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https://www.readbyqxmd.com/read/28100454/gene-therapy-targeting-oligodendrocytes-provides-therapeutic-benefit-in-a-leukodystrophy-model
#1
Elena Georgiou, Kyriaki Sidiropoulou, Jan Richter, Christos Papaneophytou, Irene Sargiannidou, Alexia Kagiava, Georg von Jonquieres, Christina Christodoulou, Matthias Klugmann, Kleopas A Kleopa
Pelizaeus-Merzbacher-like disease or hypomyelinating leukodystrophy-2 is an autosomal recessively inherited leukodystrophy with childhood onset resulting from mutations in the gene encoding the gap junction protein connexin 47 (Cx47, encoded by GJC2). Cx47 is expressed specifically in oligodendrocytes and is crucial for gap junctional communication throughout the central nervous system. Previous studies confirmed that a cell autonomous loss-of-function mechanism underlies hypomyelinating leukodystrophy-2 and that transgenic oligodendrocyte-specific expression of another connexin, Cx32 (GJB1), can restore gap junctions in oligodendrocytes to achieve correction of the pathology in a disease model...
January 18, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28096472/myosin-vi-facilitates-connexin-43-gap-junction-accretion
#2
Bennett Waxse, Prabuddha Sengupta, Geoffrey G Hesketh, Jennifer Lippincott-Schwartz, Folma Buss
In this study, we demonstrate myosin VI enrichment at Cx43 gap junctions in heart tissue, primary cardiomyocytes and cell culture models. The loss of myosin VI via siRNA-mediated knock down or isolation of primary cardiac tissue and fibroblasts from the myosin VI-null mouse results in reduced GJ plaque size with a concomitant reduction in intercellular communication as shown by FRAP and a new method of selective calcein administration. Analysis of the molecular role of myosin VI in Cx43 trafficking indicates that myosin VI is dispensable in the delivery of Cx43 to the cell surface and connexon movement in the plasma membrane...
January 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28092346/differential-hypothalamic-leptin-sensitivity-in-obese-rat-offspring-exposed-to-maternal-and-postnatal-intake-of-chocolate-and-soft-drink
#3
M Kjaergaard, C Nilsson, A Secher, J Kildegaard, T Skovgaard, M O Nielsen, K Grove, K Raun
BACKGROUND/OBJECTIVE: Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic astrocyte morphology in adult rat offspring. METHODS: Pregnant Sprague-Dawley rats were fed ad libitum chow diet only (C) or with chocolate and high sucrose soft drink supplement (S)...
January 16, 2017: Nutrition & Diabetes
https://www.readbyqxmd.com/read/28089846/modulation-of-neuroinflammation-and-pathology-in-the-5xfad-mouse-model-of-alzheimer-s-disease-using-a-biased-and-selective-beta-1-adrenergic-receptor-partial-agonist
#4
Pooneh Memar Ardestani, Andrew K Evans, Bitna Yi, Tiffany Nguyen, Laurence Coutellier, Mehrdad Shamloo
Degeneration of noradrenergic neurons occurs at an early stage of Alzheimer's Disease (AD). The noradrenergic system regulates arousal and learning and memory, and has been implicated in regulating neuroinflammation. Loss of noradrenergic tone may underlie AD progression at many levels. We have previously shown that acute administration of a partial agonist of the beta-1 adrenergic receptor (ADRB1), xamoterol, restores behavioral deficits in a mouse model of AD. The current studies examined the effects of chronic low dose xamoterol on neuroinflammation, pathology, and behavior in the pathologically aggressive 5XFAD transgenic mouse model of AD...
January 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28088077/rhoa-knockdown-by-cationic-amphiphilic-copolymer-sirhoa-polyplexes-enhances-axonal-regeneration-in-rat-spinal-cord-injury-model
#5
So-Jung Gwak, Christian Macks, Da Un Jeong, Mark Kindy, Michael Lynn, Ken Webb, Jeoung Soo Lee
Spinal cord injury (SCI) results in permanent loss of motor and sensory function due to developmentally-related and injured-induced changes in the extrinsic microenvironment and intrinsic neuronal biochemistry that limit plasticity and axonal regeneration. Our long term goal is to develop cationic, amphiphilic copolymers (poly (lactide-co-glycolide)-g-polyethylenimine, PgP) for combinatorial delivery of therapeutic nucleic acids (TNAs) and drugs targeting these different barriers. In this study, we evaluated the ability of PgP to deliver siRNA targeting RhoA, a critical signaling pathway activated by multiple extracellular inhibitors of axonal regeneration...
