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Molecular and Cellular Neurosciences

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https://www.readbyqxmd.com/read/28720530/downregulation-of-protein-phosphatase-2a-by-apolipoprotein-e-implications-for-alzheimer-s-disease
#1
Veena Theendakara, Dale E Bredesen, Rammohan V Rao
The apolipoprotein E ε4 allele is the single most important genetic risk factor associated with Alzheimer's disease (AD). Tau phosphorylation and hyperphosphorylation is an underlying feature of AD and is regulated by specific kinases and phosphatases. Among phosphatases, protein phosphatase 2A (PP2A) is the principal tau dephosphorylating enzyme in the brain. Several abnormalities of PP2A have been reported in AD, including among others decreased protein levels of PP2A, decreased mRNA and protein levels of the catalytic subunit PP2AC and variable regulatory B subunits and reduced methylation of the catalytic subunit, all of which results in disruption of the PP2A phosphatase activity...
July 15, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28690173/immediate-and-delayed-hyperbaric-oxygen-therapy-as-a-neuroprotective-treatment-for-traumatic-brain-injury-in-mice
#2
Renana Baratz-Goldstein, Shlomi Toussia-Cohen, Aviya Elpaz, Vardit Rubovitch, Chaim G Pick
BACKGROUND: Traumatic brain injury is the most common cause of death or chronic disability among people under-35-years-old. There is no effective pharmacological treatment currently existing for TBI. Hyperbaric oxygen therapy (HBOT) is defined as the inhalation of pure oxygen in a hyperbaric chamber that is pressurized higher than 1atm. HBOT offers physiological and mechanical effects by inducing a state of increased pressure and hyperoxia. HBOT has been proposed as an effective treatment for moderate traumatic brain injury (mTBI), yet the exact therapeutic window and mechanism that underlies this effect is not completely understood...
July 8, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28687523/tdp-43-in-the-spectrum-of-mnd-ftld-pathologies
#3
REVIEW
Lanier Heyburn, Charbel E-H Moussa
The relationship between RNA-binding proteins, particularly TAR DNA binding protein 43 (TDP-43), and neurodegeneration is an important area of research. TDP-43 is involved in so many cellular processes that perturbation of protein homeostasis can lead to countless downstream effects. Understanding what leads to this disease-related protein imbalance and the resulting cellular and molecular effects will help to develop targets for disease intervention, whether it be prevention of protein accumulation, or addressing a secondary effect of protein accumulation...
July 4, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28684360/regulator-of-g-protein-signaling-5-rgs5-inhibits-sonic-hedgehog-function-in-mouse-cortical-neurons
#4
Chuanliang Liu, Qiongqiong Hu, Jia Jing, Yun Zhang, Jing Jin, Liulei Zhang, Lili Mu, Yumei Liu, Bo Sun, Tongshuai Zhang, Qingfei Kong, Guangyou Wang, Dandan Wang, Yao Zhang, Xijun Liu, Wei Zhao, Jinghua Wang, Tao Feng, Hulun Li
Regulator of G protein signaling 5 (RGS5) acts as a GTPase-activating protein (GAP) for the Gαi subunit and negatively regulates G protein-coupled receptor signaling. However, its presence and function in postmitotic differentiated primary neurons remains largely uncharacterized. During neural development, sonic hedgehog (Shh) signaling is involved in cell signaling pathways via Gαi activity. In particular, Shh signaling is essential for embryonic neural tube patterning, which has been implicated in neuronal polarization involving neurite outgrowth...
July 3, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28676376/cutaneous-inflammation-regulates-thik1-expression-in-small-c-like-nociceptor-dorsal-root-ganglion-neurons
#5
William Haskins, Sergio Benitez, Juan M Mercado, Cristian G Acosta
Tandem pore-domain Halothane Inhibited K(+) channel (THIK1) is a two-pore-domain potassium channel (K2P) present in dorsal root ganglia (DRG). We previously demonstrated that THIK1 mRNA levels in the DRG dropped ipsilaterally 1day after CFA-induced cutaneous inflammation (CFA1). In this study we aimed to identify the currently unknown DRG subpopulations expressing THIK1, and to investigate the relationship between the channel and both inflammatory and spontaneous pain in normal rats. Using a combination of immunohistochemistry, western blotting and behavioural tests, we found that all small neurons and large groups of medium and large DRG neurons express THIK1...
