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https://www.readbyqxmd.com/read/29786967/developmental-chromatin-restriction-of-pro-growth-gene-networks-acts-as-an-epigenetic-barrier-to-axon-regeneration-in-cortical-neurons
#1
Ishwariya Venkatesh, Vatsal Mehra, Zimei Wang, Ben Califf, Murray G Blackmore
Axon regeneration in the central nervous system is prevented in part by a developmental decline in the intrinsic regenerative ability of maturing neurons. This loss of axon growth ability likely reflects widespread changes in gene expression, but the mechanisms that drive this shift remain unclear. Chromatin accessibility has emerged as a key regulatory mechanism in other cellular contexts, raising the possibility that chromatin structure may contribute to the age-dependent loss of regenerative potential. Here we establish an integrated bioinformatic pipeline that combines analysis of developmentally dynamic gene networks with transcription factor regulation and genome-wide maps of chromatin accessibility...
May 22, 2018: Developmental Neurobiology
https://www.readbyqxmd.com/read/29786910/agathisflavone-isolated-from-anacardium-occidentale-suppresses-sirt1-mediated-neuroinflammation-in-bv2-microglia-and-neurotoxicity-in-appswe-transfected-sh-sy5y-cells
#2
Ravikanth Velagapudi, Olusiji O Ajileye, Uchechukwu Okorji, Priya Jain, Mutalib A Aderogba, Olumayokun A Olajide
Agathisflavone is a bioactive compound in Anacardium occidentale. In this study, we investigated inhibition neuroinflammation in BV2 microglia by agathisflavone. Neuroprotective activity of the compound was investigated in differentiated SH-SY5Y cells. Experiments in lipopolysaccharide (LPS)-activated BV2 microglia showed that pretreatment with agathisflavone (5-20 μM) produced significant reduction in the release of tumour necrosis factor-α, interleukin-6, interleukin-1β, NO, and PGE2 from the cells. Immunoblotting experiments also revealed that agathisflavone reduced levels of iNOS and COX-2 protein...
May 22, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29786763/mir-124-promotes-proliferation-and-neural-differentiation-of-neural-stem-cells-through-targeting-dact1-and-activating-wnt-%C3%AE-catenin-pathways
#3
Shujie Jiao, Yaling Liu, Yaobing Yao, Junfang Teng
Neural stem cells (NSCs) are multipotent and undifferentiated cells with the potential to differentiate into neuronal lineages and gliocytes. NSCs have the ability to generate and regenerate the brain, indicating the possibility of cell-based therapies for neurological disorders. miR-124 has been demonstrated as a modulator in the survival, expansion, and differentiation of NSCs. However, the underlying molecular mechanisms of miR-124 in NSC development are still far from being understood. The expressions of miR-124, dishevelled binding antagonist of beta-catenin 1 (DACT1), ki-67, Nestin, β-tubulin III, glial fibrillary acidic protein (GFAP), β-catenin, cyclinD1, and glycogen synthase kinase-3β (GSK-3β) were examined by qRT-PCR or western blot...
May 21, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29786756/backbone-nmr-assignments-of-hypf-n-under-conditions-generating-toxic-and-non-toxic-oligomers
#4
Jayneil R Patel, Yingqi Xu, Claudia Capitini, Fabrizio Chiti, Alfonso De Simone
The HypF protein is involved in the maturation and regulation of hydrogenases. The N-terminal domain of HypF (HypF-N) has served as a key model system to study the pathways of protein amyloid formation and the nature of the toxicity of pre-fibrilar protein oligomers. This domain can aggregate into two forms of oligomers having significantly different toxic effects when added to neuronal cultures. Here, NMR assignments of HypF-N backbone resonances are presented in its native state and under the conditions favouring the formation of toxic and non-toxic oligomers...
