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https://www.readbyqxmd.com/read/28214984/dl-3-n-butylphthalide-nbp-provides-neuroprotection-in-the-mice-models-after-traumatic-brain-injury-via-nrf2-are-signaling-pathway
#1
Zhengwei Liu, Handong Wang, Xiaofeng Shi, Liwen Li, Mengliang Zhou, Hui Ding, Youqing Yang, Xiang Li, Ke Ding
The present study was aimed to evaluate the neuroprotective effects of NBP in the mice models of TBI, as well as the possible role of Nrf2-ARE pathways in the assumptive neuroprotection. In mice,a modified Marmarou's weight-drop model was employed to induce TBI. ICR mice were randomly assigned to four experimental groups: sham, TBI, TBI+vehicle(V) and TBI+NBP. NBP (100 mg/kg) was administered via an intraperitoneal (i.p.) injection at 1 h following TBI. The administration of NBP significantly ameliorated the effects of the brain injury, including neurological deficits, brain water content, and cortical neuronal apoptosis...
February 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28214828/role-for-target-of-rapamycin-mtor-signal-pathway-in-regulating-neuronal-injury-after-intracerebral-hemorrhage
#2
Jie-Ping Wang, Meng-Yu Zhang
BACKGROUND/AIMS: Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and activation of its signal pathway plays an important role in regulating protein growth and synthesis as well as cell proliferation and survival. In the present study, we examined the contribution of mTOR signal and its downstream products to brain injuries induced by intracerebral hemorrhage (ICH) in rats. METHODS: Western Blot analysis was employed to examine the protein expression of mTOR and its downstream pathway and Caspase-3...
January 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214564/downregulation-of-gna13-erk-network-in-prefrontal-cortex-of-schizophrenia-brain-identified-by-combined-focused-and-targeted-quantitative-proteomics
#3
Mio Hirayama-Kurogi, Yohei Takizawa, Yasuto Kunii, Junya Matsumoto, Akira Wada, Mizuki Hino, Hiroyasu Akatsu, Yoshio Hashizume, Sakon Yamamoto, Takeshi Kondo, Shingo Ito, Masanori Tachikawa, Shin-Ichi Niwa, Hirooki Yabe, Tetsuya Terasaki, Mitsutoshi Setou, Sumio Ohtsuki
: Schizophrenia is a disabling mental illness associated with dysfunction of the prefrontal cortex, which affects cognition and emotion. The purpose of the present study was to identify altered molecular networks in the prefrontal cortex of schizophrenia patients by comparing protein expression levels in autopsied brains of patients and controls, using a combination of targeted and focused quantitative proteomics. We selected 125 molecules possibly related to schizophrenia for quantification by knowledge-based targeted proteomics...
February 15, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28214555/identification-of-a-fatty-acid-binding-protein4-ucp2-axis-regulating-microglial-mediated-neuroinflammation
#4
Cayla M Duffy, Hongliang Xu, Joshua P Nixon, David A Bernlohr, Tammy A Butterick
Hypothalamic inflammation contributes to metabolic dysregulation and the onset of obesity. Dietary saturated fats activate microglia via a nuclear factor-kappa B (NFκB) mediated pathway to release pro-inflammatory cytokines resulting in dysfunction or death of surrounding neurons. Fatty acid binding proteins (FABPs) are lipid chaperones regulating metabolic and inflammatory pathways in response to fatty acids. Loss of FABP4 in peripheral macrophages via either molecular or pharmacologic mechanisms results in reduced obesity-induced inflammation via a UCP2-redox based mechanism...
February 15, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28214532/smn1-functions-as-a-novel-inhibitor-for-traf6-mediated-nf-%C3%AE%C2%BAb-signaling
#5
Eun Kyung Kim, Eui-Ju Choi
Survival motor neuron (SMN) is a 38-kDa protein, whose deficiency in humans develops spinal muscular atrophy (SMA), an autosomal recessive neurodegenerative disease with muscular atrophy due to motor neuron death in the spinal cord. We now report that SMN prevents the activation of TRAF6 and IκB kinase (IKK) and thereby negatively regulates the NF-κB signaling processes. SMN physically interacted with TRAF6 and with each component of the IKK complex, IKK-α, IKK-β, and IKK-γ in BV2 microglia cells. Moreover, SMN1 inhibited the E3 ubiquitin ligase activity of TRAF6 as well as the kinase activity of IKK...