January 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28070857/a-small-organic-compound-mimicking-the-l1-cell-adhesion-molecule-promotes-functional-recovery-after-spinal-cord-injury-in-zebrafish
#6
Sudhanshu Sahu, Zhihua Zhang, Rong Li, Junkai Hu, Huifan Shen, Gabriele Loers, Yanqin Shen, Melitta Schachner
Tacrine is a small organic compound that was discovered to mimic the functions of the neural cell adhesion molecule L1 by promoting the cognate functions of L1 in vitro, such as neuronal survival, neuronal migration, neurite outgrowth, and myelination. Based on studies indicating that L1 enhances functional recovery in different central and peripheral nervous system disease paradigms of rodents, it deemed interesting to investigate the beneficial role of tacrine in the attractive zebrafish animal model, by evaluating functional recovery after spinal cord injury...
January 9, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28068342/neuropathogenesis-of-zika-virus-in-a-highly-susceptible-immunocompetent-mouse-model-after-antibody-blockade-of-type-i-interferon
#7
Darci R Smith, Bradley Hollidge, Sharon Daye, Xiankun Zeng, Candace Blancett, Kyle Kuszpit, Thomas Bocan, Jeff W Koehler, Susan Coyne, Tim Minogue, Tara Kenny, Xiaoli Chi, Soojin Yim, Lynn Miller, Connie Schmaljohn, Sina Bavari, Joseph W Golden
Animal models are needed to better understand the pathogenic mechanisms of Zika virus (ZIKV) and to evaluate candidate medical countermeasures. Adult mice infected with ZIKV develop a transient viremia, but do not demonstrate signs of morbidity or mortality. Mice deficient in type I or a combination of type I and type II interferon (IFN) responses are highly susceptible to ZIKV infection; however, the absence of a competent immune system limits their usefulness for studying medical countermeasures. Here we employ a murine model for ZIKV using wild-type C57BL/6 mice treated with an antibody to disrupt type I IFN signaling to study ZIKV pathogenesis...
January 9, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28059863/spatiotemporal-expression-of-ski-after-rat-spinal-cord-injury
#8
Kaisheng Zhou, Wei Nan, Dongliang Feng, Zhigang Yi, Yandong Zhu, Zaiyun Long, Sen Li, Haihong Zhang, Yamin Wu
Ski is an evolutionarily conserved protein and widely participates in the regulation of various pathological and physiological processes such as wound healing, liver regeneration, development of the embryonic nervous system, muscle differentiation, and progression of many kinds of tumors. However, the distribution and function of Ski in central nervous system lesion and disease remain unclear. In this study, we investigated the spatiotemporal expression of Ski in a spinal cord injury (SCI) model in adult rats...
January 2, 2017: Neuroreport
https://www.readbyqxmd.com/read/28059803/whole-body-vibration-wbv-following-spinal-cord-injury-sci-in-rats-timing-of-intervention
#9
Marilena Manthou, Diana Saad Yousif Abdulla, Stoyan Pavlov Pavlov, Ramona Jansen, Habib Bendella, Klaus Nohroudi, Gregor Stein, Carolin Mmeyer, Ozlem Ozsoy, Umut Ozsoy, Yasemin Behram Kandemir, Levent Sarikcioglu, Oliver Semler, Eckhard Schoenau, Sarah Dunlop, Doychin Nikolov Angelov
BACKGROUND: Following spinal cord injury (SCI), exercise training provides a wide range of benefits and promotes activity-dependent synaptic plasticity. Whole body vibration (WBV) in SCI patients improves walking and spasticity as well as bone and muscle mass. However, little is known about the effects of timing or frequency of intervention. OBJECTIVE: To determine which WBV-onset improves locomotor and bladder functions and influences synaptic plasticity beneficially...
January 4, 2017: Restorative Neurology and Neuroscience
https://www.readbyqxmd.com/read/28057555/reactive-astrogliosis-in-stroke-contributions-of-astrocytes-to-recovery-of-neurological-function
#10
REVIEW
Neil R Sims, Wai Ping Yew
Alterations in neuronal connectivity, particularly in the "peri-infarct" tissue adjacent to the region of ischemic damage, are important contributors to the spontaneous recovery of function that commonly follows stroke. Peri-infarct astrocytes undergo reactive astrogliosis and play key roles in modulating the adaptive responses in neurons. This reactive astrogliosis shares many features with that induced by other forms of damage to the central nervous system but also differs in details that potentially influence neurological recovery...
