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https://www.readbyqxmd.com/read/29241654/ginsenoside-rb1-confers-neuroprotection-via-promotion-of-glutamate-transporters-in-a-mouse-model-of-parkinson-s-disease
#1
Yun-Long Zhang, Yan Liu, Xin-Pan Kang, Chun-Yan Dou, Ren-Gong Zhuo, Shu-Qiong Huang, Li Peng, Lei Wen
Ginsenoside Rb1 has been demonstrated to protect dopaminergic (DA) neurons from death in vitro. However, the neuroprotective effects and underlying mechanism of Rb1 in treating Parkinson's disease (PD) remain uncharacterized. In this study, we explored the effects of Rb1 on the movement disorder and the underlying mechanisms based on the glutamatergic transmission and excitotoxicity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Here, for the first time, we report that Rb1 treatment ameliorates motor deficits, prevents DA neuron death, and suppresses α-synuclein expression and astrogliosis in the MPTP mouse model of PD...
December 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29238610/a-role-for-erbb-signaling-in-the-induction-of-reactive-astrogliosis
#2
Jing Chen, Wanwan He, Xu Hu, Yuwen Shen, Junyan Cao, Zhengdong Wei, Yifei Luan, Li He, Fangdun Jiang, Yanmei Tao
Reactive astrogliosis is a hallmark of many neurological disorders, yet its functions and molecular mechanisms remain elusive. Particularly, the upstream signaling that regulates pathological responses of astrocytes is largely undetermined. We used a mouse traumatic brain injury model to induce astrogliosis and revealed activation of ErbB receptors in reactive astrocytes. Moreover, cell-autonomous inhibition of ErbB receptor activity in reactive astrocytes by a genetic approach suppressed hypertrophic remodeling possibly through the regulation of actin dynamics...
2017: Cell Discovery
https://www.readbyqxmd.com/read/29236326/knockdown-of-ski-decreased-the-reactive-astrocytes-proliferation-in-vitro-induced-by-oxygen-glucose-deprivation-reoxygenation
#3
Xin Zhao, Kai-Sheng Zhou, Zhong-Hao Li, Wei Nan, Jing Wang, Ya-Yi Xia, Hai-Hong Zhang
Glia scar is a pathological marker in late phase of brain ischemia disease, which constitutes a major physical biochemical barrier to impede axonal regrowth. Astrocytes are known to be critically involved in the formation of glial scar. However, their response to ischemia and their role in neuroprotection after central nervous system (CNS) injury are not completely clear. Recently, we have demonstrated for the first time that Ski was up-regulated in reactive astrocytes after spinal cord injury in vivo and in vitro, which indicates Ski may be a new molecule that control astrocytes biologic properties after CNS injury...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29235064/induction-of-neuroinflammatory-response-and-histopathological-alterations-caused-by-quinolinic-acid-administration-in-the-striatum-of-glutaryl-coa-dehydrogenase-deficient-mice
#4
Alexandre Umpierrez Amaral, Bianca Seminotti, Janaína Camacho da Silva, Francine Hehn de Oliveira, Rafael Teixeira Ribeiro, Carmen Regla Vargas, Guilhian Leipnitz, Abel Santamaría, Diogo Onofre Souza, Moacir Wajner
Glutaric acidemia type I (GA I) is an inherited neurometabolic disorder caused by a severe deficiency of the mitochondrial glutaryl-CoA dehydrogenase (GCDH) activity. Patients usually present progressive cortical leukodystrophy and commonly develop acute bilateral striatal degeneration mainly during infections that markedly worse their prognosis. A role for quinolinic acid (QA), a key metabolite of the kynurenine pathway, which is activated during inflammatory processes, on the pathogenesis of the acute striatum degeneration occurring in GA I was proposed but so far has not yet been evaluated...
December 12, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29230441/detection-of-a%C3%AE-plaque-associated-astrogliosis-in-alzheimer-s-disease-brain-by-spectroscopic-imaging-and-immunohistochemistry
#5
Francesca Palombo, Francesco Tamagnini, J Charles G Jeynes, Sara Mattana, Imogen Swift, Jayakrupakar Nallala, Jane Hancock, Jonathan T Brown, Andrew D Randall, Nick Stone
Recent work using micro-Fourier transform infrared (μFTIR) imaging has revealed that a lipid-rich layer surrounds many plaques in post-mortem Alzheimer's brain. However, the origin of this lipid layer is not known, nor is its role in the pathogenesis of Alzheimer's disease (AD). Here, we studied the biochemistry of plaques in situ using a model of AD. We combined FTIR, Raman and immunofluorescence images, showing that astrocyte processes co-localise with the lipid ring surrounding many plaques. We used μFTIR imaging to rapidly measure chemical signatures of plaques over large fields of view, and selected plaques for higher resolution analysis with Raman microscopy...
