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astrocytes and neurodegenerative disease

Bernd L Fiebich, Carla Ribeiro Alvares Batista, Soraya Wilke Saliba, Nizar M Yousif, Antonio Carlos Pinheiro de Oliveira
Toll-like receptors (TLRs) are a group of receptors widely distributed in the organism. In the central nervous system, they are expressed in neurons, astrocytes and microglia. Although their involvement in immunity is notorious, different articles have demonstrated their roles in physiological and pathological conditions, including neurodegeneration. There is increasing evidence of an involvement of TLRs, especially TLR2, 4 and 9 in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS)...
2018: Frontiers in Cellular Neuroscience
Kavina Ganapathy, Indrani Datta, Ramesh Bhonde
Dental pulp stem cells (DPSCs) are promising for use in neurodegenerative-diseases because of their neural crest origin. While neuronal differentiation of DPSCs has been shown, their plasticity towards astrocyte-like cells remains to be studied. We aimed to examine differentiation potential of DPSCs to astrocytes and their consequent neuroprotective role towards dopaminergic (DA) neurons under 6-hydroxydopamine (6-OHDA) toxicity. Induction of DPSCs to astrocytes with differentiation factors showed definitive increase in astrocyte-specific markers glial fibrillary acidic protein (GFAP), and excitatory amino acid transporter 2 along with glial calcium-binding protein S100β through FACS and immunofluorescence assays...
October 16, 2018: Molecular Neurobiology
Heejung Chun, Ian Marriott, C Justin Lee, Hansang Cho
Alzheimer's disease (AD) is an irreversible neurodegenerative illness and the exact etiology of the disease remains unknown. It is characterized by long preclinical and prodromal phases with pathological features including an accumulation of amyloid-beta (Aβ) peptides into extracellular Aβ plaques in the brain parenchyma and the formation of intracellular neurofibrillary tangles (NFTs) within neurons as a result of abnormal phosphorylation of microtubule-associated tau proteins. In addition, prominent activation of innate immune cells is also observed and/or followed by marked neuroinflammation...
2018: Frontiers in Neurology
Xin Yi Choo, Jeffrey R Liddell, Mikko T Huuskonen, Alexandra Grubman, Diane Moujalled, Jessica Roberts, Kai Kysenius, Lauren Patten, Hazel Quek, Lotta E Oikari, Clare Duncan, Simon A James, Lachlan E McInnes, David J Hayne, Paul S Donnelly, Eveliina Pollari, Suvi Vähätalo, Katarína Lejavová, Mikko I Kettunen, Tarja Malm, Jari Koistinaho, Anthony R White, Katja M Kanninen
Background: Neuroinflammation and biometal dyshomeostasis are key pathological features of several neurodegenerative diseases, including Alzheimer's disease (AD). Inflammation and biometals are linked at the molecular level through regulation of metal buffering proteins such as the metallothioneins. Even though the molecular connections between metals and inflammation have been demonstrated, little information exists on the effect of copper modulation on brain inflammation. Methods: We demonstrate the immunomodulatory potential of the copper bis(thiosemicarbazone) complex CuII (atsm) in an neuroinflammatory model in vivo and describe its anti-inflammatory effects on microglia and astrocytes in vitro ...
2018: Frontiers in Neuroscience
Katarina Krbot, Peter Hermann, Magdalena Krbot Skorić, Inga Zerr, Diego Sepulveda-Falla, Stefan Goebel, Jakob Matschke, Susanne Krasemann, Markus Glatzel
Activated microglia represent a common pathological feature of neurodegenerative diseases. Sporadic Creutzfeldt-Jakob disease (sCJD) patients show more pronounced microglial activation than Alzheimer's disease (AD) patients. Whether these differences are due to differences in disease kinetics or represent disease-specific changes is unknown. We investigated microglial phenotypes in brains of rapidly progressive AD (rpAD) and sCJD patients matched for clinical presentation, including disease duration. We immunostained the frontal cortex, basal ganglia and cerebellum in 16 patients with rpAD and sCJD using antibodies against markers of microglia and recruited monocytes (ionized calcium-binding adaptor molecule 1, human leukocyte antigen DPQR, Cluster of Differentiation 68), an antibody unique to brain-resident microglia (transmembrane protein 119 (TMEM119)), in addition to antibodies against a marker of astrocytes (glial fibrillary acidic protein), amyloid-β (Aβ) and pathological prion protein...
