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https://www.readbyqxmd.com/read/28205585/neuronally-directed-effects-of-rxr-activation-in-a-mouse-model-of-alzheimer-s-disease
#1
M M Mariani, T Malm, R Lamb, T R Jay, L Neilson, B Casali, L Medarametla, G E Landreth
Alzheimer's disease (AD) is characterized by extensive neuron loss that accompanies profound impairments in memory and cognition. We examined the neuronally directed effects of the retinoid X receptor agonist bexarotene in an aggressive model of AD. We report that a two week treatment of 3.5 month old 5XFAD mice with bexarotene resulted in the clearance of intraneuronal amyloid deposits. Importantly, neuronal loss was attenuated by 44% in the subiculum in mice 4 months of age and 18% in layer V of the cortex in mice 8 months of age...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28204814/fisetin-regulates-astrocyte-migration-and-proliferation-in%C3%A2-vitro
#2
Nan Wang, Fang Yao, Ke Li, Lanlan Zhang, Guo Yin, Mingjun Du, Bingyi Wu
Fisetin (3,3',4',7-tetrahydroxyflavone) is a plant flavonol found in fruits and vegetables that has been reported to inhibit migration and proliferation in several types of cancer. Reactive astrogliosis involves astrocyte migration and proliferation, and contributes to the formation of glial scars in central nervous system (CNS) disorders. However, the effect of fisetin on the migration and proliferation of astrocytes remains unclear. In this study, we found that fisetin inhibited astrocyte migration in a scratch-wound assay and diminished the phosphorylation of focal adhesion kinase (FAK; Tyr576/577 and paxillin (Tyr118)...
February 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28199883/acetyl-l-carnitine-protects-dopaminergic-nigrostriatal-pathway-in-6-hydroxydopamine-induced-model-of-parkinson-s-disease-in-the-rat
#3
Siamak Afshin-Majd, Keyhan Bashiri, Zahra Kiasalari, Tourandokht Baluchnejadmojarad, Reza Sedaghat, Mehrdad Roghani
Parkinson's disease (PD) is a movement disorder and the second most common neurodegenerative disease worldwide in which nigrostriatal dopaminergic neurons within substantia nigra pars compacta (SNC) are lost, with clinical motor and non-motor symptoms including bradykinesia, resting tremor, rigidity, stooping posture and cognitive deficits. This study was undertaken to evaluate the neuroprotective potential of acetyl-l-carnitine (ALC) against unilateral striatal 6-hydroxydopamine (6-OHDA)-induced model of PD and to explore some involved mechanisms...
February 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28196893/phosphorylation-of-%C3%AE-b-crystallin-supports-reactive-astrogliosis-in-demyelination
#4
Hedwich F Kuipers, Jane Yoon, Jack van Horssen, May H Han, Paul L Bollyky, Theo D Palmer, Lawrence Steinman
The small heat shock protein αB-crystallin (CRYAB) has been implicated in multiple sclerosis (MS) pathogenesis. Earlier studies have indicated that CRYAB inhibits inflammation and attenuates clinical disease when administered in the experimental autoimmune encephalomyelitis model of MS. In this study, we evaluated the role of CRYAB in primary demyelinating events. Using the cuprizone model of demyelination, a noninflammatory model that allows the analysis of glial responses in MS, we show that endogenous CRYAB expression is associated with increased severity of demyelination...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193238/transient-ikk2-activation-in-astrocytes-initiates-selective-non-cell-autonomous-neurodegeneration
#5
Michael Lattke, Stephanie N Reichel, Alexander Magnutzki, Alireza Abaei, Volker Rasche, Paul Walther, Dinis P Calado, Boris Ferger, Thomas Wirth, Bernd Baumann
BACKGROUND: Neuroinflammation is associated with a wide range of neurodegenerative disorders, however the specific contribution to individual disease pathogenesis and selective neuronal cell death is not well understood. Inflammatory cerebellar ataxias are neurodegenerative diseases occurring in various autoimmune/inflammatory conditions, e.g. paraneoplastic syndromes. However, how inflammatory insults can cause selective cerebellar neurodegeneration in the context of these diseases remains open, and appropriate animal models are lacking...