July 1, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28673772/methyl-4-phenylpyridinium-mpp-differentially-affects-monoamine-release-and-re-uptake-in-murine-embryonic-stem-cell-derived-dopaminergic-and-serotonergic-neurons
#6
Yasmina Martí, Friederike Matthaeus, Thorsten Lau, Patrick Schloss
1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) is known to selectively damage dopaminergic (DA) cells in the substantia nigra and to produce symptoms which are alike to those observed in Parkinson's disease (PD). Based on the similarity between MPTP-induced neurotoxicity and PD-related neuropathology, application of MPTP or its metabolite methyl-4-phenylpyridinium (MPP+) was successfully established in experimental rodent models to study PD-related neurodegenerative events. MPP+ is taken up by the dopamine transporter (DAT) into DA neurons where it exerts its neurotoxic action on mitochondria by affecting complex I of the respiratory chain...
June 30, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28669622/smad4-is-essential-for-directional-progression-from-committed-neural-progenitor-cells-through-neuronal-differentiation-in-the-postnatal-mouse-brain
#7
Motoko Kawaguchi-Niida, Noriyuki Shibata, Yasuhide Furuta
Signaling by the TGFβ super-family, consisting of TGFβ/activin- and bone morphogenetic protein (BMP) branch pathways, is involved in the central nervous system patterning, growth, and differentiation during embryogenesis. Neural progenitor cells are implicated in various pathological conditions, such as brain injury, infarction, Parkinson's disease and Alzheimer's disease. However, the roles of TGFβ/BMP signaling in the postnatal neural progenitor cells in the brain are still poorly understood. We examined the functional contribution of Smad4, a key integrator of TGFβ/BMP signaling pathways, to the regulation of neural progenitor cells in the subventricular zone (SVZ)...
June 29, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28666963/a-novel-kcna1-mutation-in-a-patient-with-paroxysmal-ataxia-myokymia-painful-contractures-and-metabolic-dysfunctions
#8
Paola Imbrici, Concetta Altamura, Francesca Gualandi, Giuseppe Felice Mangiatordi, Marcella Neri, Giovanni De Maria, Alessandra Ferlini, Alessandro Padovani, Maria Cristina D'Adamo, Orazio Nicolotti, Mauro Pessia, Diana Conte, Massimiliano Filosto, Jean-Francois Desaphy
Episodic ataxia type 1 (EA1) is a human dominant neurological syndrome characterized by continuous myokymia, episodic attacks of ataxic gait and spastic contractions of skeletal muscles that can be triggered by emotional stress and fatigue. This rare disease is caused by missense mutations in the KCNA1 gene coding for the neuronal voltage gated potassium channel Kv1.1, which contributes to nerve cell excitability in the cerebellum, hippocampus, cortex and peripheral nervous system. We identified a novel KCNA1 mutation, E283K, in an Italian proband presenting with paroxysmal ataxia and myokymia aggravated by painful contractures and metabolic dysfunctions...
June 28, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28666962/decreased-calcium-flux-in-niemann-pick-type-c1-patient-specific-ipsc-derived-neurons-due-to-higher-amount-of-calcium-impermeable-ampa-receptors
#9
Michael Rabenstein, Franziska Peter, Sarah Joost, Michaela Trilck, Arndt Rolfs, Moritz J Frech
Niemann-Pick disease type C1 (NPC1) is a rare progressive neurodegenerative disorder caused by mutations in the NPC1 gene, resulting mainly in the accumulation of cholesterol and the ganglioside GM2. Recently, we described accumulations of these lipids in neuronal differentiated cells derived from NPC1 patient-specific induced pluripotent stem cells (iPSCs). As these lipids are essential for proper cell membrane composition, we were interested in the expression and function of voltage-gated ion channels and excitatory AMPA receptors (AMPARs) in neurons derived from three patient-specific iPSC lines...