October 15, 2018: Neuropathology: Official Journal of the Japanese Society of Neuropathology
Hongwei Liu, Ya Hua, Richard F Keep, Guohua Xi
Ceruloplasmin (CP) is an essential ferroxidase that is involved in maintaining iron homeostasis by oxidizing toxic ferrous iron (Fe2+ ) to less-toxic ferric iron (Fe3+ ). CP has been well studied in many neurodegenerative diseases, but there has not been an in-depth investigation in intracerebral hemorrhage (ICH). This research investigated brain CP expression in rats after ICH and the effect of CP on Fe2+ -induced brain injury. This study had two parts: first, rats had injection of autologous blood into the right basal ganglia and the time course of CP expression in the brain examined (protein and mRNA)...
October 12, 2018: Translational Stroke Research
Peng-Peng Jin, Feng Xia, Bin-Fang Ma, Zhen Li, Guo-Feng Zhang, Yan-Chun Deng, Zhi-Lan Tu, Xing-Xing Zhang, Shuang-Xing Hou
N-myc downstream-regulated gene 2 (NDRG2) has been implicated in the development of central nervous system and brain diseases such as brain tumors, ischemic stroke and neurodegenerative disorders. However, it remains unclear that the spatiotemporal distribution of NDRG2 in the human fetal brain. In this study, we examined the expression pattern of NDRG2 in different regions of human fetal brain at 16-28 gestational weeks (GWs) by using RT-PCR, western blot and immunohistochemistry. Firstly, RT-PCR revealed that mRNA of NDRG2 was detected in the human brain regions of fetuses at 16-28 GWs such as medulla oblongata (MdO), mesencephalon (MeE), cerebellum (Cbl), frontal lobe (Fr), ventricular (VZ)/subventricular zone (SVZ) and hippocampus (hip), and the expressions of NDRG2 mRNA in these human fetal brain regions were increased with gestational maturation...
October 9, 2018: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Ju-Young Lee, Jin Han Nam, Youngpyo Nam, Hye Yeon Nam, Gwangho Yoon, Eunhwa Ko, Sang-Bum Kim, Mahealani R Bautista, Christina C Capule, Takaoki Koyanagi, Geoffray Leriche, Hwan Geun Choi, Jerry Yang, Jeongyeon Kim, Hyang-Sook Hoe
BACKGROUND: Neuroinflammation is associated with neurodegenerative diseases, including Alzheimer's disease (AD). Thus, modulating the neuroinflammatory response represents a potential therapeutic strategy for treating neurodegenerative diseases. Several recent studies have shown that dopamine (DA) and its receptors are expressed in immune cells and are involved in the neuroinflammatory response. Thus, we recently developed and synthesized a non-self-polymerizing analog of DA (CA140) and examined the effect of CA140 on neuroinflammation...
October 11, 2018: Journal of Neuroinflammation
Boris Görg, Ayşe Karababa, Dieter Häussinger
Hepatic Encephalopathy (HE) is a severe complication of acute or chronic liver diseases with a broad spectrum of neurological symptoms including motor disturbances and cognitive impairment of different severity. Contrary to former beliefs, a growing number of studies suggest that cognitive impairment may not fully reverse after an acute episode of overt HE in patients with liver cirrhosis. The reasons for persistent cognitive impairment in HE are currently unknown but recent observations raise the possibility that astrocyte senescence may play a role here...
