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Frontiers in Molecular Neuroscience

Ana Filošević, Sabina Al-Samarai, Rozi Andretić Waldowski
Drosophila melanogaster can be used to identify genes with novel functional roles in neuronal plasticity induced by repeated consumption of addictive drugs. Behavioral sensitization is a relatively simple behavioral output of plastic changes that occur in the brain after repeated exposures to drugs of abuse. The development of screening procedures for genes that control behavioral sensitization has stalled due to a lack of high-throughput behavioral tests that can be used in genetically tractable organism, such as Drosophila ...
2018: Frontiers in Molecular Neuroscience
Sophie Leacock, Parnayan Syed, Victoria M James, Anna Bode, Koichi Kawakami, Angelo Keramidas, Maximiliano Suster, Joseph W Lynch, Robert J Harvey
Inhibitory glycine receptors (GlyRs) are pentameric ligand-gated anion channels with major roles in startle disease/hyperekplexia (GlyR α1), cortical neuronal migration/autism spectrum disorder (GlyR α2), and inflammatory pain sensitization/rhythmic breathing (GlyR α3). However, the role of the GlyR α4 subunit has remained enigmatic, because the corresponding human gene ( GLRA4 ) is thought to be a pseudogene due to an in-frame stop codon at position 390 within the fourth membrane-spanning domain (M4). Despite this, a recent genetic study has implicated GLRA4 in intellectual disability, behavioral problems and craniofacial anomalies...
2018: Frontiers in Molecular Neuroscience
Anne Vejux, Amira Namsi, Thomas Nury, Thibault Moreau, Gérard Lizard
Amyotrophic lateral sclerosis (ALS) is a non-demyelinating neurodegenerative disease in adults with motor disorders. Two forms exist: a sporadic form (90% of cases) and a family form due to mutations in more than 20 genes including the Superoxide dismutase 1, TAR DNA Binding Protein, Fused in Sarcoma, chromosome 9 open reading frame 72 and VAPB genes. The mechanisms associated with this pathology are beginning to be known: oxidative stress, glutamate excitotoxicity, protein aggregation, reticulum endoplasmic stress, neuroinflammation, alteration of RNA metabolism...
2018: Frontiers in Molecular Neuroscience
Yang-Ja Lee, Joshua D Bernstock, Dace Klimanis, John M Hallenbeck
Hibernating 13-lined ground squirrels ( Ictidomys tridecemlineatus ; TLGS) rank among the most brain hypoperfusion-tolerant mammals known. Herein we provide some evidence of cycling between an epithelial phenotype and a hybrid epithelial/mesenchymal (E/M) phenotype (partial EMT) within the brains of TLGS during each bout of hibernation torpor. During hibernation torpor, expression of the epithelial marker E-cadherin (E-CDH) was reduced, while expression of the well-known mesenchymal markers vimentin and Sox2 were increased...
2018: Frontiers in Molecular Neuroscience
Marlen Dierich, Saskia Evers, Bettina U Wilke, Michael G Leitner
The three members of the ether-à-go-go-gene -like (Elk; Kv12.1-Kv12.3) family of voltage-gated K+channels are predominantly expressed in neurons, but only little information is available on their physiological relevance. It was shown that Kv12.2 channels modulate excitability of hippocampal neurons, but no native current could be attributed to Kv12.1 and Kv12.3 subunits yet. This may appear somewhat surprising, given high expression of their mRNA transcripts in several brain areas. Native Kv12 currents may have been overlooked so far due to limited knowledge on their biophysical properties and lack of specific pharmacology...
2018: Frontiers in Molecular Neuroscience
Mingxia Bi, Qian Jiao, Xixun Du, Hong Jiang
Considerable evidence has shown that elevated plasma or cerebrospinal fluid (CSF) urate levels correlated with a reduced risk of Parkinson's disease (PD). Based on its anti-oxidative properties, urate might serve as one of promising neuroprotective candidates for PD. However, how urate is transported through cell membranes to exert its effects inside the cells in PD is largely unknown. To elucidate this, we showed that increased intracellular urate exerted its neuroprotective effects against 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in MES23...
2018: Frontiers in Molecular Neuroscience
Charlotte Veyrat-Durebex, Pascal Reynier, Vincent Procaccio, Rudolf Hergesheimer, Philippe Corcia, Christian R Andres, Hélène Blasco
A ketogenic diet (KD) is a normocaloric diet composed by high fat (80-90%), low carbohydrate, and low protein consumption that induces fasting-like effects. KD increases ketone body (KBs) production and its concentration in the blood, providing the brain an alternative energy supply that enhances oxidative mitochondrial metabolism. In addition to its profound impact on neuro-metabolism and bioenergetics, the neuroprotective effect of specific polyunsaturated fatty acids and KBs involves pleiotropic mechanisms, such as the modulation of neuronal membrane excitability, inflammation, or reactive oxygen species production...
