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Molecular Neurobiology

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https://www.readbyqxmd.com/read/29143288/gsk3%C3%AE-controls-mtor-and-prosurvival-signaling-in-neurons
#1
Malgorzata Urbanska, Agata Gozdz, Matylda Macias, Iwona A Cymerman, Ewa Liszewska, Ilona Kondratiuk, Herman Devijver, Benoit Lechat, Fred Van Leuven, Jacek Jaworski
Glycogen synthase kinases-3β (GSK3β) is a key regulator of cell homeostasis. In neurons, GSK3β contributes to control of neuronal transmission and plasticity. Despite extensive studies in non-neuronal cells, crosstalk between GSK3β and other signaling pathways remains not well defined in neurons. In the present study, we report that GSK3β positively affected the activity of effectors of mammalian target of rapamycin complex 1 (mTORC1) and complex 2 (mTORC2), in mature neurons in vitro and in vivo. GSK3β also promoted prosurvival signaling and attenuated kainic acid-induced apoptosis...
November 15, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29143287/lipoic-acid-stimulates-camp-production-in-healthy-control-and-secondary-progressive-ms-subjects
#2
Sarah E Fiedler, Vijayshree Yadav, Amelia R Kerns, Catherine Tsang, Sheila Markwardt, Edward Kim, Rebecca Spain, Dennis Bourdette, Sonemany Salinthone
Lipoic acid (LA) exhibits antioxidant and anti-inflammatory properties; supplementation reduces disease severity and T lymphocyte migration into the central nervous system in a murine model of multiple sclerosis (MS), and administration in secondary progressive MS (SPMS) subjects reduces brain atrophy compared to placebo. The mechanism of action (MOA) of LA's efficacy in suppression of MS pathology is incompletely understood. LA stimulates production of the immunomodulator cyclic AMP (cAMP) in vitro. To determine whether cAMP could be involved in the MOA of LA in vivo, we performed a clinical trial to examine whether LA stimulates cAMP production in healthy control and MS subjects, and whether there are differences in the bioavailability of LA between groups...
November 15, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29134515/neuroprotective-potential-and-paracrine-activity-of-stromal-vs-culture-expanded-hmsc-derived-from-wharton-jelly-under-co-cultured-with-hippocampal-organotypic-slices
#3
Sylwia Dabrowska, Joanna Sypecka, Anna Jablonska, Lukasz Strojek, Miroslaw Wielgos, Krystyna Domanska-Janik, Anna Sarnowska
Regardless of enormous translational progress in stem cell clinical application, our knowledge about biological determinants of transplantation-related protection is still limited. In addition to adequate selection of the cell source well dedicated to a specific disease and optimal standardization of all other pre-transplant procedures, we have decided to focus more attention to the impact of culture time and environment itself on molecular properties and regenerative capacity of cell cultured in vitro. The aim of this investigation was to determine neuroprotection-linked cell phenotypic and functional changes that could spontaneously take place when freshly isolated Wharton's jelly mesenchymal stem cell (WJ-MSC) undergo standard selection, growth, and spontaneous differentiation throughout passaging in vitro...
November 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29134514/expression-of-bc1-impairs-spatial-learning-and-memory-in-alzheimer-s-disease-via-app-translation
#4
Tongmei Zhang, Pei Pang, Zemin Fang, Yu Guo, Hao Li, Xinyan Li, Tian Tian, Xin Yang, Wenting Chen, Shu Shu, Na Tang, Jianhua Wu, Houze Zhu, Lei Pei, Dan Liu, Qing Tian, Jian Wang, Lin Wang, Ling-Qiang Zhu, Youming Lu
Aggregation of amyloid-β (Aβ) peptides, which are the cleavage products of amyloid precursor protein (APP), is a major pathological hallmark in the brain of Alzheimer's disease (AD). Now, we know little about the roles of APP translation in the disease progression of AD. Here, we show that BC1, a long noncoding RNA (lncRNA), is expressed in the brain of AD mice. BC1 induces APP mRNA translation via association with a fragile X syndrome protein (FMRP). Inhibition of BC1 or BC1-FMRP association in AD mice blocks aggregation of Aβ in the brain and protects against the spatial learning and memory deficits...
