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https://www.readbyqxmd.com/read/30316051/mir-125b-promotes-tau-phosphorylation-by-targeting-the-neural-cell-adhesion-molecule-in-neuropathological-progression
#1
Linyu Zhang, Hao Dong, Youwen Si, Nan Wu, Hao Cao, Bing Mei, Bo Meng
MicroRNAs, small noncoding RNAs, not only regulate gene expression at the post-transcriptional level in a variety of physiological processes but also accompany the initiation and progression of a vast number of diseases, including dementia. While miR-125b has been shown to be aberrantly expressed in some dementia patients, its role in the pathological process remains ambiguous. Presenilin-1/2 conditional double knockout mice exhibit a range of symptoms, including impaired cognition and memory, increased tau phosphorylation, neuroinflammation, and apoptosis, and are therefore regarded as a useful dementia model...
September 18, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/30316025/development-of-an-innervated-tissue-engineered-skin-with-human-sensory-neurons-and-schwann-cells-differentiated-from-ips-cells
#2
Quentin Muller, Marie-Josée Beaudet, Thiéry De Serres-Bérard, Sabrina Bellenfant, Vincent Flacher, François Berthod
Cutaneous innervation is increasingly recognized as a major element of skin physiopathology through the neurogenic inflammation driven by neuropeptides that are sensed by endothelial cells and the immune system. To investigate this process in vitro, models of innervated tissue-engineered skin (TES) were developed, yet exclusively with murine sensory neurons extracted from dorsal root ganglions. In order to build a fully human model of innervated TES, we used induced pluripotent stem cells (iPSC) generated from human skin fibroblasts...
October 10, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/30315937/peroxiredoxin-interaction-with-the-cytoskeletal-regulatory-protein-crmp2-investigation-of-a-putative-redox-relay
#3
Paul E Pace, Alexander V Peskin, Andreas Konigstorfer, Christine J Jasoni, Christine C Winterbourn, Mark B Hampton
Hydrogen peroxide (H2 O2 ) acts as a signaling molecule in cells by oxidising cysteine residues in regulatory proteins such as phosphatases, kinases and transcription factors. It is unclear exactly how many of these proteins are specifically targeted by H2 O2 because they appear too unreactive to be directly oxidised. One proposal is that peroxiredoxins (Prxs) initially react with H2 O2 and then oxidise adjacent proteins via a thiol relay mechanism. The aim of this study was to identify constitutive interaction partners of Prx2 in Jurkat T-lymphoma cells, in which thiol protein oxidation occurs at low micromolar concentrations of H2 O2 ...
October 10, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/30315936/angiotensin-ii-induces-oxidative-stress-and-upregulates-neuroprotective-signaling-from-the-nrf2-and-klf9-pathway-in-dopaminergic-cells
#4
Juan A Parga, Ana I Rodriguez-Perez, Maria Garcia-Garrote, Jannette Rodriguez-Pallares, Jose L Labandeira-Garcia
Nuclear factor-E2-related factor 2 (NRF2) is a transcription factor that activates the antioxidant cellular defense in response to oxidative stress, leading to neuroprotective effects in Parkinson's disease (PD) models. We have previously shown that Angiotensin II (AngII) induces an increase in reactive oxygen species (ROS) via AngII receptor type 1 and NADPH oxidase (NOX), which may activate the NRF2 pathway. However, controversial data suggest that AngII induces a decrease in NRF2 signaling leading to an increase in oxidative stress...
October 10, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/30315929/microglial-overexpression-of-fals-linked-mutant-sod1-induces-sod1-processing-impairment-activation-and-neurotoxicity-and-is-counteracted-by-the-autophagy-inducer-trehalose
#5
Francesca Massenzio, Emiliano Peña-Altamira, Sabrina Petralla, Marco Virgili, Giampaolo Zuccheri, Andrea Miti, Elisabetta Polazzi, Ilaria Mengoni, Deborah Piffaretti, Barbara Monti
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Mutations in the gene encoding copper/zinc superoxide dismutase-1 (SOD1) are responsible for most familiar cases, but the role of mutant SOD1 protein dysfunction in non-cell autonomous neurodegeneration, especially in relation to microglial activation, is still unclear. Here, we focused our study on microglial cells, which release SOD1 also through exosomes. We observed that in rat primary microglia the overexpression of the most-common SOD1 mutations linked to fALS (G93A and A4V) leads to SOD1 intracellular accumulation, which correlates to autophagy dysfunction and microglial activation...