February 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28214522/prelimbic-cortex-extracellular-signal-regulated-kinase-1-2-activation-is-required-for-memory-retrieval-of-long-term-inhibitory-avoidance
#6
Fei Luo, Jian Zheng, Xuan Sun, Wei-Ke Deng, Fang Liu, Bao-Ming Li
Neural mechanism underlying memory retrieval has been extensively studied in the hippocampus and amygdala. However, little is known about the role of medial prefrontal cortex in long-term memory retrieval. We evaluate this issue in one-trial step-through inhibitory avoidance (IA) paradigm. Our results showed that, 1) inactivation of mPFC by local infusion of GABAA-receptor agonist muscimol caused severe deficits in retrieval of 1-day and 7-day but had no effects on 2-hour inhibitory avoidance memory; 2) the protein level of phosphorylated-ERK1/2 in mPFC were significantly increased following retrieval of 1-day and 7-day IA memory, so did the numbers of phosphorylated-ERK (pERK) and phosphorylated-CREB (pCREB) labeled neurons; 3) intra-mPFC infusion of ERK kinase inhibitor PD98095 significantly reduced phosphorylated ERK1/2 levels and phosphorylated-ERK1/2 and phosphorylated-CREB labeled cells, and severely impaired retrieval of 7-day IA memory when the drugs were administrated 30 min prior to test...
February 15, 2017: Brain Research
https://www.readbyqxmd.com/read/28214378/calcium-signaling-through-l-type-calcium-channels-role-in-pathophysiology-of-spinal-nociceptive-transmission
#7
REVIEW
Olivier Roca-Lapirot, Houda Radwani, Franck Aby, Frédéric Nagy, Marc Landry Pascal Fossat
L-type voltage-gated calcium channels (VGCCs) are ubiquitous channels in the central nervous system. L-type calcium channels (LTCs) are mostly post-synaptic channels regulating neuronal firing and gene expression. They play a role in important physio-pathological processes such as learning and memory, Parkinson's disease, autism and, as recognized more recently, in the pathophysiology of pain processes. Classically, the fundamental role of these channels in cardiovascular functions has limited the use of classical molecules to treat LTC-dependent disorders...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28214218/implication-of-downregulation-and-prospective-pathway-signaling-of-microrna-375-in-lung-squamous-cell-carcinoma
#8
Wen-Jie Chen, Ting-Qing Gan, Hui Qin, Su-Ning Huang, Li-Hua Yang, Ye-Ying Fang, Zu-Yun Li, Lin-Jiang Pan, Gang Chen
BACKGROUND: Lung cancer is one of the most typical cancers in the world. Altered expression profiles of microRNA-375(miR-375) are linked to many diseases including lung cancer. However, the relationship between miR-375 and lung squamous cell carcinoma (LUSC) is controversial. METHODS: We first evaluated the 23 LUSCs and the paired normal lung tissues by qRT-PCR. Then we analyzed the LUSC samples with miR-375 expression based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)...
January 22, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28213613/an-atf4-atg5-signaling-in-hypothalamic-pomc-neurons-regulates-fat-mass-via-affecting-energy-expenditure
#9
Yuzhong Xiao, Yalan Deng, Feixiang Yuan, Tingting Xia, Hao Liu, Zhigang Li, Zhixue Liu, Hao Ying, Yi Liu, Qiwei Zhai, Shanghai Chen, Feifan Guo
Although many biological functions of activating transcription factor 4 (ATF4) have been identified, a role of hypothalamic ATF4 in the regulation of energy homeostasis is poorly understood. Here, we showed that hypothalamic pro-opiomelanocortin (POMC) neurons specific ATF4 knockout (PAKO) mice are lean and have higher energy expenditure. Furthermore, PAKO mice were resistant to high-fat diet (HFD)-induced obesity, glucose intolerance and leptin resistance. Moreover, the expression of autophagy protein 5 (ATG5) was increased or decreased by ATF4 knockdown or over-expression, respectively, and ATF4 inhibited the transcription of ATG5 by binding to the basic zipper-containing protein (bZIP) sites on its promoter...