November 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29128907/a-new-conditionally-immortalized-human-fetal-brain-pericyte-cell-line-establishment-and-functional-characterization-as-a-promising-tool-for-human-brain-pericyte-studies
#5
Kenta Umehara, Yuchen Sun, Satoshi Hiura, Koki Hamada, Motoyuki Itoh, Keita Kitamura, Motohiko Oshima, Atsushi Iwama, Kosuke Saito, Naohiko Anzai, Kan Chiba, Hidetaka Akita, Tomomi Furihata
While pericytes wrap around microvascular endothelial cells throughout the human body, their highest coverage rate is found in the brain. Brain pericytes actively contribute to various brain functions, including the development and stabilization of the blood-brain barrier (BBB), tissue regeneration, and brain inflammation. Accordingly, detailed characterization of the functional nature of brain pericytes is important for understanding the mechanistic basis of brain physiology and pathophysiology. Herein, we report on the development of a new human brain pericyte cell line, hereafter referred to as the human brain pericyte/conditionally immortalized clone 37 (HBPC/ci37)...
November 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29128906/toll-like-receptor-3-mediates-hiv-1-induced-interleukin-6-expression-in-the-human-brain-endothelium-via-tak1-and-jnk-pathways-implications-for-viral-neuropathogenesis
#6
Biju Bhargavan, Georgette D Kanmogne
HIV-1-associated neurocognitive disorders (HAND) is associated with blood-brain-barrier (BBB) inflammation, and inflammation involves toll-like receptors (TLRs) signaling. It is not known whether primary human brain microvascular endothelial cells (HBMEC), the major BBB component, express TLRs or whether TLRs are involved in BBB dysfunction and HAND. We demonstrate that HBMEC express TLR3, 4, 5, 7, 9, and 10, and TLR3 was the most abundant. HIV-1 and TLR3 activation increased endothelial TLR3 transcription and expression...
November 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29128905/down-syndrome-ipsc-derived-astrocytes-impair-neuronal-synaptogenesis-and-the-mtor-pathway-in-vitro
#7
Bruno H S Araujo, Carolini Kaid, Janaina S De Souza, Sérgio Gomes da Silva, Ernesto Goulart, Luiz C J Caires, Camila M Musso, Laila B Torres, Adriano Ferrasa, Roberto Herai, Mayana Zatz, Oswaldo K Okamoto, Esper A Cavalheiro
Several methods have been used to study the neuropathogenesis of Down syndrome (DS), such as mouse aneuploidies, post mortem human brains, and in vitro cell culture of neural progenitor cells. More recently, induced pluripotent stem cell (iPSC) technology has offered new approaches in investigation, providing a valuable tool for studying specific cell types affected by DS, especially neurons and astrocytes. Here, we investigated the role of astrocytes in DS developmental disease and the impact of the astrocyte secretome in neuron mTOR signaling and synapse formation using iPSC derived from DS and wild-type (WT) subjects...
November 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29128904/pharmacological-rescue-of-hippocampal-fear-learning-deficits-in-fragile-x-syndrome
#8
Luis A Martinez, Maria Victoria Tejada-Simon
Fragile X Syndrome (FXS) is the leading cause of autism spectrum disorder and intellectual disability and results from loss of Fragile X mental retardation protein (FMRP). In neurons, FMRP controls the translation of synaptic plasticity proteins that are implicated in learning and memory. FMRP also regulates development- and experience-dependent actin cytoskeleton remodeling within dendritic spines through the small Rho GTPase Rac1. Modulation of Rac1 activity is critical during synaptic plasticity as well as learning and memory...
November 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29128903/impairment-of-thiamine-transport-at-the-gut-bbb-axis-contributes-to-wernicke-s-encephalopathy
#9
P M Abdul-Muneer, Saleena Alikunju, Heather Schuetz, Adam M Szlachetka, Xiaotang Ma, James Haorah
Wernicke's encephalopathy, a common neurological disease, is caused by thiamine (vitamin B1) deficiency. Neuropathy resulting from thiamine deficiency is a hallmark of Wernicke-Korsakoff syndrome in chronic alcohol users. The underlying mechanisms of this deficiency and progression of neuropathy remain to be understood. To uncover the unknown mechanisms of thiamine deficiency in alcohol abuse, we used chronic alcohol consumption or thiamine deficiency diet ingestion in animal models. Observations from animal models were validated in primary human neuronal culture for neurodegenerative process...
November 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29128902/overexpression-of-5-lipoxygenase-worsens-the-phenotype-of-a-mouse-model-of-tauopathy
#10
Phillip F Giannopoulos, Domenico Praticò
Brain accumulation of increasing amount of phosphorylated microtubule associated tau protein is one the major hallmark lesions of Alzheimer's disease (AD) and related tauopathies. Consistent evidence from clinical and animal studies has shown that neuroinflammation characterizes these diseases. The 5-lipoxygenase (5LO) is an enzyme protein whose metabolic products are lipids with potent inflammatory actions. Previously, we showed that blockade of 5LO activation ameliorates the phenotype of the htau transgenic mice...