October 10, 2018: Biochimica et biophysica acta. Molecular basis of disease
https://www.readbyqxmd.com/read/30315878/altered-expression-of-phox2-transcription-factors-in-the-locus-coeruleus-in-major-depressive-disorder-mimicked-by-chronic-stress-and-corticosterone-treatment-in-vivo-and-in-vitro
#6
Yan Fan, Ping Chen, Muhammad U Raza, Attila Szebeni, Katalin Szebeni, Gregory A Ordway, Craig A Stockmeier, Meng-Yang Zhu
Phox2a and Phox2b are two homeodomain transcription factors playing a pivotal role in the development of noradrenergic neurons during the embryonic period. However, their expression and function in adulthood remain to be elucidated. Using human postmortem brain tissues, rat stress models and cultured cells, this study aimed to examine the alteration of Phox2a and Phox2b expression. The results show that Phox2a and Phox2b are normally expressed in the human locus coeruleus (LC) in adulthood. Furthermore, the levels of Phox2a protein and mRNA and protein levels of Phox2b were significantly elevated in the LC of brain donors that suffered from the major depressive disorder, as compared to age-matched and psychiatrically normal control donors...
October 10, 2018: Neuroscience
https://www.readbyqxmd.com/read/30315829/neuroplastic-changes-in-the-olfactory-bulb-associated-with-nasal-inflammation-in-mice
#7
Sanae Hasegawa-Ishii, Atsuyoshi Shimada, Fumiaki Imamura
BACKGROUND: Rhinitis and rhinosinusitis are olfactory disorders caused by inflammation of the nasal passage and paranasal sinuses. Although chronic rhinosinusitis patients have smaller olfactory bulbs (OBs), there is limited knowledge regarding the influence of chronic nasal inflammation on OB neurons. OBJECTIVE: Repeated intranasal administration of lipopolysaccharide (LPS) that induced persistent nasal inflammation in mice caused a loss of olfactory sensory neurons (OSNs) and gliosis and synaptic loss in the OB within three weeks...
October 10, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/30315808/astrocyte-specific-deletion-of-kir6-1-k-atp-channel-aggravates-cerebral-ischemia-reperfusion-injury-through-endoplasmic-reticulum-stress-in-mice
#8
Chong-Jin Zhong, Miao-Miao Chen, Ming Lu, Jian-Hua Ding, Ren-Hong Du, Gang Hu
ATP-sensitive potassium (K-ATP) channels, coupling cell metabolism to cell membrane potential, are involved in brain diseases including stroke. Emerging evidence shows that astrocytes play important roles in the pathophysiology of cerebral ischemia. Kir6.1, a pore-forming subunit of K-ATP channel, is prominently expressed in astrocytes and participates in regulating its function. However, the exact role of astrocytic Kir6.1-containg K-ATP channel (Kir6.1/K-ATP) in ischemic stroke remains unclear. Here, we found that astrocytic Kir6...
October 10, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/30315761/preparation-of-stable-tau-oligomers-for-cellular-and-biochemical-studies
#9
Thomas K Karikari, David A Nagel, Alastair Grainger, Charlotte Clarke-Bland, Eric J Hill, Kevin G Moffat
Increasing evidence suggests that small oligomers are the principal neurotoxic species of tau in Alzheimer's disease and other tauopathies. However, mechanisms of tau oligomer-mediated neurodegeneration are poorly understood. The transience of oligomers due to aggregation can compromise the stability of oligomers prepared in vitro. Consequently, we sought to develop an efficient method which maintains the stability and globular conformation of preformed oligomers. This study demonstrates that labeling a single-cysteine form of the pro-aggregant tau four-repeat region (K18) with either Alexa Fluor 488-C5-maleimide or N-ethylmaleimide in reducing conditions stabilizes oligomers by impeding their further aggregation...
October 10, 2018: Analytical Biochemistry
https://www.readbyqxmd.com/read/30315732/fabrication-of-thin-layer-matrigel-based-constructs-for-3d-cell-culture
#10
Kristin Robin Ko, Meng-Chiao Tsai, John P Frampton
Extracellular matrix-based hydrogels such as Matrigel are easy-to-use, commercially available, and offer environments for three-dimensional (3D) cell culture that mimic native tissue. However, manipulating small volumes of these materials to produce thin-layer 3D culture systems suitable for analysis is difficult due to air-liquid-substrate interfacial tension effects and evaporation. Here, we demonstrate two simple techniques that use standard liquid-handling tools and non-treated 96-well plates to produce uniform, thin-layer constructs for 3D culture of cells in Matrigel...