May 21, 2018: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/29786697/imaging-glutathione-depletion-in-the-rat-brain-using-ascorbate-derived-hyperpolarized-mr-and-pet-probes
#5
Hecong Qin, Valerie N Carroll, Renuka Sriram, Javier E Villanueva-Meyer, Cornelius von Morze, Zhen Jane Wang, Christopher A Mutch, Kayvan R Keshari, Robert R Flavell, John Kurhanewicz, David M Wilson
Oxidative stress is a critical feature of several common neurologic disorders. The brain is well adapted to neutralize oxidative injury by maintaining a high steady-state concentration of small-molecule intracellular antioxidants including glutathione in astrocytes and ascorbic acid in neurons. Ascorbate-derived imaging probes for hyperpolarized 13 C magnetic resonance spectroscopy and positron emission tomography have been used to study redox changes (antioxidant depletion and reactive oxygen species accumulation) in vivo...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29786685/regulation-of-chromatin-states-and-gene-expression-during-hsn-neuronal-maturation-is-mediated-by-eor-1-plzf-mau-2-cohesin-loader-and-swi-snf-complex
#6
Yoichi Shinkai, Masahiro Kuramochi, Motomichi Doi
Newborn neurons mature by distinct and sequential steps through the timely induction of specific gene expression programs in concert with epigenetic changes. However, it has been difficult to investigate the relationship between gene expression and epigenetic changes at a single-cell resolution during neuronal maturation. In this study, we investigated the maturation of hermaphrodite-specific neurons (HSNs) in C. elegans, which provided the link between chromatin dynamics, gene expression, and the degree of neuronal maturation at a single-cell resolution...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29786658/melatonin-as-a-therapy-for-traumatic-brain-injury-a-review-of-published-evidence
#7
REVIEW
Nicole Osier, Emily McGreevy, Lan Pham, Ava Puccio, Dianxu Ren, Yvette P Conley, Sheila Alexander, C Edward Dixon
Melatonin (MEL) is a hormone that is produced in the brain and is known to bind to MEL-specific receptors on neuronal membranes in several brain regions. MEL's documented neuroprotective properties, low toxicity, and ability to cross the blood-brain-barrier have led to its evaluation for patients with traumatic brain injury (TBI), a condition for which there are currently no Food and Drug Administration (FDA)-approved therapies. The purpose of this manuscript is to summarize the evidence surrounding the use of melatonin after TBI, as well as identify existing gaps and future directions...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786653/role-for-cystathionine-%C3%AE-lyase-cse-in-an-ethanol-e-induced-lesion-in-fetal-brain-gsh-homeostasis
#8
Dhyanesh Patel, Marylatha Rathinam, Courtney Jarvis, Lenin Mahimainathan, George Henderson, Madhusudhanan Narasimhan
Earlier, we reported that gestational ethanol (E) can dysregulate neuron glutathione (GSH) homeostasis partially via impairing the EAAC1-mediated inward transport of Cysteine (Cys) and this can affect fetal brain development. In this study, we investigated if there is a role for the transulfuration pathway (TSP), a critical bio-synthetic point to supply Cys in E-induced dysregulation of GSH homeostasis. These studies utilized an in utero E binge model where the pregnant Sprague⁻Dawley (SD) rat dams received five doses of E at 3...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786645/skeletal-muscle-micrornas-as-key-players-in-the-pathogenesis-of-amyotrophic-lateral-sclerosis
#9
REVIEW
Lorena Di Pietro, Wanda Lattanzi, Camilla Bernardini
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, for which, to date, no effective treatment to ameliorate the clinical manifestations is available. The long-standing view of ALS as affecting only motor neurons has been challenged by the finding that the skeletal muscle plays an active role in the disease pathogenesis and can be a valuable target for therapeutic strategies. In recent years, non-coding RNAs, including microRNAs, have emerged as important molecules that play key roles in several cellular mechanisms involved in the pathogenic mechanisms underlying various human conditions...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786643/controlled-deactivation-cb1-receptor-ligands-as-a-novel-strategy-to-lower-intraocular-pressure
#10
Sally Miller, Shashank Kulkarni, Alex Ciesielski, Spyros P Nikas, Ken Mackie, Alexandros Makriyannis, Alex Straiker
Nearly half a century has passed since the demonstration that cannabis and its chief psychoactive component Δ⁸-THC lowers intraocular pressure (IOP). Elevated IOP remains the chief hallmark and therapeutic target for glaucoma, a condition that places millions at risk of blindness. It is likely that Δ⁸-THC exerts much of its IOP-lowering effects via the activation of CB1 cannabinoid receptors. However, the initial promise of CB1 as a target for treating glaucoma has not thus far translated into a credible therapeutic strategy...