November 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29119536/turning-death-to-growth-hematopoietic-growth-factors-promote-neurite-outgrowth-through-mek-erk-p53-pathway
#11
Mei Gao, Li-Ru Zhao
Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are the essential hematopoietic growth factors to control hematopoiesis. However, the role of SCF and G-CSF in the central nervous system remains poorly understood. Here, we have demonstrated the involvement of MEK/ERK/p53 signaling in SCF + G-CSF-enhanced neurite extension. Cortical neurons dissected from embryonic rat brains were seeded onto the membranes of transwell inserts, and neurite outgrowth was determined by using both the neurite outgrowth quantification assay kit and immunostaining of β III tubulin...
November 8, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29119535/mitochondria-bound-hexokinase-mt-hk-activity-differ-in-cortical-and-hypothalamic-synaptosomes-differential-role-of-mt-hk-in-h2o2-depuration
#12
João Paulo Cavalcanti-de-Albuquerque, Eduardo de Souza Ferreira, Denise Pires de Carvalho, Antonio Galina
Glucose and oxygen are vital for the brain, as these molecules provide energy and metabolic intermediates that are necessary for cell function. The glycolysis pathway and mitochondria play a pivotal role in cell energy metabolism, which is closely related to reactive oxygen species (ROS) production. Hexokinase (HK) is a key enzyme involved in glucose metabolism that modulates the level of brain mitochondrial ROS by recycling ADP for oxidative phosphorylation (OxPhos). Here, we hypothesize that the control of mitochondrial metabolism by hexokinase differs in distinct areas of the brain, such as the cortex and hypothalamus, in which ROS might function as signaling molecules...
November 8, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29119534/angiotensin-ii-causes-neuronal-damage-in-stretch-injured-neurons-protective-effects-of-losartan-an-angiotensin-t1-receptor-blocker
#13
P M Abdul-Muneer, Saurav Bhowmick, Nicholas Briski
Angiotensin II (Ang II) is a mediator of oxidative stress via activation/induction of reactive oxygen and nitrogen species-generating enzymes, NADPH oxidase (NOX) and inducible nitric oxide synthase (iNOS). We investigated the hypothesis that overproduction of Ang II during traumatic brain injury (TBI) induces the activation of the oxidative stress, which triggers neuroinflammation and cell apoptosis in a cell culture model of neuronal stretch injury. We first established that stretch injury causes a rapid increase in the level of Ang II, which causes the release of pro-inflammatory cytokines, IL-1β and TNF-α, via the induction of oxidative stress...
November 8, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29101647/plasma-mir-124-is-a-promising-candidate-biomarker-for-human-intracerebral-hemorrhage-stroke
#14
Zifeng Wang, Gang Lu, Johnny Sze, Yao Liu, Sheng Lin, Hong Yao, Ji Zhang, Dan Xie, Quentin Liu, Hsiang-Fu Kung, Marie Chia-Mi Lin, Wai Sang Poon
Stroke causes death or long-term disabilities and threatens the general health of the population worldwide. Recent studies have suggested that miRNAs are dysregulated and can be used as biomarkers for diagnosis and prognosis in stroke. The intracerebral hemorrhage (ICH) accounts for 15% of all the stroke cases. However, at present, little is known regarding the functions and clinical implications of miRNAs in ICH. In the present study, we established the collagenase-induced rat ICH model to mimic human ICH syndrome...
November 3, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29101646/s-adenosylmethionine-promotes-oxidative-stress-and-decreases-na-k-atpase-activity-in-cerebral-cortex-supernatants-of-adolescent-rats-implications-for-the-pathogenesis-of-s-adenosylhomocysteine-hydrolase-deficiency
#15
Ângela Zanatta, Cristiane Cecatto, Rafael Teixeira Ribeiro, Alexandre Umpierrez Amaral, Angela Ts Wyse, Guilhian Leipnitz, Moacir Wajner
S-Adenosylmethionine (AdoMet) concentrations are highly elevated in tissues and biological fluids of patients affected by S-adenosylhomocysteine hydrolase deficiency, who are clinically characterized by cerebral symptoms whose pathogenesis is still unknown. In the present work, we investigated the effects of AdoMet on redox homeostasis and on the activity of Na(+), K(+)-ATPase in the cerebral cortex of young rats. AdoMet caused lipid peroxidation (increase of malondialdehyde concentrations) and protein oxidation (increase of carbonyl formation and decrease of sulfhydryl content)...
