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https://www.readbyqxmd.com/read/29352444/activation-of-the-anti-aging-and-cognition-enhancing-gene-klotho-by-crispr-dcas9-transcriptional-effector-complex
#1
Ci-Di Chen, Ella Zeldich, Yuexuan Li, Andrea Yuste, Carmela R Abraham
Multiple lines of evidence show that the anti-aging and cognition-enhancing protein Klotho fosters neuronal survival, increases the anti-oxidative stress defense, and promotes remyelination of demyelinated axons. Thus, upregulation of the Klotho gene can potentially alleviate the symptoms and/or prevent the progression of age-associated neurodegenerative diseases such as Alzheimer's disease and demyelinating diseases such as multiple sclerosis. Here we used a CRISPR-dCas9 complex to investigate single-guide RNA (sgRNA) targeting the Klotho promoter region for efficient transcriptional activation of the Klotho gene...
January 19, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29352424/cannabinoid-cb1-and-cb2%C3%A2-receptors-and-monoacylglycerol-lipase-gene-expression-alterations-in-the-basal-ganglia-of-patients-with-parkinson-s-disease
#2
Francisco Navarrete, M Salud García-Gutiérrez, Auxiliadora Aracil-Fernández, José L Lanciego, Jorge Manzanares
Previous studies suggest that the endocannabinoid system plays an important role in the neuropathological basis of Parkinson's disease (PD). This study was designed to detect potential alterations in the cannabinoid receptors CB1 (CB1r) and CB2 (A isoform, CB2Ar), and in monoacylglycerol lipase (MAGL) gene expression in the substantia nigra (SN) and putamen (PUT) of patients with PD. Immunohistochemical studies were performed to identify precise CB2r cellular localization in the SN of control and PD patients...
January 19, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29349661/pkm2-is-involved-in-neuropathic-pain-by-regulating-erk-and-stat3-activation-in-rat-spinal-cord
#3
Binbin Wang, Siyuan Liu, Bingbing Fan, Xingguo Xu, Yonglin Chen, Rongxiang Lu, Zhongling Xu, Xiaojuan Liu
BACKGROUND: Pyruvate kinase isozymes M2 (PKM2), as a member of pyruvate kinase family, plays a role of glycolytic enzyme in glucose metabolism. It also functions as protein kinase in cell proliferation, signaling, immunity, and gene transcription. In this study, the role of PKM2 in neuropathic pain induced by chronic constriction injury (CCI) was investigated. METHODS: Rats were randomly grouped to establish CCI models. PKM2, extracellular regulated protein kinases (EKR), p-ERK, signal transducers and activators of transcription (STAT3), p-STAT3, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and p-PI3K/AKT proteins expression in spinal cord was examined by Western blot analysis...
January 18, 2018: Journal of Headache and Pain
https://www.readbyqxmd.com/read/29346650/persistence-of-zika-virus-after-birth-clinical-virological-neuroimaging-and-neuropathological-documentation-in-a-5-month-infant-with-congenital-zika-syndrome
#4
Leila Chimelli, Sheila Moura Pone, Elyzabeth Avvad-Portari, Zilton Farias Meira Vasconcelos, Andrea Araújo Zin, Daniela Prado Cunha, Nathalia Raposo Thompson, Maria Elisabeth Lopes Moreira, Clayton A Wiley, Marcos Vinicius da Silva Pone
During the Zika epidemic in Brazil, a baby was born at term with microcephaly and arthrogryposis. The mother had Zika symptoms at 10 weeks of gestation. At 17 weeks, ultrasound showed cerebral malformation and ventriculomegaly. At 24 weeks, the amniotic fluid contained ZIKV RNA and at birth, placenta and maternal blood were also positive using RT-qPCR. At birth the baby urine contained ZIKV RNA, whereas CSF at birth and urine at 17 days did not. Seizures started at 6 days. EEG was abnormal and CT scan showed cerebral atrophy, calcifications, lissencephaly, ventriculomegaly, and cerebellar hypoplasia...
January 13, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29344929/pla2g6-deficiency-in-zebrafish-leads-to-dopaminergic-cell-death-axonal-degeneration-increased-%C3%AE-synuclein-expression-and-defects-in-brain-functions-and-pathways
#5
Elena Sánchez, Luis J Azcona, Coro Paisán-Ruiz
This study aimed to gain insights into the pathophysiology underlying PLA2G6-associated neurodegeneration that is implicated in three different neurological disorders, suggesting that other, unknown genetic or environmental factors might contribute to its wide phenotypic expression. To accomplish this, we downregulated the function of pla2g6 in the zebrafish nervous system, performed parkinsonism-related phenotypic characterization, and determined the effects of gene regulation upon the loss of pla2g6 function by using RNA sequencing and downstream analyses...
