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Neurodegeneration

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https://www.readbyqxmd.com/read/28449038/real-time-imaging-of-single-neuronal-cell-apoptosis-in-patients-with-glaucoma
#1
Maria F Cordeiro, Eduardo M Normando, M Jorge Cardoso, Serge Miodragovic, Seham Jeylani, Benjamin M Davis, Li Guo, Sebastien Ourselin, Roger A'Hern, Philip A Bloom
Retinal cell apoptosis occurs in many ocular neurodegenerative conditions including glaucoma-the major cause of irreversible blindness worldwide. Using a new imaging technique that we have called DARC (detection of apoptosing retinal cells), which until now has only been demonstrated in animal models, we assessed if annexin 5 labelled with fluorescent dye DY-776 (ANX776) could be used safely in humans to identify retinal cell apoptosis. Eight patients with glaucomatous neurodegeneration and evidence of progressive disease, and eight healthy subjects were randomly assigned to intravenous ANX776 doses of 0...
April 26, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28448671/disrupted-eye-movements-in-preperimetric-primary-open-angle-glaucoma
#2
Raymond P Najjar, Sourabh Sharma, Morgane Drouet, Stephanie Leruez, Mani Baskaran, Monisha E Nongpiur, Tin Aung, Joanne Fielding, Owen White, Michael J Girard, Cédric Lamirel, Dan Milea
Purpose: Primary open-angle glaucoma (POAG) can be associated with abnormal ocular motor behavior, possibly as a compensatory strategy following visual field loss. The aim of this study was to explore the characteristics of saccadic eye movements in patients with early-stage POAG without any detectable glaucomatous visual field loss (i.e., preperimetric POAG). Methods: Binocular eye movements were explored in 16 patients with bilateral preperimetric POAG and 16 age-matched healthy controls in a cross-sectional, observational study...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28447995/rapid-and-refined-cd11b-magnetic-isolation-of-primary-microglia-with-enhanced-purity-and-versatility
#3
Souvarish Sarkar, Emir Malovic, Brandon Plante, Gary Zenitsky, Huajun Jin, Vellareddy Anantharam, Arthi Kanthasamy, Anumantha G Kanthasamy
Microglia are the primary responders to central nervous system insults; however, much remains unknown about their role in regulating neuroinflammation. Microglia are mesodermal cells that function similarly to macrophages in surveying inflammatory stress. The classical (M1-type) and alternative (M2-type) activations of macrophages have also been extended to microglia in an effort to better understand the underlying interplay these phenotypes have in neuroinflammatory conditions such as Parkinson's, Alzheimer's, and Huntington's Diseases...
April 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447589/neuroretinal-evaluation-using-optical-coherence-tomography-in-patients-affected-by-pituitary-tumors
#4
Yasar Altun, Ayse Sevgi Karadag, Seyho Cem Yucetas, Sadullah Saglam, A Z A Tak, Ilhan Cag, Yusuf Ehi
AIM: To investigate the thickness of the retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), inner plexiform layer (IPL), and choroid thickness (CT) in patients with pituitary tumours, microadenoma and macroadenoma, using spectral optical coherence tomography (OCT). METHODS: Thirty six patients who had micro and macroadenoma, and 34 healthy participants (control group) were included in the study. Spectral OCT was used to measure the RNFL, GCL, IPL, and CT values for all patients...
2017: Annali Italiani di Chirurgia
https://www.readbyqxmd.com/read/28446708/structural-and-functional-analysis-of-oceanobacillus-iheyensis-macrodomain-reveals-a-network-of-waters-involved-in-substrate-binding-and-catalysis
#5
Rubén Zapata-Pérez, Fernando Gil-Ortiz, Ana Belén Martínez-Moñino, Antonio Ginés García-Saura, Jordi Juanhuix, Álvaro Sánchez-Ferrer
Macrodomains are ubiquitous conserved domains that bind or transform ADP-ribose (ADPr) metabolites. In humans, they are involved in transcription, X-chromosome inactivation, neurodegeneration and modulating PARP1 signalling, making them potential targets for therapeutic agents. Unfortunately, some aspects related to the substrate binding and catalysis of MacroD-like macrodomains still remain unclear, since mutation of the proposed catalytic aspartate does not completely abolish enzyme activity. Here, we present a functional and structural characterization of a macrodomain from the extremely halotolerant and alkaliphilic bacterium Oceanobacillus iheyensis (OiMacroD), related to hMacroD1/hMacroD2, shedding light on substrate binding and catalysis...