November 3, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29086247/paracrine-and-intracrine-angiotensin-1-7-mas-receptor-axis-in-the-substantia-nigra-of-rodents-monkeys-and-humans
#16
Maria A Costa-Besada, Rita Valenzuela, Pablo Garrido-Gil, Begoña Villar-Cheda, Juan A Parga, Jose L Lanciego, Jose L Labandeira-Garcia
In addition to the classical hormonal (tissue-to-tissue) renin-angiotensin system (RAS), there are a paracrine (cell-to-cell) and an intracrine (intracellular/nuclear) RAS. A local paracrine brain RAS has been associated with several brain disorders, including Parkinson's disease (PD). Classically, angiotensin II (Ang II) is the main RAS effector peptide and acts through two major receptors: Ang II type 1 and 2 (AT1 and AT2) receptors. It has been shown that enhanced activation of the Ang II/AT1 axis exacerbates dopaminergic cell death...
October 30, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29086246/melatonin-prevents-the-harmful-effects-of-obesity-on-the-brain-including-at-the-behavioral-level
#17
Adrian Rubio-González, Juan Carlos Bermejo-Millo, Beatriz de Luxán-Delgado, Yaiza Potes, Zulema Pérez-Martínez, José Antonio Boga, Ignacio Vega-Naredo, Beatriz Caballero, Juan José Solano, Ana Coto-Montes
Obesity is a health problem caused by a diet rich in energy and the sedentary lifestyle of modern societies. A leptin deficiency is one of the worst causes of obesity, since it results in morbid obesity, a chronic disease without a cure. Leptin is an adipokine secreted in a manner dependent on the circadian rhythm that ultimately reduces food intake. We studied cellular alterations in brain of leptin-deficient obese animals and tested whether these alterations are reflected in abnormal behaviors. Obesity induced increases in oxidative stress and the unfolded protein response caused by endoplasmic reticulum stress...
October 30, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29079999/trafficking-in-alzheimer-s-disease-modulation-of-app-transport-and-processing-by-the-transmembrane-proteins-lrp1-sorla-sorcs1c-sortilin-and-calsyntenin
#18
REVIEW
Simone Eggert, Carolin Thomas, Stefan Kins, Guido Hermey
The amyloid precursor protein (APP), one key player in Alzheimer's disease (AD), is extensively processed by different proteases. This leads to the generation of diverging fragments including the amyloid β (Aβ) peptide, which accumulates in brains of AD patients. Subcellular trafficking of APP is an important aspect for its proteolytic conversion, since the various secretases which cleave APP are located in different cellular compartments. As a consequence, altered subcellular targeting of APP is thought to directly affect the degree to which Aβ is generated...
October 27, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29079998/role-of-3-acetyl-11-keto-beta-boswellic-acid-in-counteracting-lps-induced-neuroinflammation-via-modulation-of-mirna-155
#19
Aya Shoukry Sayed, Iman Emam Omar Gomaa, Michael Bader, Nesrine Salah El Dine El Sayed
Neuroinflammation is one of the most important mechanisms underlying neurodegeneration. Lipopolysaccharide (LPS) is a potent inflammogen which causes cognitive dysfunction. Boswellia serrata is known since many years as a powerful anti-inflammatory herbal drug. Its beneficial effect mainly arises from inhibition of 5-lipoxygenase (5-LO) enzyme. 3-acetyl-11-keto-β-boswellic acid (AKBA) is the most potent 5-LO inhibitor extracted from the oleo-gum-resin of Boswellia serrata. The aim of the present work is to study the molecular mechanisms underlying the anti-inflammatory and neuroprotective effects of AKBA and dexamethasone (DEX) in LPS-induced neuroinflammatory model...
October 27, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29079997/validation-of-reference-genes-for-expression-studies-in-human-meningiomas-under-different-experimental-settings
#20
Diana Freitag, Arend Koch, Aaron Lawson McLean, Rolf Kalff, Jan Walter
Quantitative polymerase chain reaction (qPCR) is a sensitive technique for the quantitative analysis of gene expression levels. To compare mRNA transcripts across tumour and non-pathological tissue, appropriate reference genes are required for internal standardisation. Validation of these reference genes in meningiomas has not yet been reported. After mRNA transcription of meningioma (WHO grade I-III) and meningeal tissue from three different experimental sample types (fresh tissue, primary cell cultures and FFPE tissue), 13 candidate reference genes (ACTB, B2M, HPRT, VIM, GAPDH, YWHAZ, EIF4A2, MUC1, ATP5B, GNB2L, TUBB, CYC1, RPL13A) were chosen for quantitative expression analysis...
October 27, 2017: Molecular Neurobiology
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