June 27, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28642089/involvement-of-mapk-akt-gsk-3%C3%AE-and-ampk-mtor-signaling-pathways-in-protection-of-remote-glial-cells-from-axotomy-induced-necrosis-and-apoptosis-in-the-isolated-crayfish-stretch-receptor
#10
E V Berezhnaya, M Y Bibov, M A Komandirov, M A Neginskaya, M V Rudkovskii, A B Uzdensky
Severe mechanical nerve injury such as axotomy can lead to neuron degeneration and death of surrounding glial cells. We showed that axotomy not only mechanically injures glial cells at the cutting location, but also induces necrosis or apoptosis of satellite glial cells remote from the transection site. Therefore, axon integrity is necessary for survival of surrounding glial cells. We used the crayfish stretch receptor that consists of a single mechanoreceptor neuron enveloped by satellite glial cells as a simple, but informative model object in the study of the role of various signaling proteins in axotomy-induced death of remote glial cells...
June 20, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28600222/taste-bud-derived-bdnf-maintains-innervation-of-a-subset-of-trkb-expressing-gustatory-nerve-fibers
#11
Tao Tang, Jennifer Rios-Pilier, Robin Krimm
Taste receptor cells transduce different types of taste stimuli and transmit this information to gustatory neurons that carry it to the brain. Taste receptor cells turn over continuously in adulthood, requiring constant new innervation from nerve fibers. Therefore, the maintenance of innervation to taste buds is an active process mediated by many factors, including brain-derived neurotrophic factor (BDNF). Specifically, 40% of taste bud innervation is lost when Bdnf is removed during adulthood. Here we speculated that not all gustatory nerve fibers express the BDNF receptor, TrkB, resulting in subsets of neurons that vary in their response to BDNF...
June 20, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28625609/oxidative-stress-induced-by-cumene-hydroperoxide-produces-synaptic-depression-and-transient-hyperexcitability-in-rat-primary-motor-cortex-neurons
#12
R Pardillo-Diaz, L Carrascal, G Barrionuevo, P Nunez-Abades
Pyramidal neurons of the motor cortex are selectively degenerated in Amyotrophic Lateral Sclerosis (ALS). The mechanisms underlying neuronal death in ALS are not well established. In the absence of useful biomarkers, the early increased neuronal excitability seems to be the unique characteristic of ALS. Lipid peroxidation caused by oxidative stress has been postulated as one of the possible mechanisms involved in degeneration motor cortex pyramidal neurons. This paper examines the effect of lipid peroxidation on layer V pyramidal neurons induced by cumene hydroperoxide (CH) in brain slices from wild type rats...
June 15, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28554564/the-third-wave-intermediate-filaments-in-the-maturing-nervous-system
#13
REVIEW
Matthew T K Kirkcaldie, Samuel T Dwyer
Intermediate filaments are critical for the extreme structural specialisations of neurons, providing integrity in dynamic environments and efficient communication along axons a metre or more in length. As neurons mature, an initial expression of nestin and vimentin gives way to α-internexin and the neurofilament triplet proteins, substituted by peripherin in axons outside the CNS, physically consolidating axons as they elongate and find their targets. Once connection is established, these proteins are transported, assembled, stabilised and modified, structurally transforming axons and dendrites as they acquire their full function...
May 26, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28552341/methamphetamine-potentiates-hiv-1gp120-induced-microglial-neurotoxic-activity-by-enhancing-microglial-outward-k-current
#14
Jianuo Liu, Enquan Xu, Guihua Tu, Han Liu, Jiangtao Luo, Huangui Xiong
Methamphetamine (Meth) abuse not only increases the risk of human immunodeficiency virus-1 (HIV-1) infection, but exacerbates HIV-1-associated neurocognitive disorders (HAND) as well. The mechanisms underlying the co-morbid effect are not fully understood. Meth and HIV-1 each alone interacts with microglia and microglia express voltage-gated potassium (KV) channel KV1.3. To understand whether KV1.3 functions an intersecting point for Meth and HIV-1, we studied the augment effect of Meth on HIV-1 glycoprotein 120 (gp120)-induced neurotoxic activity in cultured rat microglial cells...
May 25, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28552342/interplay-between-mitochondrial-metabolism-and-oxidative-stress-in-ischemic-stroke-an-epigenetic-connection
#15
REVIEW
Parimala Narne, Vimal Pandey, Prakash Babu Phanithi
The advent of epigenetics brought in a tectonic shift in the understanding of molecular basis of complex diseases like ischemic stroke (IS). Substantial scientific inquiry into the epigenetic basis of neurodegenerative diseases has bolstered the idea that altered carbon flux into central carbon metabolism and disturbed redox states govern the attendant transcriptional profiles through stochastic epigenetic changes. In view of an increasing understanding of the link between mitochondrial energy metabolism, oxidative stress and epigenetics in IS, the hitherto underappreciated 'neuroenergetics' is gaining sustained attention...