April 2017: Open Biology
https://www.readbyqxmd.com/read/28446679/central-nervous-system-infection-with-borna-disease-virus-causes-kynurenine-pathway-dysregulation-and-neurotoxic-quinolinic-acid-production
#6
Simone Formisano, Mady Hornig, Kavitha Yaddanapudi, Mansi Vasishtha, Loren H Parsons, Thomas Briese, W Ian Lipkin, Brent L Williams
Central nervous system infection of neonatal and adult rats with Borna disease virus (BDV) results in neuronal destruction and behavioral abnormalities with differential immune-mediated involvement. Neuroactive metabolites generated from the kynurenine pathway of tryptophan degradation have been implicated in several human neurodegenerative disorders. Here we report that brain expression of key enzymes in the kynurenine pathway are significantly, but differentially, altered in neonatal and adult rats with BDV infection...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446179/glycam1-negatively-regulates-monocyte-entry-into-the-optic-nerve-head-and-contributes-to-radiation-based-protection-in-glaucoma
#7
Pete A Williams, Catherine E Braine, Nicole E Foxworth, Kelly E Cochran, Simon W M John
BACKGROUND: We previously reported a profound long-term neuroprotection subsequent to a single radiation-therapy in the DBA/2J mouse model of glaucoma. This neuroprotection prevents entry of monocyte-like immune cells into the optic nerve head during glaucoma. Gene expression studies in radiation-treated mice implicated Glycam1 in this protection. Glycam1 encodes a proteoglycan ligand for L-selectin and is an excellent candidate to modulate immune cell entry into the eye. Here, we experimentally test the hypothesis that radiation-induced over-expression of Glycam1 is a key component of the neuroprotection...
April 26, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28445733/nf-%C3%AE%C2%BAb-immunity-in-the-brain-determines-fly-lifespan-in-healthy-aging-and-age-related-neurodegeneration
#8
Ilias Kounatidis, Stanislava Chtarbanova, Yang Cao, Margaret Hayne, Dhruv Jayanth, Barry Ganetzky, Petros Ligoxygakis
During aging, innate immunity progresses to a chronically active state. However, what distinguishes those that "age well" from those developing age-related neurological conditions is unclear. We used Drosophila to explore the cost of immunity in the aging brain. We show that mutations in intracellular negative regulators of the IMD/NF-κB pathway predisposed flies to toxic levels of antimicrobial peptides, resulting in early locomotor defects, extensive neurodegeneration, and reduced lifespan. These phenotypes were rescued when immunity was suppressed in glia...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445716/trumping-neurodegeneration-targeting-common-pathways-regulated-by-autosomal-recessive-parkinson-s-disease-genes
#9
REVIEW
Laura Scott, Valina L Dawson, Ted M Dawson
Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the progressive loss of dopaminergic (DA) neurons. Most PD cases are sporadic; however, rare familial forms have been identified. Autosomal recessive PD (ARPD) results from mutations in Parkin, PINK1, DJ-1, and ATP13A2, while rare, atypical juvenile ARPD result from mutations in FBXO7, DNAJC6, SYNJ1, and PLA2G6. Studying these genes and their function has revealed mitochondrial quality control, protein degradation processes, and oxidative stress responses as common pathways underlying PD pathogenesis...
April 23, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28445458/neurodegeneration-role-of-repeats-in-protein-clearance
#10
Dale D O Martin, Michael R Hayden
No abstract text is available yet for this article.
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28444917/ultrastructural-comparison-of-the-drosophila-larval-and-adult-ventral-abdominal-neuromuscular-junction
#11
Nicole Wagner
Drosophila melanogaster has recently emerged as model system for studying synaptic transmission and plasticity during adulthood, aging and neurodegeneration. However, still little is known about the basic neuronal mechanisms of synaptic function in the adult fly. Per se, adult Drosophila neuromuscular junctions should be highly suited for studying these aspects as they allow for genetic manipulations in combination with ultrastructural and electrophysiological analyses. Although different neuromuscular junctions of the adult fly have been described during the last years, a direct ultrastructural comparison with their larval counterpart is lacking...