September 2018: Journal of Clinical and Experimental Hepatology
Katarzyna Kuter, Łukasz Olech, Urszula Głowacka, Martyna Paleczna
Glial pathology precedes symptoms of Parkinson's disease (PD) and multiple other neurodegenerative diseases. Prolonged impairment of astrocytic functions could increase the vulnerability of dopaminergic neurons in the substantia nigra (SN), accelerate their degeneration and affect ability to compensate for partial degeneration at the presymptomatic stages of the disease. The aim of this study was to investigate the astrocyte depletion in the SN, its impact on the dopaminergic system functioning and multiple markers of energy metabolism during the early stages of neurodegeneration and compensation...
October 8, 2018: Journal of Neurochemistry
Fangzhou Li, Takashi Ayaki, Takakuni Maki, Nobukatsu Sawamoto, Ryosuke Takahashi
Multiple system atrophy (MSA) is a neurodegenerative disease characterized by parkinsonism, ataxia, and autonomic dysfunction. Microglial infiltration is an important mediator in MSA. The nucleotide-binding domain, leucine-rich repeats-containing family, pyrin domain-containing-3 (NLRP3) inflammasome complex, comprising NLRP3, apoptotic speck protein containing a caspase recruitment domain (ASC), and cysteine aspartic acid protease 1 (Caspase 1), regulates microglial inflammation in several neurodegenerative diseases...
November 1, 2018: Journal of Neuropathology and Experimental Neurology
Jia Jia, Jian Cheng, Cheng Wang, Xuechu Zhen
A large body of evidence indicates that sigma-1 receptors (Sig-1R) are important drug targets for a number of neuropsychiatric disorders. Sig-1Rs are enriched in central nervous system (CNS). In addition to neurons, both cerebral microglia and astrocytes express Sig-1Rs. Activation of Sig-1Rs is known to elicit potent neuroprotective effects and promote neuronal survival via multiple mechanisms, including promoting mitochondrial functions, decreasing oxidative stress and regulating neuroimmnological functions...
2018: Frontiers in Cellular Neuroscience
Ashley Sterpka, Xuanmao Chen
Primary cilia are tiny microtubule-based signaling devices that regulate a variety of physiological functions, including metabolism and cell division. Defects in primary cilia lead to a myriad of diseases in humans such as obesity and cancers. In the mature brain, both neurons and astrocytes contain a single primary cilium. Although neuronal primary cilia are not directly involved in synaptic communication, their pathophysiological impacts on obesity and mental disorders are well recognized. In contrast, research on astrocytic primary cilia lags far behind...
October 4, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Brian V Lananna, Collin J Nadarajah, Mariko Izumo, Michelle R Cedeño, David D Xiong, Julie Dimitry, Chak Foon Tso, Celia A McKee, Percy Griffin, Patrick W Sheehan, Jeffery A Haspel, Ben A Barres, Shane A Liddelow, Joseph S Takahashi, Ilia N Karatsoreos, Erik S Musiek
Circadian clock dysfunction is a common symptom of aging and neurodegenerative diseases, though its impact on brain health is poorly understood. Astrocyte activation occurs in response to diverse insults and plays a critical role in brain health and disease. We report that the core circadian clock protein BMAL1 regulates astrogliosis in a synergistic manner via a cell-autonomous mechanism and a lesser non-cell-autonomous signal from neurons. Astrocyte-specific Bmal1 deletion induces astrocyte activation and inflammatory gene expression in vitro and in vivo, mediated in part by suppression of glutathione-S-transferase signaling...
October 2, 2018: Cell Reports
Matthew Neal, Jie Luo, Dilshan S Harischandra, Richard Gordon, Souvarish Sarkar, Huajun Jin, Vellareddy Anantharam, Laurent Désaubry, Anumantha Kanthasamy, Arthi Kanthasamy
Astrocyte reactivity is disease- and stimulus-dependent, adopting either a proinflammatory A1 phenotype or a protective, anti-inflammatory A2 phenotype. Recently, we demonstrated, using cell culture, animal models and human brain samples, that dopaminergic neurons produce and secrete higher levels of the chemokine-like signaling protein Prokineticin-2 (PK2) as a compensatory protective response against neurotoxic stress. As astrocytes express a high level of PK2 receptors, herein, we systematically characterize the role of PK2 in astrocyte structural and functional properties...