January 17, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29344870/cell-specific-rna-quantification-in-human-sn-da-neurons-from-heterogeneous-post-mortem-midbrain-samples-by-uv-laser-microdissection-and-rt-qpcr
#6
Johanna Duda, Michael Fauler, Jan Gründemann, Birgit Liss
Cell specificity of gene expression analysis is from particular relevance when the abundance of target cells is not homogeneous in the compared tissue samples, like it is the case, e.g., when comparing brain tissues from controls and in neurodegenerative disease states. While single-cell gene expression profiling is already a methodological challenge per se, it becomes even more prone to artifacts when analyzing individual cells from human post-mortem samples. Not only because human samples can never be matched as precisely as those from animal models, but also, because the RNA-quality that can be obtained from human samples usually displays a high range of variability...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29344864/laser-capture-microdissection-in-traumatic-brain-injury-research-obtaining-hippocampal-subregions-and-pools-of-injured-neurons-for-genomic-analyses
#7
Deborah R Boone, Harris A Weisz, Stacy L Sell, Helen L Hellmich
The methods presented here are based on our laboratory's 15 years of experience using laser capture microdissection to obtain samples for the study of gene expression after traumatic brain injury (TBI) using a well-established rat model of experimental TBI. Here, we describe how to use the ArcturusXT laser capture microdissection system to capture swaths of specific regions of the rat hippocampus as well as specific neuronal populations defined by Fluoro-Jade C staining. Staining with Fluoro-Jade C identifies a neuron that is in the process of degeneration...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29344862/cell-type-specific-laser-capture-microdissection-for-gene-expression-profiling-in-the-human-brain
#8
Sarah A Mauney, Tsung-Ung W Woo, Kai C Sonntag
Cell type-specific laser microdissection technologies in combination with molecular techniques to determine gene expression profiles have become powerful tools to gain insight into the neurobiological basis of neural circuit disturbances in various neurologic or psychiatric diseases. To identify specific cell populations in human postmortem brain tissue, one can use the inherent properties of the cells, such as pigmentation and morphology or their structural composition through immunohistochemistry (IHC). Here, we describe the isolation of homogeneous neurons and oligodendrocytes and the extraction of high-quality RNA from these cells in human postmortem brain using a combination of rapid IHC, Nissl staining, or simple morphology with Laser Capture Microdissection (LCM), or Laser Microdissection (LMD)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29343640/single-cell-transcriptomics-of-the-developing-lateral-geniculate-nucleus-reveals-insights-into-circuit-assembly-and-refinement
#9
Brian T Kalish, Lucas Cheadle, Sinisa Hrvatin, M Aurel Nagy, Samuel Rivera, Megan Crow, Jesse Gillis, Rory Kirchner, Michael E Greenberg
Coordinated changes in gene expression underlie the early patterning and cell-type specification of the central nervous system. However, much less is known about how such changes contribute to later stages of circuit assembly and refinement. In this study, we employ single-cell RNA sequencing to develop a detailed, whole-transcriptome resource of gene expression across four time points in the developing dorsal lateral geniculate nucleus (LGN), a visual structure in the brain that undergoes a well-characterized program of postnatal circuit development...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339826/using-intracellular-markers-to-identify-a-novel-set-of-surface-markers-for-live-cell-purification-from-a-heterogeneous-hipsc-culture
#10
Elizabeth J Paik, Alison L O'Neil, Shi-Yan Ng, Chicheng Sun, Lee L Rubin
Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can provide sources for midbrain dopaminergic (mDA) neural progenitors (NPCs) for cell therapy to treat Parkinson's disease (PD) patients. However, the well-known line-to-cell line variability in the differentiation capacity of individual cell lines needs to be improved for the success of this therapy. To address this issue, we sought to identify mDA NPC specific cell surface markers for fluorescence activated cell sorting (FACS). Through RNA isolation after sorting for NPCs based on staining for cell-specific transcription factors followed by microarray, we identified two positive cell surface markers (CORIN and CD166) and one negative cell surface marker (CXCR4) for mDA NPC sorting...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339018/nicotine-alleviates-chronic-stress-induced-anxiety-and-depressive-like-behavior-and-hippocampal-neuropathology-via-regulating-autophagy-signaling
#11
Xi Xiao, Xueliang Shang, Baohui Zhai, Hui Zhang, Tao Zhang
Recently, we reported that chronic nicotine significantly improved chronic stress-induced impairments of cognition and the hippocampal synaptic plasticity in mice, however, the underlying mechanism still needs to be explored. In the present study, 32 male C57BL/6 mice were divided into four groups: control (CON), stress (CUS), stress with chronic nicotine administration (CUS + Nic) and chronic nicotine administration (Nic). The anxiety-like behavior and neuropathological alteration of DG neurons were examined...