October 13, 2018: Biotechnology Progress
https://www.readbyqxmd.com/read/30315688/5-hydroxytryptamine-and-dopamine-neurons-in-the-cerebellum-of-the-new-hatching-yangtze-alligator-alligator-sinensis
#11
Shijia Ren, Meifang Chen, Lanying Yang, Zaiqun Liu
Nissl and immunohistochemical staining methods were used to morphologically characterize the cerebellum of the new-hatching Yangtze alligator, and the cerebellar histological structure and the distribution profiles of 5-hydroxytryptamine (5-HT) and dopamine (DA) neurons were investigated for the first time. The results of cerebellar histological structure showed that there was a ventriculus cerebelli in the cerebellum of the new-hatching Yangtze alligator, the surface of the cerebellar cortex was not very smooth, the cerebellar cortex could be divided into four layers which include external granular layer, molecular layer, Purkinje cell layer and granular layer, Purkinje cell layer could be characterized specially by multilayer, two cerebellar nuclei termed as the nucleus cerebelli lateralis and the nucleus cerebelli medialis were found in the cerebellar medulla...
October 13, 2018: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/30315630/adenosine-a-1-receptor-mrna-expression-by-neurons-and-glia-in-the-auditory-forebrain
#12
Troy A Hackett
In the brain, purines such as ATP and adenosine can function as neurotransmitters and co-transmitters, or serve as signals in neuron-glial interactions. In thalamocortical (TC) projections to sensory cortex, adenosine functions as a negative regulator of glutamate release via activation of the presynaptic adenosine A1 receptor (A1 R). In the auditory forebrain, restriction of A1 R-adenosine signaling in medial geniculate (MG) neurons is sufficient to extend LTP, LTD, and tonotopic map plasticity in adult mice for months beyond the critical period...
October 12, 2018: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/30315526/catalpol-inhibits-homocysteine-induced-oxidation-and-inflammation-via-inhibiting-nox4-nf-%C3%AE%C2%BAb-and-grp78-perk-pathways-in-human-aorta-endothelial-cells
#13
Huimin Hu, Changyuan Wang, Yue Jin, Qiang Meng, Qi Liu, Zhihao Liu, Kexin Liu, Xiaoyu Liu, Huijun Sun
Hyperhomocysteinemia (HHCY) has been recognized as an independent risk factor for atherosclerosis and plays a vital role in the development of atherosclerosis. Catalpol, an iridoid glucoside extracted from the root of Rehmannia glutinosa, can produce anti-inflammatory, anti-oxidant, anti-tumor, and dopaminergic neurons protecting effects. This study aimed to determine the protecting effects of catalpol against homocysteine (HCY)-induced injuries in human aortic endothelial cells (HAECs) and uncover the underlying mechanisms: 1...
October 12, 2018: Inflammation
https://www.readbyqxmd.com/read/30315479/bezafibrate-upregulates-mitochondrial-biogenesis-and-influence-neural-differentiation-of-human-induced-pluripotent-stem-cells
#14
Justyna Augustyniak, Jacek Lenart, Paweł Gaj, Monika Kolanowska, Krystian Jazdzewski, Piotr Pawel Stepien, Leonora Buzanska
Bezafibrate (BZ) regulates mitochondrial biogenesis by activation of PPAR's receptors and enhancing the level of PGC-1α coactivator. In this report, we investigated the effect of BZ on the expression of genes (1) that are linked to different pathways involved in mitochondrial biogenesis, e.g., regulated by PPAR's receptors or PGC-1α coactivator, and (2) involved in neuronal or astroglial fate, during neural differentiation of hiPSC. The tested cell populations included hiPSC-derived neural stem cells (NSC), early neural progenitors (eNP), and neural progenitors (NP)...
October 13, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30315453/aluminum-induced-neural-cell-death
#15
Qinli Zhang
Aluminum (Al), an abundant element in the earth's crust, is well-known for its neurotoxicity. Nonetheless, its causal role in neurodegenerative diseases, particularly in Alzheimer's disease (AD), is still in debate. Ample studies have shown that neural cell death and cognitive deficits induced by Al are similar to those in AD. In the present chapter, we demonstrate separately the Al-induced cell death in neuron, neuroglia cells, and co-cultured neural cells from newborn rats to illustrate the neurotoxic effects...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/30315404/brain-ceruloplasmin-expression-after-experimental-intracerebral-hemorrhage-and-protection-against-iron-induced-brain-injury
#16
Hongwei Liu, Ya Hua, Richard F Keep, Guohua Xi
Ceruloplasmin (CP) is an essential ferroxidase that is involved in maintaining iron homeostasis by oxidizing toxic ferrous iron (Fe2+ ) to less-toxic ferric iron (Fe3+ ). CP has been well studied in many neurodegenerative diseases, but there has not been an in-depth investigation in intracerebral hemorrhage (ICH). This research investigated brain CP expression in rats after ICH and the effect of CP on Fe2+ -induced brain injury. This study had two parts: first, rats had injection of autologous blood into the right basal ganglia and the time course of CP expression in the brain examined (protein and mRNA)...