September 12, 2018: Glia
Shunya Yokota, Yui Kobatake, Yasuhiro Noda, Kohei Nakata, Osamu Yamato, Hideaki Hara, Hiroki Sakai, Hidetaka Nishida, Sadatohi Maeda, Hiroaki Kamishina
Canine degenerative myelopathy (DM) is an adult-onset progressive and fatal neurodegenerative disorder. Superoxide dismutase 1 (SOD1) mutations have been reported in affected dogs and immunohistochemical analyses revealed the accumulation of mutant SOD1 (E40K) in spinal neurons and astrocytes. Therefore, this disease is regarded as a unique spontaneous large-animal model of SOD1-mediated amyotrophic lateral sclerosis (ALS) in humans. Recent studies reported that endoplasmic reticulum (ER) stress is a key pathomechanism underlying motor neuron death in ALS...
September 29, 2018: Neuroscience Letters
Yujeong Lee, Jung-Hyun Cho, Seulah Lee, Wonjong Lee, Seung-Cheol Chang, Hae Young Chung, Hyung Ryong Moon, Jaewon Lee
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and are considered promising therapeutic targets in several neurodegenerative diseases. A number of PPAR agonists have been shown to have neuroprotective properties in the presence of oxidative stress, neuroinflammatory response, and apoptosis in various neurodegenerative disease. MHY908 is a novel PPAR α/γ dual agonist, which has been shown to suppress inflammatory response and attenuate insulin resistance in aged rats and db/db mice...
September 28, 2018: Brain Research
Feng Zhang, Ji-Guo Zhang, Wei Yang, Pu Xu, Yu-Liang Xiao, Han-Ting Zhang
6-Gingerol, the major component of gingerols extracted from Zingiber officinale, has been shown to exhibit anti-inflammatory and antioxidant bioactivities. Since neuroinflammation plays an important role in neurodegenerative diseases, such as Alzheimer's disease (AD), and astrocytes have been considered important in the process of neurodegeneration, it was of interest to know whether 6-gingerol reduced astrocytes activation or even attenuated cognitive impairment. Here we examined the neuroprotective effects of 6-gingerol in lipopolysaccharide (LPS)-induced disorder models both in vitro and in vivo...
November 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Aran Groves, Yasuyuki Kihara, Deepa Jonnalagadda, Richard Rivera, Grace Kennedy, Mark Mayford, Jerold Chun
Astrocytes have prominent roles in central nervous system (CNS) function and disease, with subpopulations defined primarily by morphologies and molecular markers often determined in cell culture. Here, we identify an in vivo astrocyte subpopulation termed immediate-early astrocytes ( ieAstrocytes ) that is defined by functional c-Fos activation during CNS disease development. An unbiased screen for CNS cells showing c-Fos activation during experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis (MS), was developed by using inducible, TetTag c-Fos reporter mice that label activated cells with a temporally stable, nuclear green fluorescent protein (GFP)...
September 2018: ENeuro
Jesse Slone, Yanyan Peng, Adam Chamberlin, Belinda Harris, Julie Kaylor, Marie T McDonald, Monica Lemmon, Mays Antonine El-Dairi, Dmitry Tchapyjnikov, Laura A Gonzalez-Krellwitz, Elizabeth A Sellars, Allyn McConkie-Rosell, Laura G Reinholdt, Taosheng Huang
Mitochondrial dysfunction lies behind many neurodegenerative disorders, owing largely to the intense energy requirements of most neurons. Such mitochondrial dysfunction may work through a variety of mechanisms, from direct disruption of the electron transport chain to abnormal mitochondrial biogenesis. Recently, we have identified biallelic mutations in the mitochondrial flavoprotein "ferredoxin reductase" (FDXR) gene as a novel cause of mitochondriopathy, peripheral neuropathy, and optic atrophy...
September 25, 2018: Journal of Human Genetics
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