December 12, 2017: Analyst
https://www.readbyqxmd.com/read/29229355/effects-of-biflavonoids-from-garcinia-madruno-on-a-triple-transgenic-mouse-model-of-alzheimer-s-disease
#6
Angélica Maria Sabogal-Guáqueta, Luis Carrillo-Hormaza, Edison Osorio, Gloria Patricia Cardona-Gómez
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is pathologically characterized by the deposition of β-amyloid (βA) peptides in senile plaques and neurofibrillary tangles in the brain. Flavonoids have recently been used to prevent and treat a variety of neurodegenerative diseases, but little is known about bioflavonoids. In this study, we evaluate whether a biflavonoid fraction (BF) exerts neuroprotective effects on an aged triple transgenic mouse mode of AD (3xTg-AD). Then, 21-24-month-old 3xTg AD mice were i...
December 8, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29228979/contrasting-effect-of-the-latency-reversing-agents-bryostatin-1-and-jq1-on-astrocyte-mediated-neuroinflammation-and-brain-neutrophil-invasion
#7
Alizé Proust, Corinne Barat, Mathieu Leboeuf, Jean Drouin, Michel J Tremblay
BACKGROUND: Despite effectiveness of the combined antiretroviral therapy, HIV-1 persists in long-lived latently infected cells. Consequently, new therapeutic approaches aimed at eliminating this latent reservoir are currently being developed. A "shock and kill" strategy using latency-reversing agents (LRA) to reactivate HIV-1 has been proposed. However, the impact of LRA on the central nervous system (CNS) remains elusive. METHODS: We used human fetal astrocytes and investigated the effects of several LRA on their functional and secretory activities...
December 11, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29212737/astrocytic-lrp4-low-density-lipoprotein-receptor-related-protein-4-contributes-to-ischemia-induced-brain-injury-by-regulating-atp-release-and-adenosine-a2ar-adenosine-a2a-receptor-signaling
#8
Xin-Chun Ye, Jin-Xia Hu, Lei Li, Qiang Li, Fu-Lei Tang, Sen Lin, Dong Sun, Xiang-Dong Sun, Gui-Yun Cui, Lin Mei, Wen-Cheng Xiong
BACKGROUND AND PURPOSE: Lrp4 (low-density lipoprotein receptor-related protein 4) is predominantly expressed in astrocytes, where it regulates glutamatergic neurotransmission by suppressing ATP release. Here, we investigated Lrp4's function in ischemia/stroke-induced brain injury response, which includes glutamate-induced neuronal death and reactive astrogliosis. METHODS: The brain-specific Lrp4 conditional knockout mice (Lrp4GFAP-Cre), astrocytic-specific Lrp4 conditional knockout mice (Lrp4GFAP-creER), and their control mice (Lrp4f/f) were subjected to photothrombotic ischemia and the transient middle cerebral artery occlusion...
December 6, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29208469/an-elastomeric-polymer-matrix-peuu-tac-delivers-bioactive-tacrolimus-transdurally-to-the-cns-in-rat
#9
Yolandi van der Merwe, Anne E Faust, Ian Conner, Xinzhu Gu, Firuz Feturi, Wenchen Zhao, Bianca Leonard, Souvik Roy, Vijay S Gorantla, Raman Venkataramanan, Kia M Washington, William R Wagner, Michael B Steketee
Central nervous system (CNS) neurons fail to regrow injured axons, often resulting in permanently lost neurologic function. Tacrolimus is an FDA-approved immunosuppressive drug with known neuroprotective and neuroregenerative properties in the CNS. However, tacrolimus is typically administered systemically and blood levels required to effectively treat CNS injuries can lead to lethal, off-target organ toxicity. Thus, delivering tacrolimus locally to CNS tissues may provide therapeutic control over tacrolimus levels in CNS tissues while minimizing off-target toxicity...
November 24, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29203398/metyrapone-prevents-acute-glucose-hypermetabolism-and-short-term-brain-damage-induced-by-intrahippocampal-administration-of-4-aminopyridine-in-rats
#10
Luis García-García, Rubén Fernández de la Rosa, Mercedes Delgado, Ágata Silván, Pablo Bascuñana, Jens P Bankstahl, Francisca Gomez, Miguel A Pozo
Intracerebral administration of the potassium channel blocker 4-aminopyridine (4-AP) triggers neuronal depolarization and intense acute seizure activity followed by neuronal damage. We have recently shown that, in the lithium-pilocarpine rat model of status epilepticus, a single administration of metyrapone, an inhibitor of the 11β-hydroxylase enzyme, had protective properties of preventive nature against signs of brain damage and neuroinflammation. Herein, our aim was to investigate to which extent, pretreatment with metyrapone (150 mg/kg, i...