May 24, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28545680/a-role-for-tropomyosins-in-activity-dependent-bulk-endocytosis
#16
REVIEW
R S Gormal, N Valmas, T Fath, F A Meunier
Bulk endocytosis allows stimulated neurons to take up a large portion of the presynaptic plasma membrane in order to regenerate synaptic vesicle pools. Actin, one of the most abundant proteins in eukaryotic cells, plays an important role in this process, but a detailed mechanistic understanding of the involvement of the cortical actin network is still lacking, in part due to the relatively small size of nerve terminals and the limitation of optical microscopy. We recently discovered that neurosecretory cells display a similar, albeit much larger, form of bulk endocytosis in response to secretagogue stimulation...
May 22, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28536001/membrane-shaping-by-actin-and-myosin-during-regulated-exocytosis
#17
REVIEW
Andreas Papadopulos
The cortical actin network in neurosecretory cells is a dense mesh of actin filaments underlying the plasma membrane. Interaction of actomyosin with vesicular membranes or the plasma membrane is vital for tethering, retention, transport as well as fusion and fission of exo- and endocytic membrane structures. During regulated exocytosis the cortical actin network undergoes dramatic changes in morphology to accommodate vesicle docking, fusion and replenishment. Most of these processes involve plasma membrane Phosphoinositides (PIP) and investigating the interactions between the actin cortex and secretory structures has become a hotbed for research in recent years...
May 20, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28506637/thiamine-and-benfotiamine-prevent-stress-induced-suppression-of-hippocampal-neurogenesis-in-mice-exposed-to-predation-without-affecting-brain-thiamine-diphosphate-levels
#18
Julie Vignisse, Margaux Sambon, Anna Gorlova, Dmitrii Pavlov, Nicolas Caron, Brigitte Malgrange, Elena Shevtsova, Andrey Svistunov, Daniel C Anthony, Natalyia Markova, Natalyia Bazhenova, Bernard Coumans, Bernard Lakaye, Pierre Wins, Tatyana Strekalova, Lucien Bettendorff
Thiamine is essential for normal brain function and its deficiency causes metabolic impairment, specific lesions, oxidative damage and reduced adult hippocampal neurogenesis (AHN). Thiamine precursors with increased bioavailability, especially benfotiamine, exert neuroprotective effects not only for thiamine deficiency (TD), but also in mouse models of neurodegeneration. As it is known that AHN is impaired by stress in rodents, we exposed C57BL6/J mice to predator stress for 5 consecutive nights and studied the proliferation (number of Ki67-positive cells) and survival (number of BrdU-positive cells) of newborn immature neurons in the subgranular zone of the dentate gyrus...
May 12, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28495450/rho-guanine-nucleotide-exchange-factor-rgnef-is-a-prosurvival-factor-under-stress-conditions
#19
Kevin Cheung, Cristian A Droppelmann, Adam MacLellan, Ian Cameron, Benjamin Withers, Danae Campos-Melo, Kathryn Volkening, Michael J Strong
Rho guanine nucleotide exchange factor (RGNEF) is a 190kDa RNA binding protein (RBP) that also contains a Dbl/PH domain capable of RhoA activation. Consistent with a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS), RGNEF forms pathological neuronal cytoplasmic inclusions in degenerating spinal motor neurons. To further understand the role of RGNEF in the stress response, we first observed that the expression of RGNEF is upregulated in murine spinal motor neurons following distal sciatic nerve injury...
May 8, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28479292/new-waves-in-dendritic-spine-actin-cytoskeleton-from-branches-and-bundles-to-rings-from-actin-binding-proteins-to-post-translational-modifications
#20
REVIEW
Enni Bertling, Pirta Hotulainen
Dendritic spines are small actin-rich protrusions from neuronal dendrites that form the postsynaptic part of most excitatory synapses. Changes in the number or strength of synapses are physiological mechanisms behind learning. The growth and maturation of dendritic spines and the activity-induced changes to their morphology are all based on changes to the actin cytoskeleton. In this review, we will discuss the regulation of the actin cytoskeleton in dendritic spine formation and maturation, as well as in synaptic strengthening...
May 4, 2017: Molecular and Cellular Neurosciences
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