October 12, 2018: Translational Stroke Research
https://www.readbyqxmd.com/read/30315388/systemic-inflammation-impairs-proliferation-of-hippocampal-type-2-intermediate-precursor-cells
#17
Marlene Sinai Melo-Salas, Martha Pérez-Domínguez, Angélica Zepeda
Neurogenesis is a plastic event modulated by external cues. Systemic inflammation decreases neurogenesis in the dentate gyrus (DG) in part through the proliferative restrain of neural precursor cells (NPCs). To evaluate if inflammation affects the cell cycle progression of particular populations of NPCs, we treated young-adult mice with a single i.p. injection of saline or 1 mg/kg LPS. After 7 days, we analysed proliferation of new BrdU+/DCX+ cells through immunohistochemistry. We extracted the hippocampus and performed a neurosphere assay and a flow cytometric analysis to evaluate proliferation and to identify the phase of the cell cycle in specific populations of DG-derived NPCs...
October 12, 2018: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/30315249/identification-and-characterization-of-a-series-of-novel-hcn-channel-inhibitors
#18
Shu-Jun Chen, Yao Xu, Ye-Mei Liang, Ying Cao, Jin-Yan Lv, Jian-Xin Pang, Ping-Zheng Zhou
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a critical role in controlling pacemaker activity in both heart and nervous system. Developing HCN channel inhibitors has been proposed to be an important strategy for the treatment of pain, heart failure, arrhythmias, and epilepsy. One HCN channel inhibitor, ivabradine, has been clinically approved for the treatment of angina pectoris and heart failure. In this study, we designed and synthesized eight alkanol amine derivatives, and assessed their effects on HCN channels expressed in COS7 cells using a whole-cell patch clamp method...
October 12, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/30315245/a-dimeric-fluorescent-protein-yields-a-bright-red-shifted-gevi-capable-of-population-signals-in-brain-slice
#19
Bumjun Yi, Bok Eum Kang, Sungmoo Lee, Sophie Braubach, Bradley J Baker
A bright, red-shifted Genetically Encoded Voltage Indicator (GEVI) was developed using a modified version of the fluorescent protein, tdTomato. Dimerization of the fluorescent domain for ArcLight-type GEVIs has been shown to affect the signal size of the voltage-dependent optical signal. For red-shifted GEVI development, tdTomato was split fusing a single dTomato chromophore to the voltage sensing domain. Optimization of the amino acid length and charge composition of the linker region between the voltage sensing domain and the fluorescent protein resulted in a probe that is an order of magnitude brighter than FlicR1 at a resting potential of -70 mV and exhibits a ten-fold larger change in fluorescence (ΔF) upon 100 mV depolarization of the plasma membrane in HEK 293 cells...
October 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30315166/an-expression-atlas-of-variant-ionotropic-glutamate-receptors-identifies-a-molecular-basis-of-carbonation-sensing
#20
Juan Antonio Sánchez-Alcañiz, Ana Florencia Silbering, Vincent Croset, Giovanna Zappia, Anantha Krishna Sivasubramaniam, Liliane Abuin, Saumya Yashmohini Sahai, Daniel Münch, Kathrin Steck, Thomas O Auer, Steeve Cruchet, G Larisa Neagu-Maier, Simon G Sprecher, Carlos Ribeiro, Nilay Yapici, Richard Benton
Through analysis of the Drosophila ionotropic receptors (IRs), a family of variant ionotropic glutamate receptors, we reveal that most IRs are expressed in peripheral neuron populations in diverse gustatory organs in larvae and adults. We characterise IR56d, which defines two anatomically-distinct neuron classes in the proboscis: one responds to carbonated solutions and fatty acids while the other represents a subset of sugar- and fatty acid-sensing cells. Mutational analysis indicates that IR56d, together with the broadly-expressed co-receptors IR25a and IR76b, is essential for physiological responses to carbonation and fatty acids, but not sugars...
October 12, 2018: Nature Communications
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