2018: Frontiers in Molecular Neuroscience
Giuseppe Condomitti, Joris de Wit
Neural circuits consist of distinct neuronal cell types connected in specific patterns. The specificity of these connections is achieved in a series of sequential developmental steps that involve the targeting of neurites, the identification of synaptic partners, and the formation of specific types of synapses. Cell-surface proteins play a critical role in each of these steps. The heparan sulfate proteoglycan (HSPG) family of cell-surface proteins is emerging as a key regulator of connectivity. HSPGs are expressed throughout brain development and play important roles in axon guidance, synapse development and synapse function...
2018: Frontiers in Molecular Neuroscience
Karina Karis, Kattri-Liis Eskla, Maria Kaare, Karin Täht, Jana Tuusov, Tanel Visnapuu, Jürgen Innos, Mohan Jayaram, Tõnis Timmusk, Cynthia S Weickert, Marika Väli, Eero Vasar, Mari-Anne Philips
Neural adhesion proteins are crucial in the development and maintenance of functional neural connectivity. Growing evidence suggests that the IgLON family of neural adhesion molecules LSAMP, NTM, NEGR1, and OPCML are important candidates in forming the susceptibility to schizophrenia (SCZ). IgLON proteins have been shown to be involved in neurite outgrowth, synaptic plasticity and neuronal connectivity, all of which have been shown to be altered in the brains of patients with the diagnosis of schizophrenia...
2018: Frontiers in Molecular Neuroscience
Ksenija Zega, Vukasin M Jovanovic, Zagorka Vitic, Magdalena Niedzielska, Laura Knaapi, Marin M Jukic, Juha Partanen, Roland H Friedel, Roland Lang, Claude Brodski
[This corrects the article on p. 372 in vol. 10, PMID: 29170629.].
2018: Frontiers in Molecular Neuroscience
Cai Shi, Jia Zeng, Zixi Li, Qingjie Chen, Weijian Hang, Liangtao Xia, Yue Wu, Juan Chen, Anbing Shi
Kainic acid (KA) exposure causes neuronal degeneration featured by Alzheimer-like tau hyperphosphorylation and memory deficits. Melatonin (Mel) is known to protect hippocampal neurons against KA-induced damage. However, the underlying mechanisms remain elusive. In the current study, we investigated the protective effect of melatonin on KA-induced tau hyperphosphorylation by focusing on endoplasmic reticulum (ER) stress-mediated signaling pathways. By using primary hippocampal neurons and mouse brain, we showed that KA treatment specifically induced ER stress and activated GSK-3β and CDK5, two major kinases responsible for tau phosphorylation...
2018: Frontiers in Molecular Neuroscience
Chih-Yen Wang, Yuan-Ting Sun, Kuan-Min Fang, Chia-Hsin Ho, Chung-Shi Yang, Shun-Fen Tzeng
B-cell CLL/lymphoma 11B (Bcl11b) - a C2H2 zinc finger transcriptional factor - is known to regulate neuronal differentiation and function in the development of the central nervous system (CNS). Although its expression is reduced during oligodendrocyte (OLG) differentiation, its biological role in OLGs remains unknown. In this study, we found that the downregulation of Bcl11b gene expression in glial progenitor cells (GPCs) by lentivirus-mediated gene knockdown (KD) causes a reduction in cell proliferation with inhibited expression of stemness-related genes, while increasing the expression of cell cyclin regulator p21...
2018: Frontiers in Molecular Neuroscience
Celine Brooks, Joseph Murphy, Marycharmain Belcastro, Daniel Heller, Saravanan Kolandaivelu, Oleg Kisselev, Maxim Sokolov
Primary cilia are microtubule-based organelles, which protrude from the plasma membrane and receive a wide range of extracellular signals. Various cilia use G protein-coupled receptors (GPCRs) for the detection of these signals. For instance, vertebrate rod photoreceptors use their cilia (also called outer segments) as antennae detecting photons by GPCR rhodopsin. Rhodopsin recognizes incoming light and activates its G protein, transducin, which is composed of three subunits α, β, and γ. Similar to all G protein γ subunits, the transducin Gγ1 subunit undergoes C-terminal prenylation resulting in the addition of an isoprenoid farnesyl; however, the significance of this posttranslational modification is unclear...