December 1, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29203280/reduced-post-stroke-glial-scarring-in-the-infant-primate-brain-reflects-age-related-differences-in-the-regulation-of-astrogliosis
#11
Leon Teo, Anthony G Boghdadi, Mitchell de Souza, James A Bourne
Ischemic stroke remains a leading cause of disability worldwide. Surviving patients often suffer permanent neurological impairments, and spontaneous recovery rarely occurs. However, observations that early-life brain injuries, including strokes, elicit less severe long-term functional impairments, compared to adults, continue to intrigue. While much research has focussed on neuronal changes and plasticity, less is known regarding the regulation of astrogliosis and glial scar formation after a stroke at different stages of life...
December 1, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29201361/quercetin-prevents-spinal-motor-neuron-degeneration-induced-by-chronic-excitotoxic-stimulus-by-a-sirtuin-1-dependent-mechanism
#12
Rafael Lazo-Gomez, Ricardo Tapia
Background: Excitotoxicity is a mechanism of foremost importance in the selective motor neuron degeneration characteristic of motor neuron disorders. Effective therapeutic strategies are an unmet need for these disorders. Polyphenols, such as quercetin and resveratrol, are plant-derived compounds that activate sirtuins (SIRTs) and have shown promising results in some models of neuronal death, although their effects have been scarcely tested in models of motor neuron degeneration. Methods: In this work we investigated the effects of quercetin and resveratrol in an in vivo model of excitotoxic motor neuron death induced by the chronic infusion of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) into the rat spinal cord tissue...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29201025/regulation-of-neuroinflammation-what-role-for-the-tumor-necrosis-factor-like-weak-inducer-of-apoptosis-fn14-pathway
#13
REVIEW
Audrey Boulamery, Sophie Desplat-Jégo
Observed in many central nervous system diseases, neuroinflammation (NI) proceeds from peripheral immune cell infiltration into the parenchyma, from cytokine secretion and from oxidative stress. Astrocytes and microglia also get activated and proliferate. NI manifestations and consequences depend on its context and on the acute or chronic aspect of the disease. The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/Fn14 pathway has been involved in chronic human inflammatory pathologies such as neurodegenerative, autoimmune, or malignant diseases...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29196269/diffusion-mri-and-mr-spectroscopy-reveal-microstructural-and-metabolic-brain-alterations-in-chronic-mild-stress-exposed-rats-a-cms-recovery-study
#14
Ahmad Raza Khan, Brian Hansen, Ove Wiborg, Christopher D Kroenke, Sune Nørhøj Jespersen
Chronic mild stress (CMS) induced depression elicits several debilitating symptoms and causes a significant economic burden on society. High variability in the symptomatology of depression poses substantial impediment to accurate diagnosis and therapy outcome. CMS exposure induces significant metabolic and microstructural alterations in the hippocampus (HP), prefrontal cortex (PFC), caudate-putamen (CP) and amygdala (AM), however, recovery from these maladaptive changes are limited and this may provide negative effects on the therapeutic treatment and management of depression...
November 28, 2017: NeuroImage
https://www.readbyqxmd.com/read/29192919/oxidative-stress-induced-increase-of-intracellular-zinc-in-astrocytes-decreases-their-functional-expression-of-p2x7-receptors-and-engulfing-activity
#15
Takahiro Furuta, Ayumi Mukai, Akihiro Ohishi, Kentaro Nishida, Kazuki Nagasawa
Neuron-glia communication mediated by neuro- and glio-transmitters such as ATP and zinc is crucial for the maintenance of brain homeostasis, and its dysregulation is found under pathological conditions. It is reported that under oxidative stress-loaded conditions, astrocytes exhibit increased intra- and extra-cellular labile zinc, the latter triggering microglial M1 activation, while the pathophysiological role of the former remains unrevealed. In this study, we examined whether the oxidative stress-induced increase of intracellular labile zinc is involved in the P2X7 receptor (P2X7R)-mediated regulation of astrocytic engulfing activity...