January 12, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29337236/maintenance-of-the-innate-seizure-threshold-by-cyclooxygenase-2-is-not-influenced-by-the-translational-silencer-t-cell-intracellular-antigen-1
#12
Yifan Gong, James A Hewett
Activity of neuronal cyclooxygenase-2 (COX-2), a primary source of PG synthesis in the normal brain, is enhanced by excitatory neurotransmission and this is thought to be involved in seizure suppression. Results herein showing that the incidence of pentylenetetrazole (PTZ)-induced convulsions is suppressed in transgenic mice overexpressing COX-2 in neurons supports this notion. T-cell intracellular antigen-1 (TIA-1) is an mRNA binding protein that is known to bind to COX-2 mRNA and repress its translation in non-neuronal cell types...
January 11, 2018: Neuroscience
https://www.readbyqxmd.com/read/29337114/pathological-endogenous-%C3%AE-synuclein-accumulation-in-oligodendrocyte-precursor-cells-potentially-induces-inclusions-in-multiple-system-atrophy
#13
Seiji Kaji, Takakuni Maki, Hisanori Kinoshita, Norihito Uemura, Takashi Ayaki, Yasuhiro Kawamoto, Takahiro Furuta, Makoto Urushitani, Masato Hasegawa, Yusuke Kinoshita, Yuichi Ono, Xiaobo Mao, Tran H Quach, Kazuhiro Iwai, Valina L Dawson, Ted M Dawson, Ryosuke Takahashi
Glial cytoplasmic inclusions (GCIs), commonly observed as α-synuclein (α-syn)-positive aggregates within oligodendrocytes, are the pathological hallmark of multiple system atrophy. The origin of α-syn in GCIs is uncertain; there is little evidence of endogenous α-syn expression in oligodendrocyte lineage cells, oligodendrocyte precursor cells (OPCs), and mature oligodendrocytes (OLGs). Here, based on in vitro analysis using primary rat cell cultures, we elucidated that preformed fibrils (PFFs) generated from recombinant human α-syn trigger multimerization and an upsurge of endogenous α-syn in OPCs, which is attributable to insufficient autophagic proteolysis...
December 27, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29335794/effect-of-a-calcitonin-gene-related-peptide-binding-l-rna-aptamer-on-neuronal-activity-in-the-rat-spinal-trigeminal-nucleus
#14
Michael J M Fischer, Jakob Schmidt, Stanislav Koulchitsky, Sven Klussmann, Axel Vater, Karl Messlinger
BACKGROUND: Calcitonin gene-related peptide (CGRP) plays a major role in the pathogenesis of migraine and other primary headaches. Spinal trigeminal neurons integrate nociceptive afferent input from trigeminal tissues including intracranial afferents, and their activity is thought to reflect facial pain and headache in man. CGRP receptor inhibitors and anti-CGRP antibodies have been demonstrated to be therapeutically effective in migraine. In parallel, CGRP receptor inhibition has been shown to lower spinal trigeminal neuron activity in animal models of meningeal nociception...
January 15, 2018: Journal of Headache and Pain
https://www.readbyqxmd.com/read/29335608/n6-methyladenosine-rna-modification-regulates-embryonic-neural-stem-cell-self-renewal-through-histone-modifications
#15
Yang Wang, Yue Li, Minghui Yue, Jun Wang, Sandeep Kumar, Robert J Wechsler-Reya, Zhaolei Zhang, Yuya Ogawa, Manolis Kellis, Gregg Duester, Jing Crystal Zhao
Internal N6-methyladenosine (m6A) modification is widespread in messenger RNAs (mRNAs) and is catalyzed by heterodimers of methyltransferase-like protein 3 (Mettl3) and Mettl14. To understand the role of m6A in development, we deleted Mettl14 in embryonic neural stem cells (NSCs) in a mouse model. Phenotypically, NSCs lacking Mettl14 displayed markedly decreased proliferation and premature differentiation, suggesting that m6A modification enhances NSC self-renewal. Decreases in the NSC pool led to a decreased number of late-born neurons during cortical neurogenesis...