2018: Frontiers in Molecular Neuroscience
Timothy J Tracey, Frederik J Steyn, Ernst J Wolvetang, Shyuan T Ngo
Lipids are a fundamental class of organic molecules implicated in a wide range of biological processes related to their structural diversity, and based on this can be broadly classified into five categories; fatty acids, triacylglycerols (TAGs), phospholipids, sterol lipids and sphingolipids. Different lipid classes play major roles in neuronal cell populations; they can be used as energy substrates, act as building blocks for cellular structural machinery, serve as bioactive molecules, or a combination of each...
2018: Frontiers in Molecular Neuroscience
Corinna Martin, Carolin Stoffer, Milad Mohammadi, Julian Hugo, Enrico Leipold, Beatrice Oehler, Heike L Rittner, Robert Blum
Oxidized phospholipids (OxPL) like oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) were recently identified as novel proalgesic targets in acute and chronic inflammatory pain. These endogenous chemical irritants are generated in inflamed tissue and mediate their pain-inducing function by activating the transient receptor potential channels TRPA1 and TRPV1 expressed in sensory neurons. Notably, prototypical therapeutics interfering with OxPL were shown to inhibit TRP channel activation and pain behavior...
2018: Frontiers in Molecular Neuroscience
Xin-Yuan Cao, Xu Hua, Jian-Wei Xiong, Wen-Ting Zhu, Jun Zhang, Ling Chen
Triclosan (TCS), a broad-spectrum antimicrobial agent, is widely used in clinical settings and various personal care products. The aim of this study was to evaluate the influence of TCS on reproductive endocrine and function. Here, we show that the exposure of adult female mice to 10 or 100 mg/kg/day TCS caused prolongation of diestrus, and decreases in antral follicles and corpora lutea within 2 weeks. TCS mice showed decreases in the levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone, and gonadotrophin-releasing hormone (GnRH) mRNA with the lack of LH surge and elevation of prolactin (PRL)...
2018: Frontiers in Molecular Neuroscience
Pauline Vercruysse, Didier Vieau, David Blum, Åsa Petersén, Luc Dupuis
Neurodegenerative diseases (NDDs) are disorders characterized by progressive deterioration of brain structure and function. Selective neuronal populations are affected leading to symptoms which are prominently motor in amyotrophic lateral sclerosis (ALS) or Huntington's disease (HD), or cognitive in Alzheimer's disease (AD) and fronto-temporal dementia (FTD). Besides the common existence of neuronal loss, NDDs are also associated with metabolic changes such as weight gain, weight loss, loss of fat mass, as well as with altered feeding behavior...
2018: Frontiers in Molecular Neuroscience
Hannah I Bishop, Melanie M Cobb, Michael Kirmiz, Laxmi K Parajuli, Danielle Mandikian, Ashleigh M Philp, Mikhail Melnik, Juha Kuja-Panula, Heikki Rauvala, Ryuichi Shigemoto, Karl D Murray, James S Trimmer
Voltage-gated K+ (Kv) channels play important roles in regulating neuronal excitability. Kv channels comprise four principal α subunits, and transmembrane and/or cytoplasmic auxiliary subunits that modify diverse aspects of channel function. AMIGO-1, which mediates homophilic cell adhesion underlying neurite outgrowth and fasciculation during development, has recently been shown to be an auxiliary subunit of adult brain Kv2.1-containing Kv channels. We show that AMIGO-1 is extensively colocalized with both Kv2...
2018: Frontiers in Molecular Neuroscience
Asier Ruiz, Elena Alberdi, Carlos Matute
Excessive dynamin related protein 1 (Drp1)-triggered mitochondrial fission contributes to apoptosis under pathological conditions and therefore it has emerged as a promising therapeutic target. Mitochondrial division inhibitor 1 (mdivi-1) inhibits Drp1-dependent mitochondrial fission and is neuroprotective in several models of brain ischemia and neurodegeneration. However, mdivi-1 also modulates mitochondrial function and oxidative stress independently of Drp1, and consequently the mechanisms through which it protects against neuronal injury are more complex than previously foreseen...
2018: Frontiers in Molecular Neuroscience
Oswald Steward, Kelly Matsudaira Yee, Shannon Farris, Patricia S Pirbhoy, Paul Worley, Kohji Okamura, Hiroyuki Okuno, Haruhiko Bito
Arc is a unique immediate early gene (IEG) whose expression is induced as synapses are modified during learning. Newly-synthesized Arc mRNA is rapidly transported throughout dendrites and localizes near recently activated synapses. Arc mRNA levels are regulated by rapid degradation, which is accelerated by synaptic activity in a translation-dependent process. One possible mechanism is nonsense-mediated mRNA decay (NMD), which depends on the presence of a splice junction in the 3'UTR. Here, we test this hypothesis using transgenic mice that express EGFP-Arc ...
2017: Frontiers in Molecular Neuroscience
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