Journal of Neurochemistry

Cover image for Vol. 139 Issue 1

Early View (Online Version of Record published before inclusion in an issue)

Edited By: Jörg Schulz

Impact Factor: 3.842

ISI Journal Citation Reports © Ranking: 2015: 71/256 (Neurosciences); 83/289 (Biochemistry & Molecular Biology)

Online ISSN: 1471-4159

  1. Reviews

    1. You have free access to this content
      Role of GABAAR trafficking in the plasticity of inhibitory synapses

      Miranda Mele, Graciano Leal and Carlos B. Duarte

      Version of Record online: 30 SEP 2016 | DOI: 10.1111/jnc.13742

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      In this work, we review some of the mechanisms contributing to the plasticity of inhibitory synapses in the CNS, focusing on the regulation of GABAA receptor (GABAAR) trafficking in response to alterations in neuronal activity or to stimulation of different classes of plasma membrane-associated receptors. Alterations in these mechanisms are important in the refinement of neuronal network activity.

  2. Original Articles

    1. Isoforms of the Erythropoietin receptor in dopaminergic neurons of the Substantia Nigra

      Federica Marcuzzi, Silvia Zucchelli, Maria Bertuzzi, Claudio Santoro, Gianluca Tell, Piero Carninci and Stefano Gustincich

      Version of Record online: 30 SEP 2016 | DOI: 10.1111/jnc.13757

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      Selective degeneration of A9 dopaminergic neurons leads to Parkinson's disease. We apply genome-wide promoter identification technologies to identify A9-specific transcripts. In isolated A9 neurons, we identify new variants of erythropoietin receptor (DA-EpoR). DA-EpoR transcript encodes for a N-terminal truncated receptor. Based on STAT5 phosphorylation assays, we show that the new variant of N-terminally truncated EpoR acts as decoy when co-expressed with the full-length form. A similar isoform is also found in human.

    2. Homocysteine metabolism is associated with cerebrospinal fluid levels of soluble amyloid precursor protein and amyloid beta

      Aikaterini Oikonomidi, Piotr Lewczuk, Johannes Kornhuber, Yvo Smulders, Michael Linnebank, Alexander Semmler and Julius Popp

      Version of Record online: 30 SEP 2016 | DOI: 10.1111/jnc.13766

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      Disturbed homocysteine metabolism may contribute to amyloidogenesis by modulating the amyloid precursor protein (APP) production and processing. We found associations between CSF levels of soluble APP forms and Aβ1-42, and markers of the homocysteine metabolism in both plasma and CSF in adults with normal cognition. Disturbed homocysteine metabolism may represent a target for preventive and early disease-modifying interventions in Alzheimer's disease.

    3. Reference measurement procedure for CSF amyloid beta (Aβ)1–42 and the CSF Aβ1–42/Aβ1–40 ratio – a cross-validation study against amyloid PET

      Josef Pannee, Erik Portelius, Lennart Minthon, Johan Gobom, Ulf Andreasson, Henrik Zetterberg, Oskar Hansson and Kaj Blennow

      Version of Record online: 30 SEP 2016 | DOI: 10.1111/jnc.13838

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      The aim of this study was to cross-validate the Reference Measurement Procedure for amyloid β 1–42 (Aβ1–42) as well as the Aβ1–42/Aβ1–40 and Aβ1–42/Aβ1–38 ratios in cerebrospinal fluid (CSF), measured by mass spectrometry (MS), with the cortical level of Aβ fibrils as measured by positron emission tomography (PET). Our findings show that the CSF Aβ1–42/Aβ1–40 and Aβ1–42/Aβ1–38 ratios using the described MS method are strongly associated with the level of cortical Aβ fibrils, and that the ratios of Aβ1–42/Aβ1–40 (or Aβ1–42/Aβ1–38) is superior to using Aβ1–42 alone.

    4. Calpain inhibition reduces structural and functional impairment of retinal ganglion cells in experimental optic neuritis

      Amena W. Smith, Baerbel Rohrer, Lee Wheless, Supriti Samantaray, Swapan K. Ray, Jun Inoue, Mitsuyoshi Azuma and Naren L. Banik

      Version of Record online: 27 SEP 2016 | DOI: 10.1111/jnc.13770

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      As in multiple sclerosis (MS) patients, optic neuritis (ON) and early, primarily monocular loss in spatial acuity is observed in a rodent model (EAE, experimental autoimmune encephalomyelitis). Daily oral treatment with the calpain inhibitor SNJ 1945 preserves visual acuity and preserves retinal ganglion cells (Brn3a, brain-specific homeobox/POU domain protein 3A) and their axons (MOSP, myelin oligodendrocyte-specific protein). Calpain inhibition may represent a candidate therapy for the preservation of vision in ON.