February 17, 2017: Diabetes
https://www.readbyqxmd.com/read/28213524/g-protein-coupled-receptor-kinase-2-grk-2-regulates-serotonin-metabolism-through-the-monoamine-oxidase-amx-2-in-caenorhabditis-elegans
#10
Jianjun Wang, Jiansong Luo, Dipendra K Aryal, William C Wetzel, Richard Nass, Jeffrey L Benovic
G protein-coupled receptors (GPCRs) regulate many animal behaviors. GPCR signaling is mediated by agonist-promoted interactions of GPCRs with heterotrimeric G proteins, GPCR kinases (GRKs) and arrestins. To further elucidate the role of GRKs in regulating GPCR-mediated behaviors, we utilized the genetic model system Caenorhabditis elegans. Our studies demonstrate that grk-2 loss-of-function strains are egg-laying defective and contain low levels of serotonin (5-HT) and high levels of the 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA)...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213521/signalling-adaptor-shcd-suppresses-erk-phosphorylation-distal-to-the-ret-and-trk-neurotrophic-receptors
#11
Melanie K B Wills, Ava Keyvani Chahi, Hayley R Lau, Manali Tilak, Brianna Guild, Laura A New, Peihua Lu, Keévin Jacquet, Susan O Meakin, Nicolas Bisson, Nina Jones
Proteins of the Shc family are typically involved in signal transduction events involving Ras/MAPK and PI3K/Akt pathways. In the nervous system, they function proximal to the neurotrophic factors that regulate cell survival, differentiation, and neuron-specific characteristics. The least-characterized homolog, ShcD, is robustly expressed in the developing and mature nervous system, but its contributions to neural cell circuitry are largely uncharted. We now report that ShcD binds to active Ret, TrkA, and TrkB neurotrophic factor receptors predominantly via its phosphotyrosine binding (PTB) domain...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213516/rapid-regulation-of-sialidase-activity-in-response-to-neural-activity-and-sialic-acid-removal-during-memory-processing-in-rat-hippocampus
#12
Akira Minami, Yuko Meguro, Sayaka Ishibashi, Ami Ishii, Mako Shiratori, Saki Sai, Yuuki Horii, Hirotaka Shimizu, Hokuto Fukumoto, Sumika Shinba, Risa Taguchi, Tadanobu Takahashi, Tadamune Otsubo, Kiyoshi Ikeda, Takashi Suzuki
Sialidase cleaves sialic acids on the extracellular cell surface as well as inside the cell, and is necessary for normal long-term potentiation (LTP) at MF-CA3 pyramidal cell synapses and for hippocampus-dependent spatial memory. Here, we investigated in detail the role of sialidase in memory processing. Sialidase activity measured with 4MU-Neu5Ac or X-Neu5Ac and FRV LB was increased by high K(+)-induced membrane depolarization. Sialidase activity was also increased by chemical LTP induction with forskolin and activation of BDNF signaling, non-NMDARs or NMDARs...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213446/acetylcholine-release-in-prefrontal-cortex-promotes-gamma-oscillations-and-theta-gamma-coupling-during-cue-detection
#13
W M Howe, H J Gritton, N Lusk, Erik A Roberts, Vaughn L Hetrick, Joshua D Berke, Martin Sarter
The capacity for using external cues to guide behavior ("cue detection") constitutes an essential aspect of attention and goal-directed behavior. The cortical cholinergic input system, via phasic increases in prefrontal acetylcholine release, plays an essential role in attention by mediating such cue detection. However, the relationship between cholinergic signaling during cue detection and neural activity dynamics in prefrontal networks remains unclear. Here we combined sub-second measures of cholinergic signaling, neurophysiological recordings, and cholinergic receptor blockade to delineate the cholinergic contributions to prefrontal oscillations during cue detection in rats...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28213159/signal-transduction-cascades-in-axon-regeneration-insights-from-c-elegans
#14
REVIEW
Naoki Hisamoto, Kunihiro Matsumoto
Axon regeneration after nerve injury is a conserved biological process in many animals, including humans. The nematode Caenorhabditis elegans (C. elegans) has recently emerged as a genetically tractable model for studying regenerative responses in neurons. Extensive studies over several years using this organism have revealed a number of intrinsic and extrinsic signal transduction cascades that regulate axon regeneration, and these are found to be conserved from worms to humans. Further studies have demonstrated that these cascades consist of several signaling networks that ultimately merge into the c-Jun N-terminal kinase (JNK) cascade...