January 2, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28057080/combination-of-alpha-synuclein-immunotherapy-with-anti-inflammatory-treatment-in-a-transgenic-mouse-model-of-multiple-system-atrophy
#11
Elvira Valera, Brian Spencer, Jerel A Fields, Ivy Trinh, Anthony Adame, Michael Mante, Edward Rockenstein, Paula Desplats, Eliezer Masliah
Multiple system atrophy (MSA) is a fatal neurodegenerative disorder characterized by the pathological accumulation of alpha-synuclein (α-syn) in oligodendrocytes. Therapeutic efforts to stop or delay the progression of MSA have yielded suboptimal results in clinical trials, and there are no efficient treatments currently available for MSA patients. We hypothesize that combining therapies targeting different aspects of the disease may lead to better clinical outcomes. To test this hypothesis, we combined the use of a single-chain antibody targeting α-syn modified for improved central nervous system penetration (CD5-D5) with an unconventional anti-inflammatory treatment (lenalidomide) in the myelin basic protein (MBP)-α-syn transgenic mouse model of MSA...
January 5, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28056603/epigallocatechin-3-gallate-attenuates-acrylamide-induced-apoptosis-and-astrogliosis-in-rat-cerebral-cortex
#12
Yin He, Dehong Tan, Bing Bai, Zhaoxia Wu, Shujuan Ji
The potent neurotoxic agent acrylamide (ACR) is formed during Maillard reaction in food processing. Epigallocatechin-3-gallate (EGCG), a major bioactive component of green tea, is an antioxidant, but its effects on ACR-induced neurotoxicity are unclear. Here, we investigated the neuroprotective effects of EGCG against ACR-induced apoptosis and astrogliosis in the cerebral cortex. Rats were pretreated with EGCG for 4 d and then co-administered ACR for 14 d. Immunohistochemical analysis of glial fibrillary acidic protein and 8-hydroxy-2'-deoxyguanosine indicated that EGCG attenuated astrogliosis and DNA damage in ACR treated rats...
January 5, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28041911/disinhibition-of-the-intergeniculate-leaflet-network-in-the-wag-rij-rat-model-of-absence-epilepsy
#13
Lukasz Chrobok, Katarzyna Palus, Jagoda Stanislawa Jeczmien-Lazur, Anna Chrzanowska, Mariusz Kepczynski, Marian Henryk Lewandowski
The intergeniculate leaflet (IGL) of the thalamus is a retinorecipient structure implicated in orchestrating circadian rhythmicity. The IGL network is highly GABAergic and consists mainly of neuropeptide Y-synthesising and enkephalinergic neurons. A high density of GFAP-immunoreactive astrocytes has been observed in the IGL, with a probable function in guarding neuronal inhibition. Interestingly, putatively enkephalinergic IGL neurons generate action potentials with an infra-slow oscillatory (ISO) pattern in vivo in urethane anesthetised Wistar rats, under light-on conditions only...
December 30, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/28038988/serial-in-vivo-imaging-of-transplanted-allogeneic-neural-stem-cell-survival-in-a-mouse-model-of-amyotrophic-lateral-sclerosis
#14
Amit K Srivastava, Sarah K Gross, Akshata A Almad, Camille A Bulte, Nicholas J Maragakis, Jeff W M Bulte
Neural stem cells (NSCs) are being investigated as a possible treatment for amyotrophic lateral sclerosis (ALS) through intraspinal transplantation, but no longitudinal imaging studies exist that describe the survival of engrafted cells over time. Allogeneic firefly luciferase-expressing murine NSCs (Luc(+)-NSCs) were transplanted bilaterally (100,000 cells/2μl) into the cervical spinal cord (C5) parenchyma of pre-symptomatic (63day-old) SOD1(G93A) ALS mice (n=14) and wild-type age-matched littermates (n=14)...
December 28, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/28028152/pharmacologic-inhibition-of-hsp90-to-prevent-glt-1-degradation-as-an-effective-therapy-for-epilepsy
#15
Longze Sha, Xueqin Wang, Jing Li, Xinze Shi, Liwen Wu, Yan Shen, Qi Xu
The glutamate transporter GLT-1 is critical for the maintenance of low interstitial glutamate concentrations. Loss of GLT-1 is commonly observed in neurological disorders, including temporal lobe epilepsy (TLE). Despite the hypothesis that targeting the mechanisms of GLT-1 deficiency may be a novel strategy for treating drug-resistant epilepsy, the underlying molecular cascade remains largely unknown. Here, we show that Hsp90β is up-regulated in reactive astrocytes of the epileptic hippocampus in patients with TLE and mouse models of epilepsy...