February 13, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28192611/deficiency-of-trek-1-potassium-channel-exacerbates-secondary-injury-following-spinal-cord-injury-in-mice
#6
Yongkang Fang, Xiaojiang Huang, Yue Wan, Hao Tian, Yeye Tian, Wei Wang, Suiqiang Zhu, Minjie Xie
Spinal cord injury (SCI) involves complex pathological process which can be complicated by secondary injury. TREK-1 is a member of the two-pore domain potassium (K2P) channel family, which can be modulated by a number of physiological and pathological stimuli. Recent studies suggest that TREK-1 plays an active role in depression, pain and neuroprotection. However, its role in the pathological process after SCI remains unclear. In this study, we tested the expression and function of TREK-1 in spinal cord of mice after traumatic SCI...
February 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28181797/a-thermosensitive-heparin-poloxamer-hydrogel-bridge-afgf-to-treat-spinal-cord-injury
#7
Qingqing Wang, Yan He, Yingzheng Zhao, Huixu Xie, Qian Lin, Zili He, Xiaoyan Wang, Jiawei Li, Hongyu Zhang, Chenggui Wang, Fanghua Gong, Xiaokun Li, Huazi Xu, Qingsong Ye, Jian Xiao
Acidic fibroblast growth factor (aFGF) exerts a protective effect on spinal cord injury (SCI) but is limited by the lack of physicochemical stability andthe ability to cross the blood spinal cord barrier (BSCB). As promising biomaterials, hydrogels contain substantial amounts of water and a 3D porous structureand are commonly used to load and deliver growth factors. Heparin can not only enhance growth factor loading onto hydrogels but also can stabilize the structure and control the release behavior. Herein, a novel aFGF-loaded thermosensitive heparin-poloxamer (aFGF-HP) hydrogel was developed and applied to provide protection and regeneration after SCI...
February 9, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28176234/frequent-mild-head-injury-promotes-trigeminal-sensitivity-concomitant-with-microglial-proliferation-astrocytosis-and-increased-neuropeptide-levels-in-the-trigeminal-pain-system
#8
Ashley L Tyburski, Lan Cheng, Soroush Assari, Kurosh Darvish, Melanie B Elliott
BACKGROUND: Frequent mild head injuries or concussion along with the presence of headache may contribute to the persistence of concussion symptoms. METHODS: In this study, the acute effects of recovery between mild head injuries and the frequency of injuries on a headache behavior, trigeminal allodynia, was assessed using von Frey testing up to one week after injury, while histopathological changes in the trigeminal pain pathway were evaluated using western blot, ELISA and immunohistochemistry...
December 2017: Journal of Headache and Pain
https://www.readbyqxmd.com/read/28174044/propylparaben-applied-after-pilocarpine-induced-status-epilepticus-modifies-hippocampal-excitability-and-glutamate-release-in-rats
#9
César Emmanuel Santana-Gómez, Sandra Adela Orozco-Suárez, Alan Talevi, Luis Bruno-Blanch, Víctor Manuel Magdaleno-Madrigal, Rodrigo Fernández-Mas, Luisa Rocha
Propylparaben (PPB) induces cardioprotection after ischemia-reperfusion injury by inhibiting voltage-dependent Na(+) channels. The present study focuses on investigating whether the i.p. application of 178mg/kg PPB after pilocarpine-induced status epilepticus (SE) reduces the acute and long-term consequences of seizure activity. Initially, we investigated the effects of a single administration of PPB after SE. Our results revealed that compared to rats receiving diazepam (DZP) plus vehicle after 2h of SE, animals receiving a single dose of PPB 1h after DZP injection presented 126% (p<0...
February 4, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28167801/caspase-3-and-gfap-as-early-markers-for-apoptosis-and-astrogliosis-in-shrna-induced-hippocampal-cytotoxicity
#10
Anne Günther, Vince Luczak, Ted Abel, Arnd Baumann
Genetic manipulation of cells and tissue by RNA interference has significantly contributed to the functional characterization of individual proteins and their role in physiological processes. Despite its versatility, RNA interference can have detrimental side effects, including reduced cell viability. We applied recombinant adeno-associated viruses by stereotaxic injection into the murine hippocampus to express different short hairpin RNA (shRNA) constructs along with eGFP. Tissue responses were assessed immunohistochemically for up to 8 weeks post infection...