May 22, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29786639/chemogenetic-enhancement-of-axon-regeneration-following-peripheral-nerve-injury-in-the-slick-a-mouse
#11
Poonam B Jaiswal, Olivia C Mistretta, Patricia J Ward, Arthur W English
The effects of chemogenetics on axon regeneration following peripheral nerve transection and repair were studied in mice expressing a Cre-dependent excitatory designer receptor exclusively activated by designer drugs (DREADD) and Cre-recombinase/yellow fluorescent protein (YFP) in a subset of motor and sensory neurons and cortical motoneurons (SLICK-A). Sciatic nerves were cut and repaired and mice were treated either once, at the time of injury, or five days per week for two weeks with clozapine N-oxide (CNO) (1 mg/kg, i...
May 22, 2018: Brain Sciences
https://www.readbyqxmd.com/read/29786594/-brain-microbleeds-definition-pathophysiology-and-the-consequences
#12
Marek Mazurek, Ewa Papuć, Konrad Rejdak
Brain microbleeds are defined as small, circular hypointense changes in T2-sequensec of brain MRI, well demarcated from the surrounding tissue. They represent the phagocytized products of blood distribution extravasated from pathologically altered vessels. The echo-T2-dependent gradient (GRE) and magnetic susceptibility testing (SWI) sequences are usually used to visualize them. The pathogenesis of microbleeds very complex but angiopathy associated with arterial hypertension and cerebral amyloid angiopathy play a special role...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29786554/a-human-ipsc-line-capable-of-differentiating-into-functional-macrophages-expressing-zsgreen-a-tool-for-the-study-and-in-vivo-tracking-of-therapeutic-cells
#13
Martha Lopez-Yrigoyen, Antonella Fidanza, Luca Cassetta, Richard A Axton, A Helen Taylor, Jose Meseguer-Ripolles, Anestis Tsakiridis, Valerie Wilson, David C Hay, Jeffrey W Pollard, Lesley M Forrester
We describe the production of a human induced pluripotent stem cell (iPSC) line, SFCi55-ZsGr, that has been engineered to express the fluorescent reporter gene, ZsGreen, in a constitutive manner. The CAG-driven ZsGreen expression cassette was inserted into the AAVS1 locus and a high level of expression was observed in undifferentiated iPSCs and in cell lineages derived from all three germ layers including haematopoietic cells, hepatocytes and neurons. We demonstrate efficient production of terminally differentiated macrophages from the SFCi55-ZsGreen iPSC line and show that they are indistinguishable from those generated from their parental SFCi55 iPSC line in terms of gene expression, cell surface marker expression and phagocytic activity...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786550/generation-of-defined-neural-populations-from-pluripotent-stem-cells
#14
REVIEW
Sarah F McComish, Maeve A Caldwell
Effective and efficient generation of human neural stem cells and subsequently functional neural populations from pluripotent stem cells has facilitated advancements in the study of human development and disease modelling. This review will discuss the established protocols for the generation of defined neural populations including regionalized neurons and astrocytes, oligodendrocytes and microglia. Early protocols were established in embryonic stem cells (ESC) but the discovery of induced pluripotent stem cells (iPSC) in 2006 provided a new platform for modelling human disorders of the central nervous system (CNS)...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786422/mechanisms-regulating-the-association-of-protein-phosphatase-1-with-spinophilin-and-neurabin
#15
Michael C Edler, Asma B Salek, Darryl S Watkins, Harjot Kaur, Cameron W Morris, Bryan K Yamamoto, Anthony J Baucum
Protein phosphorylation is a key mediator of signal transduction, allowing for dynamic regulation of substrate activity. Whereas protein kinases obtain substrate specificity by targeting specific amino acid sequences, serine/threonine phosphatase catalytic subunits are much more promiscuous in their ability to dephosphorylate substrates. To obtain substrate specificity, serine/threonine phosphatases utilize targeting proteins to regulate phosphatase subcellular localization and catalytic activity. Spinophilin and its homolog neurabin are two of the most abundant dendritic spine-localized protein phosphatase 1 (PP1) targeting proteins...