January 15, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29335507/highly-conserved-molecular-pathways-including-wnt-signaling-promote-functional-recovery-from-spinal-cord-injury-in-lampreys
#16
Paige E Herman, Angelos Papatheodorou, Stephanie A Bryant, Courtney K M Waterbury, Joseph R Herdy, Anthony A Arcese, Joseph D Buxbaum, Jeramiah J Smith, Jennifer R Morgan, Ona Bloom
In mammals, spinal cord injury (SCI) leads to dramatic losses in neurons and synaptic connections, and consequently function. Unlike mammals, lampreys are vertebrates that undergo spontaneous regeneration and achieve functional recovery after SCI. Therefore our goal was to determine the complete transcriptional responses that occur after SCI in lampreys and to identify deeply conserved pathways that promote regeneration. We performed RNA-Seq on lamprey spinal cord and brain throughout the course of functional recovery...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29331684/reprogramming-neurodegeneration-in-the-big-data-era
#17
REVIEW
Lujia Zhou, Patrik Verstreken
Recent genome-wide association studies (GWAS) have identified numerous genetic risk variants for late-onset Alzheimer's disease (AD) and Parkinson's disease (PD). However, deciphering the functional consequences of GWAS data is challenging due to a lack of reliable model systems to study the genetic variants that are often of low penetrance and non-coding identities. Pluripotent stem cell (PSC) technologies offer unprecedented opportunities for molecular phenotyping of GWAS variants in human neurons and microglia...
January 10, 2018: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29328916/the-neuronal-gene-arc-encodes-a-repurposed-retrotransposon-gag-protein-that-mediates-intercellular-rna-transfer
#18
Elissa D Pastuzyn, Cameron E Day, Rachel B Kearns, Madeleine Kyrke-Smith, Andrew V Taibi, John McCormick, Nathan Yoder, David M Belnap, Simon Erlendsson, Dustin R Morado, John A G Briggs, Cédric Feschotte, Jason D Shepherd
The neuronal gene Arc is essential for long-lasting information storage in the mammalian brain, mediates various forms of synaptic plasticity, and has been implicated in neurodevelopmental disorders. However, little is known about Arc's molecular function and evolutionary origins. Here, we show that Arc self-assembles into virus-like capsids that encapsulate RNA. Endogenous Arc protein is released from neurons in extracellular vesicles that mediate the transfer of Arc mRNA into new target cells, where it can undergo activity-dependent translation...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29328915/retrovirus-like-gag-protein-arc1-binds-rna-and-traffics-across-synaptic-boutons
#19
James Ashley, Benjamin Cordy, Diandra Lucia, Lee G Fradkin, Vivian Budnik, Travis Thomson
Arc/Arg3.1 is required for synaptic plasticity and cognition, and mutations in this gene are linked to autism and schizophrenia. Arc bears a domain resembling retroviral/retrotransposon Gag-like proteins, which multimerize into a capsid that packages viral RNA. The significance of such a domain in a plasticity molecule is uncertain. Here, we report that the Drosophila Arc1 protein forms capsid-like structures that bind darc1 mRNA in neurons and is loaded into extracellular vesicles that are transferred from motorneurons to muscles...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29328494/pterostilbene-inhibits-reactive-oxygen-species-production-and-apoptosis-in-primary-spinal-cord-neurons-by-activating-autophagy-via-the-mechanistic-target-of-rapamycin-signaling-pathway
#20
Jing-Lan He, Xiao-Hui Dong, Zong-Hu Li, Xiao-Ying Wang, Zhi-An Fu, Na Shen
Autophagy is an important self-adaptive mechanism that is involved in inhibiting reactive oxygen species (ROS) in spinal cord neurons. Pterostilbene, a natural plant extract, has been demonstrated to possess antioxidant effects; however, it has not yet been investigated whether pterostilbene could activate autophagy and protect spinal cord neurons from oxidative stress. In the present study, primary spinal cord neurons of Sprague Dawley rats were cultured. Cell counting kit‑8 analysis was used to detect cytotoxicity of pterostilbene...
January 9, 2018: Molecular Medicine Reports
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