December 1, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29186969/neuronal-and-astrocytic-involvement-in-striped-dolphins-stenella-coeruleoalba-with-morbilliviral-encephalitis
#16
R Lucá, R Giacominelli-Stuffler, S Mazzariol, S Roperto, C Cocumelli, G DI Guardo
Dolphin morbillivirus (DMV), a highly pathogenic agent, may cause peculiar, "brain-only" forms of infection (BOFDI), in which viral antigen and/or genome is found exclusively in the brain from striped dolphins (Stenella coeruleoalba). These BOFDIs show morphopathological similarities with subacute sclerosing panencephalitis and old dog encephalitis (ODE) in measles virus-infected patients and in canine distemper virus-infected dogs, respectively. The brain tissue from 3 BOFDI-affected striped dolphins was investigated by means of double labelling-indirect immunofluorescence (DL-IIF) and ultrastructurally, in order to characterize the DMV-targeted neuronal and non-neuronal cell populations, along with the associated submicroscopic findings...
2017: Acta Virologica
https://www.readbyqxmd.com/read/29186680/astrocytic-l-lactate-signaling-facilitates-amygdala-anterior-cingulate-cortex-synchrony-and-decision-making-in-rats
#17
Jun Wang, Jie Tu, Bing Cao, Li Mu, Xiangwei Yang, Mi Cong, Aruna S Ramkrishnan, Rosa H M Chan, Liping Wang, Ying Li
Human brain imaging studies have revealed the anterior cingulate cortex (ACC) as a key brain region for mediating visceral-pain-cognitive interactions. Recently, we characterized impairments of long-term potentiation and spike-field coherence in the basolateral amygdala (BLA)-ACC network in association with a decision-making deficit in rats with visceral hypersensitivity (VH). Now, by combining integrative neurobiological approaches, we show that ACC-reactive astrogliosis and activity-dependent impairment of lactate release occur in VH rats...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29180963/spinal-cord-molecular-and-cellular-changes-induced-by-adenoviral-vector-and-cell-mediated-triple-gene-therapy-after-severe-contusion
#18
Andrei A Izmailov, Tatyana V Povysheva, Farid V Bashirov, Mikhail E Sokolov, Filip O Fadeev, Ravil R Garifulin, Boris S Naroditsky, Denis Y Logunov, Ilnur I Salafutdinov, Yuri A Chelyshev, Rustem R Islamov, Igor A Lavrov
The gene therapy has been successful in treatment of spinal cord injury (SCI) in several animal models, although it still remains unavailable for clinical practice. Surprisingly, regardless the fact that multiple reports showed motor recovery with gene therapy, little is known about molecular and cellular changes in the post-traumatic spinal cord following viral vector- or cell-mediated gene therapy. In this study we evaluated the therapeutic efficacy and changes in spinal cord after treatment with the genes encoding vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG), and neuronal cell adhesion molecule (NCAM) applied using both approaches...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29178390/foxo-protects-against-age-progressive-axonal-degeneration
#19
Inah Hwang, Hwanhee Oh, Evan Santo, Do-Yeon Kim, John W Chen, Roderick T Bronson, Jason W Locasale, Yoonmi Na, Jaclyn Lee, Stewart Reed, Miklos Toth, Wai H Yu, Florian L Muller, Jihye Paik
Neurodegeneration resulting in cognitive and motor impairment is an inevitable consequence of aging. Little is known about the genetic regulation of this process despite its overriding importance in normal aging. Here, we identify the Forkhead Box O (FOXO) transcription factor 1, 3, and 4 isoforms as a guardian of neuronal integrity by inhibiting age-progressive axonal degeneration in mammals. FOXO expression progressively increased in aging human and mouse brains. The nervous system-specific deletion of Foxo transcription factors in mice accelerates aging-related axonal tract degeneration, which is followed by motor dysfunction...
November 26, 2017: Aging Cell
https://www.readbyqxmd.com/read/29178139/phagocytic-clearance-of-presynaptic-dystrophies-by-reactive-astrocytes-in-alzheimer-s-disease
#20
Angela Gomez-Arboledas, Jose C Davila, Elisabeth Sanchez-Mejias, Victoria Navarro, Cristina Nuñez-Diaz, Raquel Sanchez-Varo, Maria Virtudes Sanchez-Mico, Laura Trujillo-Estrada, Juan Jose Fernandez-Valenzuela, Marisa Vizuete, Joan X Comella, Elena Galea, Javier Vitorica, Antonia Gutierrez
Reactive astrogliosis, a complex process characterized by cell hypertrophy and upregulation of components of intermediate filaments, is a common feature in brains of Alzheimer's patients. Reactive astrocytes are found in close association with neuritic plaques; however, the precise role of these glial cells in disease pathogenesis is unknown. In this study, using immunohistochemical techniques and light and electron microscopy, we report that plaque-associated reactive astrocytes enwrap, engulf and may digest presynaptic dystrophies in the hippocampus of amyloid precursor protein/presenilin-1 (APP/PS1) mice...
November 27, 2017: Glia
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