May 22, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29786167/neuroplasticity-in-stroke-recovery-the-role-of-microglia-in-engaging-and-modifying-synapses-and-networks
#16
REVIEW
Ioanna Sandvig, Ingrid Lovise Augestad, Asta Kristine Håberg, Axel Sandvig
Neuroplasticity after ischemic injury involves both spontaneous rewiring of neural networks and circuits as well as functional responses in neurogenic niches. These events involve complex interactions with activated microglia, which evolve in a dynamic manner over time. Although the exact mechanisms underlying these interactions remain poorly understood, increasing experimental evidence suggests a determining role of pro- and anti-inflammatory microglial activation profiles in shaping both synaptogenesis and neurogenesis...
May 22, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29786160/aberrant-learning-in-parkinson-s-disease-a-neurocomputational-study-on-bradykinesia
#17
Mauro Ursino, Chiara Baston
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive decline in motor functions, such as bradykinesia, caused by the pathological denervation of nigrostriatal dopaminergic neurons within the basal ganglia (BG). It is acknowledged that dopamine (DA) directly affects the modulatory role of BG towards the cortex. However, a growing body of literature is suggesting that DA induced aberrant synaptic plasticity could play a role in the core symptoms of PD, thus recalling for a "reconceptualization" of the pathophysiology...
May 22, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29786105/cannabinoid-win-55-212-2-mesylate-inhibits-tumor-necrosis-factor-%C3%AE-induced-expression-of-nitric-oxide-synthase-in-dorsal-root-ganglion-neurons
#18
Rong Tan, Lijun Cao
Tumor necrosis factor-α (TNF-α) is an established pain modulator in the peripheral nervous system. Elevated levels of TNF-α in dorsal root ganglion (DRG) neurons reportedly is critical for neuropathic pain processing. It has been shown that the production of nitric oxide, a key player in the development and maintenance of nociception, depends on the expression of nitric oxide synthases (NOSs) and their activities. Accumulating evidence also supports an important role of cannabinoids in modulating neuropathic pain...
May 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786093/author-correction-high-speed-volumetric-imaging-of-neuronal-activity-in-freely-moving-rodents
#19
Oliver Skocek, Tobias Nöbauer, Lukas Weilguny, Francisca Martínez Traub, Chuying Naomi Xia, Maxim I Molodtsov, Abhinav Grama, Masahito Yamagata, Daniel Aharoni, David D Cox, Peyman Golshani, Alipasha Vaziri
In the version of this Brief Communication originally published online, ref. 21 included details for a conference paper (Pegard, N. C. et al. Paper presented at Novel Techniques in Microscopy: Optics in the Life Sciences, Vancouver, BC, Canada, 12-15 April 2015). The correct reference is the following: Pégard, N. C. et al. Optica 3, 517-524 (2016). This error has been corrected in the print, HTML and PDF versions of the paper.
May 21, 2018: Nature Methods
https://www.readbyqxmd.com/read/29786085/chronic-crh-depletion-from-gabaergic-long-range-projection-neurons-in-the-extended-amygdala-reduces-dopamine-release-and-increases-anxiety
#20
Nina Dedic, Claudia Kühne, Mira Jakovcevski, Jakob Hartmann, Andreas J Genewsky, Karina S Gomes, Elmira Anderzhanova, Max L Pöhlmann, Simon Chang, Adam Kolarz, Annette M Vogl, Julien Dine, Michael W Metzger, Bianca Schmid, Rafael C Almada, Kerry J Ressler, Carsten T Wotjak, Valery Grinevich, Alon Chen, Mathias V Schmidt, Wolfgang Wurst, Damian Refojo, Jan M Deussing
The interplay between corticotropin-releasing hormone (CRH) and the dopaminergic system has predominantly been studied in addiction and reward, while CRH-dopamine interactions in anxiety are scarcely understood. We describe a new population of CRH-expressing, GABAergic, long-range-projecting neurons in the extended amygdala that innervate the ventral tegmental area and alter anxiety following chronic CRH depletion. These neurons are part of a distinct CRH circuit that acts anxiolytically by positively modulating dopamine release...
May 21, 2018: Nature Neuroscience
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