April 26, 2017: Journal of Morphology
https://www.readbyqxmd.com/read/28444734/highly-electronegative-low-density-lipoprotein-l5-evokes-microglial-activation-and-creates-a-neuroinflammatory-stress-via-toll-like-receptor-4-signaling
#12
Liang-En Yu, Chiou-Lian Lai, Ching-Tien Lee, Jiz-Yuh Wang
Atherogenic risk factors, such as hypercholesterolemia, are associated with increased risk of neurodegeneration, especially Alzheimer's dementia. Human plasma electronegative low-density lipoprotein [LDL(-)], especially L5, may serve as an important contributing factor. L5 promoting an inflammatory action in atherosclerosis has been extensively studied. However, the role of L5 in inducing neuroinflammation remains unknown. Here, we examined the impact of L5 on immune activation and cell viability in cultured BV-2 microglia...
April 26, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28444635/the-leukocentric-theory-of-neurological-disorder-a-manifesto
#13
Robert Fern
Approximately half of the human brain is composed of white matter (WM), a specialized tissue housing the axonal projection of neurons and their necessary supporting glial cells. Axons course long distances from their parent soma, have a delicate structure, large surface area and in many cases are dependent upon a uniquely close morphological arrangement with myelinating oligodendrocyte partners; all factors that may predispose them to injury and disease. WM damage is central to a range of well-characterized disorders including multiple sclerosis and spinal cord injury and is also makes a significant contribution to disorders often considered to be largely focused in gray matter; for example, in stroke where ~49% of injury by volume is located in WM...
April 25, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28444183/calcium-dysregulation-and-cdk5-atm-pathway-involved-in-a-mouse-model-of-fragile-x-associated-tremor-ataxia-syndrome
#14
Gaëlle Robin, José R López, Glenda M Espinal, Susan Hulsizer, Paul J Hagerman, Isaac N Pessah
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurological disorder that affects premutation carriers with 55-200 CGG-expansion repeats (preCGG) in FMR1, presenting with early alterations in neuronal network formation and function that precede neurodegeneration. Whether intranuclear inclusions containing DNA damage response (DDR) proteins, are causally linked to abnormal synaptic function, neuronal growth and survival are unknown. In a mouse that harbors a premutation CGG expansion (preCGG), cortical and hippocampal FMRP expression is moderately reduced from birth through adulthood, with greater FMRP reductions in the soma than in the neurite, despite several-fold elevation of Fmr1 mRNA levels...
April 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28442946/optogenetic-rescue-of-locomotor-dysfunction-and-dopaminergic-degeneration-caused-by-alpha-synuclein-and-eko-genes
#15
Cheng Qi, Scott Varga, Soo-Jin Oh, C Justin Lee, Daewoo Lee
α-Synuclein (α-Syn) is a small presynaptic protein and its mutant forms (e.g. A53T) are known to be directly associated with Parkinson's disease (PD). Pathophysiological mechanisms underlying α-Syn-mediated neurodegeneration in PD still remain to be explored. However, several studies strongly support that overexpression of mutant α-Syn causes reduced release of dopamine (DA) in the brain, and contributes to motor deficits in PD. Using a favorable genetic model Drosophila larva, we examined whether reduced DA release is enough to induce key PD symptoms (i...
