations of BBB (S100B), neuronal (UCHL1, BDNF), and endothelial (E-selectin, PAI-1) injury markers within 72 h of ICU admission...
March 9, 2018: Intensive Care Medicine
Valentin Mutemberezi, Baptiste Buisseret, Julien Masquelier, Owein Guillemot-Legris, Mireille Alhouayek, Giulio G Muccioli
BACKGROUND: Oxysterols are cholesterol derivatives that have been suggested to play a role in inflammatory diseases such as obesity, atherosclerosis, or neuroinflammatory diseases. However, the effect of neuroinflammation on oxysterol levels has only been partially studied so far. METHODS: We used an HPLC-MS method to quantify over ten oxysterols both in in vitro and in vivo models of neuroinflammation. In the same models, we used RT-qPCR to analyze the expression of the enzymes responsible for oxysterol metabolism...
March 9, 2018: Journal of Neuroinflammation
Luca Bors, Kinga Tóth, Estilla Zsófia Tóth, Ágnes Bajza, Attila Csorba, Krisztián Szigeti, Domokos Máthé, Gábor Perlaki, Gergely Orsi, Gábor K Tóth, Franciska Erdő
Decreased beta-amyloid clearance in Alzheimer's disease and increased blood-brain barrier permeability in aged subjects have been reported in several articles. However, morphological and functional characterization of blood-brain barrier and its membrane transporter activity have not been described in physiological aging yet. The aim of our study was to explore the structural changes in the brain microvessels and possible functional alterations of P-glycoprotein at the blood-brain barrier with aging. Our approach included MR imaging for anatomical orientation in middle aged rats, electronmicroscopy and immunohistochemistry to analyse the alterations at cellular level, dual or triple-probe microdialysis and SPECT to test P-glycoprotein functionality in young and middle aged rats...
March 6, 2018: Brain Research Bulletin
J L Hawkins, N J Moore, D Miley, P L Durham
The pathology of migraine, a common neurological disease, involves sensitization and activation of trigeminal nociceptive neurons to promote hyperalgesia and allodynia during an attack. Migraineurs often exhibit characteristics of a hyperexcitable or hypervigilant nervous system. One of the primary reported risk factors for development of a hyperexcitable trigeminal system is chronic, unmanaged stress and anxiety. While primary traumatic stress is a commonly cited risk factor for many pain conditions, exposure to secondary traumatic stress early in life is also thought to be a contributing risk factor...
March 6, 2018: Brain Research
Reut Hilu-Dadia, Ketty Hakim-Mishnaevski, Flonia Levy-Adam, Estee Kurant
Development of the central nervous system involves elimination of superfluous neurons through apoptosis and subsequent phagocytosis. In Drosophila, this occurs mainly during three developmental stages: embryogenesis, metamorphosis and emerging adult. Two transmembrane glial phagocytic receptors, SIMU (homolog of the mammalian Stabilin-2) and Draper (homolog of the mammalian MEGF10 and Jedi), mediate glial phagocytosis of apoptotic neurons during embryogenesis. However, less is known about the removal of apoptotic neurons during later stages of development...
March 9, 2018: Glia
A Belin-Rauscent, J Lacoste, O Hermine, A Moussy, B J Everitt, David Belin
RATIONALE: Accumulating evidence shows that cocaine, and also heroin, influence several tyrosine kinases, expressed in neurons and in non-neuronal populations such as microglia, astrocytes and mast-cells. Drug-induced activation of mast cells both triggers inflammatory processes in the brain mediated by the glial cells they activate, and facilitates histamine release which may directly influence the dopamine system. Thus, by triggering the activation and degranulation of mast cells dependent on the tyrosine kinase c-kit and Fyn, the latter being also involved in NMDA-dependent synaptic plasticity, cocaine and heroin may indirectly influence the neural mechanisms that mediate their reinforcing properties...
March 8, 2018: Psychopharmacology
Carlos R Dostal, Megan Carson Sulzer, Keith W Kelley, Gregory G Freund, Robert H McCusker
Stressors activate the hypothalamic-pituitary-adrenal (HPA) axis and immune system eliciting changes in cognitive function, mood and anxiety. An important link between stress and altered behavior is stimulation of the Kynurenine Pathway which generates neuroactive and immunomodulatory kynurenines. Tryptophan entry into this pathway is controlled by rate-limiting indoleamine/tryptophan 2,3-dioxygenases (DOs: Ido1, Ido2, Tdo2). Although implicated as mediating changes in behavior, detecting stress-induced DO expression has proven inconsistent...
December 2017: Neurobiology of Stress
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