February 6, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28157651/sesamin-imparts-neuroprotection-against-intrastriatal-6-hydroxydopamine-toxicity-by-inhibition-of-astroglial-activation-apoptosis-and-oxidative-stress
#11
Tourandokht Baluchnejadmojarad, Monireh Mansouri, Jamileh Ghalami, Zahra Mokhtari, Mehrdad Roghani
Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders in elders. Sesamin is a lignan compound and the active constituent of sesame oil with antioxidant and anti-inflammatory properties. This study was carried out to explore the mechanisms underlying sesamin effect against unilateral striatal 6-hydroxydopamine (6-OHDA) model of PD. Intrastriatal 6-OHDA-lesioned rats were pretreated with sesamin at doses of 10 or 20mg/kg/day for one week. Sesamin at a dose of 20mg/kg attenuated motor imbalance in narrow beam test, lowered striatal level of malondialdehyde (MDA) and reactive oxygen species (ROS), improved superoxide dismutase (SOD) activity, lowered striatal caspase 3 activity and α-synuclein expression, attenuated glial fibrillary acidic protein (GFAP) immunoreactivity, depressed nigral neuronal apoptosis, and prevented damage of dopaminergic neurons using tyrosine hydroxylase (TH) immunohistochemistry...
January 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28153522/cdk5-inhibitors-prevent-astroglial-apoptosis-and-reactive-astrogliosis-by-regulating-pka-and-drp1-phosphorylations-in-the-rat-hippocampus
#12
Hye-Won Hyun, Su-Ji Min, Ji-Eun Kim
Status epilepticus (SE) results in the unique pattern of dynamin-related protein 1 (DRP1)-mediated mitochondrial dynamics, which is associated with astroglial apoptosis and reactive astrogliosis in the regional-specific pattern representing the differential astroglial properties. However, less defined are the epiphenomena/upstream effecters for DRP1 phosphorylation in this process. Since cyclin-dependent kinase 5 (CDK5) is involved in reactive astrogliosis, CDK5 is one of the possible upstream regulators for DRP1 phosphorylation...
January 30, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28153091/effect-of-fingolimod-on-neural-stem-cells-a-novel-mechanism-and-broadened-application-for-neural-repair
#13
Yuan Zhang, Xing Li, Bogoljub Ciric, Cun-Gen Ma, Bruno Gran, Abdolmohamad Rostami, Guang-Xian Zhang
Inflammatory demyelination and axonal damage of the CNS are hallmarks of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Fingolimod (FTY720), the first FDA-approved oral medication for MS, suppresses acute disease but is less effective at the chronic stage, and whether it has a direct effect on neuroregeneration in MS and EAE remains unclear. Here we show that FTY720, at nanomolar concentrations, effectively protected survival of neural stem cells (NSCs) and enhanced their development into mature oligodendrocytes (OLGs) in vitro, primarily through the S1P3 and S1P5 receptors...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28151476/regulation-of-glutamate-transporter-trafficking-by-nedd4-2-in-a-parkinson-s-disease-model
#14
Yunlong Zhang, Xiaoliang He, Xingjun Meng, Xiaojuan Wu, Huichun Tong, Xiuping Zhang, Shaogang Qu
Glutamate transporters play a key role in glutamate clearance and protect the central nervous system from glutamate excitotoxicity. Dysfunctional glutamate transporters contribute to the pathogenesis of Parkinson's disease (PD); however, the mechanisms that underlie the regulation of glutamate transporters in PD are still not well characterized. Here we report that Nedd4-2 mediates the ubiquitination of glutamate transporters in 1-methyl-4- phenylpyridinium (MPP(+))-treated astrocytes and in the midbrain of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-constructed PD model mice...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28148272/dose-dependent-induction-of-astrocyte-activation-and-reactive-astrogliosis-in-mouse-brain-following-maternal-exposure-to-carbon-black-nanoparticle
#15
Atsuto Onoda, Ken Takeda, Masakazu Umezawa
BACKGROUND: Recent studies indicate that maternal exposure to ambient ultrafine particles and nanoparticles has adverse effects of on the central nervous system. Quantitative dose-response data is required to better understand the developmental neurotoxicity of nanoparticles. The present study investigated dose-dependent effects of maternal exposure to carbon black nanoparticle (CB-NP) on astrocyte in the brains of mouse offspring. METHODS: A CB-NP suspension (2...
2, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28128448/chronic-infusion-of-sod1-g93a-astrocyte-secreted-factors-induces-spinal-motoneuron-degeneration-and-neuromuscular-dysfunction-in-healthy-rats
#16
U N Ramírez-Jarquín, F Rojas, B van Zundert, R Tapia
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease and studies in vitro show that motoneuron degeneration is triggered by non-cell-autonomous mechanisms. However, whether soluble toxic factor(s) released by mutant superoxide dismutase 1 (SOD1) expressing astrocytes induces death of motoneurons and leads to motor dysfunction in vivo is not known. To directly test this, healthy adult rats were treated with conditioned media derived from primary mouse astrocytes (ACM) that express human (h) SOD1(G93A) (ACM-hG93A) via chronic osmotic pump infusion in the lumbar spinal cord...
January 27, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28128219/astrocyte-derived-tissue-transglutaminase-affects-fibronectin-deposition-but-not-aggregation-during-cuprizone-induced-demyelination
#17
Nathaly Espitia Pinzon, Berta Sanz-Morello, John J P Brevé, John G J M Bol, Benjamin Drukarch, Jan Bauer, Wia Baron, Anne-Marie van Dam
Astrogliosis as seen in Multiple Sclerosis (MS) develops into astroglial scarring, which is beneficial because it seals off the site of central nervous system (CNS) damage. However, astroglial scarring also forms an obstacle that inhibits axon outgrowth and (re)myelination in brain lesions. This is possibly an important cause for incomplete remyelination in the CNS of early stage MS patients and for failure in remyelination when the disease progresses. In this study we address whether under demyelinating conditions in vivo, tissue Transglutaminase (TG2), a Ca(2+) -dependent enzyme that catalyses posttranslational modification of proteins, contributes to extracellular matrix (ECM) deposition and/or aggregation...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28114090/-pro-inflammatory-cytokines-in-alzheimer-s-disease
#18
E C Stamouli, A M Politis
Alzheimer's disease (AD), the most common progressive neurodegenerative disorder in the elderly, is clinically characterized by progressive impairment of cognitive functions, including reduced critical capacity, weakness of decision-making and problem orientation, while in the more advanced stages it is accompanied by behavioral disorders and impaired verbal ability. Neuropathological characteristics of the disease are the neurofibrillary tangles (NFT), the neuritic plaques (NP), the prominent synaptic loss and eventually the neuronal loss...
October 2016: Psychiatrikē, Psychiatriki
https://www.readbyqxmd.com/read/28110393/nitric-oxide-production-in-the-striatum-and-cerebellum-of-a-rat-model-of-preterm-global-perinatal-asphyxia
#19
M Barkhuizen, W D J Van de Berg, J De Vente, C E Blanco, A W D Gavilanes, H W M Steinbusch
Encephalopathy due to perinatal asphyxia (PA) is a major cause of neonatal morbidity and mortality in the period around birth. Preterm infants are especially at risk for cognitive, attention and motor impairments. Therapy for this subgroup is limited to supportive care, and new targets are thus urgently needed. Post-asphyxic excitotoxicity is partially mediated by excessive nitric oxide (NO) release. The aims of this study were to determine the timing and distribution of nitric oxide (NO) production after global PA in brain areas involved in motor regulation and coordination...
January 21, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28107387/neuronal-cell-death-and-degeneration-through-increased-nitroxidative-stress-and-tau-phosphorylation-in-hiv-1-transgenic-rats
#20
Young-Eun Cho, Myoung-Hwa Lee, Byoung-Joon Song
The underlying mechanisms for increased neurodegeneration and neurocognitive deficits in HIV-infected people are unclear. Therefore, this study was aimed to investigate the mechanisms of increased neurodegeneration in 5-month old male HIV-1 Transgenic (Tg) rats compared to the age- and gender-matched wild-type (WT) by evaluating histological changes and biochemical parameters of the key proteins involved in the cell death signaling and apoptosis. Histological and immunohistochemical analyses revealed decreased neuronal cells with elevated astrogliosis in HIV-1 Tg rats compared to WT...
2017: PloS One
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