April 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28442885/complement-c5a-receptor-knockout-has-diminished-light-induced-microglia-macrophage-retinal-migration
#16
Delu Song, Michael E Sulewski, Chenguang Wang, Jiantao Song, Rupak Bhuyan, Jacob Sterling, Esther Clark, Wen-Chao Song, Joshua L Dunaief
PURPOSE: The complement system is involved in the pathogenesis of age-related macular degeneration (AMD). Because activated microglia are also associated with AMD, we studied the relationship between complement anaphylatoxin receptors and microglial recruitment. METHODS: We assessed the effect of anaphylatoxin C3a receptor (C3aR) and C5a receptor (C5aR) knockout (KO) on light damage-induced migration of microglia/macrophages into the mouse outer retina via immunofluorescence and real-time quantitative PCR...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28442781/spreading-depolarization-remarkably-exacerbates-ischemia-induced-tissue-acidosis-in-the-young-and-aged-rat-brain
#17
Ákos Menyhárt, Dániel Zölei-Szénási, Tamás Puskás, Péter Makra, M Tóth Orsolya, Borbála É Szepes, Réka Tóth, Orsolya Ivánkovits-Kiss, Tihomir P Obrenovitch, Ferenc Bari, Eszter Farkas
Spreading depolarizations (SDs) occur spontaneously in the cerebral cortex of subarachnoid hemorrhage, stroke or traumatic brain injury patients. Accumulating evidence prove that SDs exacerbate focal ischemic injury by converting zones of the viable but non-functional ischemic penumbra to the core region beyond rescue. Yet the SD-related mechanisms to mediate neurodegeneration remain poorly understood. Here we show in the cerebral cortex of isoflurane-anesthetized, young and old laboratory rats, that SDs propagating under ischemic penumbra-like conditions decrease intra and- extracellular tissue pH transiently to levels, which have been recognized to cause tissue damage...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442607/n-methyl-d-aspartate-nmda-receptor-blockade-prevents-neuronal-death-induced-by-zika-virus-infection
#18
Vivian V Costa, Juliana L Del Sarto, Rebeca F Rocha, Flavia R Silva, Juliana G Doria, Isabella G Olmo, Rafael E Marques, Celso M Queiroz-Junior, Giselle Foureaux, Julia Maria S Araújo, Allysson Cramer, Ana Luíza C V Real, Lucas S Ribeiro, Silvia I Sardi, Anderson J Ferreira, Fabiana S Machado, Antônio C de Oliveira, Antônio L Teixeira, Helder I Nakaya, Danielle G Souza, Fabiola M Ribeiro, Mauro M Teixeira
Zika virus (ZIKV) infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated by N-methyl-d-aspartate receptor (NMDAR)-dependent neuronal excitoxicity. Here, we have exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by blocking NMDA overstimulation with memantine. Our results show that ZIKV actively replicates in primary neurons and that virus replication is directly associated with massive neuronal cell death. Interestingly, treatment with memantine or other NMDAR blockers, including dizocilpine (MK-801), agmatine sulfate, or ifenprodil, prevents neuronal death without interfering with the ability of ZIKV to replicate in these cells...
April 25, 2017: MBio
https://www.readbyqxmd.com/read/28442549/neuraminidases-3-and-4-regulate-neuronal-function-by-catabolizing-brain-gangliosides
#19
Xuefang Pan, Camila De Britto Pará De Aragão, Juan P Velasco-Martin, David A Priestman, Harry Y Wu, Kohta Takahashi, Kazunori Yamaguchi, Luisella Sturiale, Domenico Garozzo, Frances M Platt, Nathalie Lamarche-Vane, Carlos R Morales, Taeko Miyagi, Alexey V Pshezhetsky
Gangliosides (sialylated glycolipids) play an essential role in the CNS by regulating recognition and signaling in neurons. Metabolic blocks in processing and catabolism of gangliosides result in the development of severe neurologic disorders, including gangliosidoses manifesting with neurodegeneration and neuroinflammation. We demonstrate that 2 mammalian enzymes, neuraminidases 3 and 4, play important roles in catabolic processing of brain gangliosides by cleaving terminal sialic acid residues in their glycan chains...
April 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28442392/4-chlorodiazepam-is-neuroprotective-against-amyloid-beta-in-organotypic-hippocampal-cultures
#20
B D Arbo, J B Hoppe, K Rodrigues, L M Garcia-Segura, C G Salbego, M F Ribeiro
The translocator protein (TSPO) is an outer mitochondrial membrane protein involved in the transport of cholesterol into the mitochondria, which is the first step for the synthesis of steroid hormones, as well as in the regulation of mitochondrial permeability transition pore opening and apoptosis. Studies have shown that the activation of TSPO may promote neuroprotective actions in experimental models of neurodegeneration and brain injury. In a previous study, our group showed that 4'-chlorodiazepam (4'-CD), a TSPO ligand, was neuroprotective against amyloid-beta (Aβ) in SHSY-5Y neuroblastoma cells...
April 22, 2017: Journal of Steroid Biochemistry and Molecular Biology
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