February 14, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28212867/protective-effect-of-spermine-against-pentylenetetrazole-kindling-epilepsy-induced-comorbidities-in-mice
#15
Mandeep Kumar, Puneet Kumar
Nitric oxide (NO), an important intracellular signaling molecule is involved in modulation of neuronal transmission. The NO level increases during epileptic activity in animal models of epilepsy. However, its role in epileptic activity remains controversial. Spermine is an endogenous polyamine; possesses anti-oxidant property and has ability to modulate ion channels and NO synthase activity. Therefore, the present study was designed to investigate the role of NO pathway in the neuroprotective effect of spermine, in Pentylenetetrazol (PTZ) induced kindling epilepsy in mice...
February 14, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28212416/the-variability-of-multisensory-processes-of-natural-stimuli-in-human-and-non-human-primates-in-a-detection-task
#16
Cécile Juan, Céline Cappe, Baptiste Alric, Benoit Roby, Sophie Gilardeau, Pascal Barone, Pascal Girard
BACKGROUND: Behavioral studies in both human and animals generally converge to the dogma that multisensory integration improves reaction times (RTs) in comparison to unimodal stimulation. These multisensory effects depend on diverse conditions among which the most studied were the spatial and temporal congruences. Further, most of the studies are using relatively simple stimuli while in everyday life, we are confronted to a large variety of complex stimulations constantly changing our attentional focus over time, a modality switch that can impact on stimuli detection...
2017: PloS One
https://www.readbyqxmd.com/read/28212331/analysis-of-epidermal-growth-factor-receptor-related-gene-expression-changes-in-a-cellular-and-animal-model-of-parkinson-s-disease
#17
In-Su Kim, Sushruta Koppula, Shin-Young Park, Dong-Kug Choi
We employed transcriptome analysis of epidermal growth factor receptor related gene expression changes in cellular and animal models of Parkinson's disease (PD). We used a well-known Parkinsonian toxin 1-methyl-4-phenylpyridine (MPP⁺) to induce neuronal apoptosis in the human neuroblastoma SH-SY5Y cell line. The MPP⁺-treatment of SH-SY5Y cells was capable of inducing neuro-apoptosis, but it remains unclear what kinds of transcriptional genes are affected by MPP⁺ toxicity. Therefore the pathways that were significantly perturbed in MPP⁺ treated human neuroblastoma SH-SY5Y cells were identified based on genome-wide gene expression data at two time points (24 and 48 h)...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212107/rheb-in-neuronal-degeneration-regeneration-and-connectivity
#18
Veena Nambiar Potheraveedu, Miriam Schöpel, Raphael Stoll, Rolf Heumann
The small GTPase Rheb was originally detected as an immediate early response protein whose expression was induced by NMDA-dependent synaptic activity in the brain. Rheb's activity is highly regulated by its GTPase activating protein (GAP), the tuberous sclerosis complex protein, which stimulates the conversion from the active, GTP-loaded into the inactive, GDP-loaded conformation. Rheb has been established as an evolutionarily conserved molecular switch protein regulating cellular growth, cell volume, cell cycle, autophagy, and amino acid uptake...
February 17, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28211874/datf4-regulation-of-mitochondrial-folate-mediated-one-carbon-metabolism-is-neuroprotective
#19
Ivana Celardo, Susann Lehmann, Ana C Costa, Samantha Hy Loh, L Miguel Martins
Neurons rely on mitochondria as their preferred source of energy. Mutations in PINK1 and PARKIN cause neuronal death in early-onset Parkinson's disease (PD), thought to be due to mitochondrial dysfunction. In Drosophila pink1 and parkin mutants, mitochondrial defects lead to the compensatory upregulation of the mitochondrial one-carbon cycle metabolism genes by an unknown mechanism. Here we uncover that this branch is triggered by the activating transcription factor 4 (ATF4). We show that ATF4 regulates the expression of one-carbon metabolism genes SHMT2 and NMDMC as a protective response to mitochondrial toxicity...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28211790/flpstop-a-tool-for-conditional-gene-control-in-drosophila
#20
Yvette Erica Fisher, Helen H Yang, Jesse Isaacman-Beck, Marjorie Xie, Daryl M Gohl, Thomas R Clandinin
Manipulating gene function cell type-specifically is a common experimental goal in Drosophila research and has been central to studies of neural development, circuit computation, and behavior. However, current cell type-specific gene disruption techniques in flies often reduce gene activity incompletely or rely on cell division. Here we describe FlpStop, a generalizable tool for conditional gene disruption and rescue in post-mitotic cells. In proof-of-principle experiments, we manipulated apterous, a regulator of wing development...
February 17, 2017: ELife
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