December 27, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28013092/overexpression-of-mitofusin2-decreased-the-reactive-astrocytes-proliferation-in-vitro-induced-by-oxygen-glucose-deprivation-reoxygenation
#16
Yulong Shi, Chengla Yi, Xiao Li, Jiangpeng Wang, Fangyuan Zhou, Xiaoqian Chen
Glia scar is a hallmark in late-stage of brain stroke disease, which hinder axonal regeneration and neuronal repair. Mitofusin2 (Mfn2) is a newly found cellular proliferation inhibitor. This study is to elucidate the role of Mfn2 in reactive astrocytes induced by oxygen-glucose deprivation/reoxygenation(OGD/R) model in vitro. Up-expression in EdU staining and protein level of GFAP, PCNA and CyclinD1, demonstrates the distinct activation and proliferation of astrocytes after the stimulation of OGD/R. Meanwhile, Mfn2 was proved to be down-regulated both in gene and protein levels...
December 22, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/28012949/cannabidiol-reduces-brain-damage-and-improves-functional-recovery-in-a-neonatal-rat-model-of-arterial-ischemic-stroke
#17
Maria Ceprián, Laura Jiménez-Sánchez, Carlos Vargas, Lorena Barata, Will Hind, Jose Martínez-Orgado
BACKGROUND: and purpose: Currently there is no effective treatment for neonatal arterial ischemic stroke (AIS). Cannabidiol (CBD) is neuroprotective in models of newborn hypoxic-ischemic brain damage and adult stroke. The purpose of this work was to study the protective effect of CBD in a neonatal rat model of AIS. METHODS: Middle Cerebral Artery Occlusion (MCAO) was achieved in neonatal Wistar rats by introducing a nylon filament to the left MCA for 3 h; 15 min after removing the occluder vehicle (MCAO-V) or CBD single dose 5 mg/kg (MCAO-C) were administered i...
December 21, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28011042/glial-changes-and-evidence-for-apoptosis-in-the-brain-of-cats-infected-by-cytauxzoon-felis
#18
L L Clarke, P M Krimer, D R Rissi
Ischaemic neuropathological changes associated with Cytauxzoon felis infection in cats have been reported recently. This paper describes the associated glial changes and the evidence for apoptosis in the brain of cats infected naturally by C. felis. Sections of brain from eight affected cats and eight age- and sex-matched control cats were evaluated by immunohistochemistry for expression of glial fibrillary acidic protein, CD18 and cleaved caspase-3. Vascular changes in the leptomeninges and parenchyma, the number of positive astrocytes and phagocytic cells (microglia or macrophages) and the average astrocytic cytoplasmic area and number and length of astrocytic processes were quantified, and a mean value for the grey and white matter in both groups was generated...
December 20, 2016: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28008682/homozygous-ppt1-splice-donor-mutation-in-a-cane-corso-dog-with-neuronal-ceroid-lipofuscinosis
#19
A Kolicheski, H L Barnes Heller, S Arnold, R D Schnabel, J F Taylor, C A Knox, T Mhlanga-Mutangadura, D P O'Brien, G S Johnson, J Dreyfus, M L Katz
A 10-month-old spayed female Cane Corso dog was evaluated after a 2-month history of progressive blindness, ataxia, and lethargy. Neurologic examination abnormalities indicated a multifocal lesion with primarily cerebral and cerebellar signs. Clinical worsening resulted in humane euthanasia. On necropsy, there was marked astrogliosis throughout white matter tracts of the cerebrum, most prominently in the corpus callosum. In the cerebral cortex and midbrain, most neurons contained large amounts of autofluorescent storage material in the perinuclear area of the cells...
December 23, 2016: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/27999370/effect-of-lead-pb-on-inflammatory-processes-in-the-brain
#20
REVIEW
Karina Chibowska, Irena Baranowska-Bosiacka, Anna Falkowska, Izabela Gutowska, Marta Goschorska, Dariusz Chlubek
That the nervous system is the main target of lead (Pb) has long been considered an established fact until recent evidence has linked the Pb effect on the immune system to the toxic effects of Pb on the nervous system. In this paper, we present recent literature reports on the effect of Pb on the inflammatory processes in the brain, particularly the expression of selected cytokines in the brain (interleukin 6, TGF-β1, interleukin 16, interleukin 18, and interleukin 10); expression and activity of enzymes participating in the inflammatory processes, such as cyclooxygenase 2, caspase 1, nitrogen oxide synthase (NOS 2) and proteases (carboxypeptidases, metalloproteinases and chymotrypsin); and the expression of purine receptors P2X4 and P2X7...
December 19, 2016: International Journal of Molecular Sciences
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