    5. Tyrosine kinase inhibition reverses TDP-43 effects on synaptic protein expression, astrocytic function and amino acid dis-homeostasis

      Lanier Heyburn, Michaeline L. Hebron, Jacqueline Smith, Charisse Winston, John Bechara, Zhaoxia Li, Irina Lonskaya, Mark P. Burns, Brent T. Harris and Charbel E.-H. Moussa

      Version of Record online: 27 SEP 2016 | DOI: 10.1111/jnc.13763

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      To analyze molecular mechanism underlying the trans-activating response of DNA/RNA-binding protein (TDP)-43 pathology, transgenic mice over-expressing human TDP-43 were analyzed for their glutamate metabolism and synaptic function. Over-expression of TDP-43 leads to reduction of presynaptic protein expression, including synaptotagmin and synapsin and decreased astrocytic activity. Furthermore, it increases levels of glutamate and GABA and reduces levels of glutamine and aspartate, suggesting impairment of the neuronal-astrocytic glutamate–glutamine cycle. TDP-43 also decreases tricarboxylic acid metabolism and induces oxidative stress via lactate accumulation. Treatment of TDP-43 transgenic mice with tyrosine kinase inhibitors (TKIs) leads to an increase in astrocyte function, restoration of neurotransmitter homeostasis, reduction of oxidative stress and a decrease in VEGF levels. It is hypothesized that TKIs reduce TDP-43 levels in neurons and increase presynaptic protein levels, leading to restoration of glutamate detoxification via the glutamate–glutamine cycle in activated astrocytes.

    6. Imaging mass spectrometry reveals loss of polyunsaturated cardiolipins in the cortical contusion, hippocampus, and thalamus after traumatic brain injury

      Louis J. Sparvero, Andrew A. Amoscato, Arthur B. Fink, Tamil Anthonymuthu, Lee Ann New, Patrick M. Kochanek, Simon Watkins, Valerian E. Kagan and Hulya Bayır

      Version of Record online: 26 SEP 2016 | DOI: 10.1111/jnc.13840

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      Traumatic brain injury (TBI) leads to changes in ion fluxes and alterations in mitochondrial function. Mitochondrial signaling strongly depends on cardiolipin (CL), which is selectively oxidized and presents itself as a target for redox therapy following TBI. We describe a mass spectrometric lipid imaging study that reports regio-specific changes in rat brain CL in a controlled cortical impact (CCI) model of traumatic brain injury (TBI). While MALDI-MS imaging revealed that TBI caused decreases in CL in the contusional area 3 h after injury, it also revealed decreases extending well beyond the area of impact into histologically normal tissue in the hippocampus and thalamic regions. The more unsaturated CL species were most susceptible to loss.

    7. Cannabinoid receptor interacting protein suppresses agonist-driven CB1 receptor internalization and regulates receptor replenishment in an agonist-biased manner

      Lawrence C. Blume, Sandra Leone-Kabler, Deborah J. Luessen, Glen S. Marrs, Erica Lyons, Caroline E. Bass, Rong Chen, Dana E. Selley and Allyn C. Howlett

      Version of Record online: 26 SEP 2016 | DOI: 10.1111/jnc.13767

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      The CB1R-interacting protein CRIP1a functions to differentially modulate agonist-promoted versus non-agonist-mediated CB1R internalization and cell surface equilibrium. Association of CRIP1a with the CB1R precludes agonist-driven internalization via a mechanism involving β-arrestin, clathrin and dynamin. CRIP1a also functions to fine-tune CB1R cell surface levels through delivery of newly synthesized CB1R receptors to the plasma membrane.

  3. Obituary

    1. Victor P. Whittaker (1919–2016)

      Herbert Zimmermann and Frode Fonnum

      Version of Record online: 23 SEP 2016 | DOI: 10.1111/jnc.13778

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      This Obituary honors Victor P. Whittaker, one of the pioneers in the field of neurochemistry. Victor Whittaker died on 5th July 2016 aged 97 in Cambridge (UK) after a short illness. Victor is best known for his landmark advances in the subcellular fractionation of brain tissue which led to the isolation of synaptosomes and subsequently synaptic vesicles at the beginning of the 1960s and for the cellular and molecular analysis of the cholinergic synapse.

  4. Original Articles

    1. MicroRNAs 29b and 181a down-regulate the expression of the norepinephrine transporter and glucocorticoid receptors in PC12 cells

      Maoxian Deng, Turan Tufan, Muhammad U. Raza, Thomas C. Jones and Meng-Yang Zhu

      Version of Record online: 22 SEP 2016 | DOI: 10.1111/jnc.13761

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      This study demonstrated that miR-29b and miR-181a, two short non-coding RNAs that provide global regulation of gene expression, markedly repressed protein levels of norepinephrine (NE) transporter and glucocorticoid receptor (GR), as well as NE uptake by binding the 3′UTR of their mRNAs in PC12 cells. Also, exposure of cells to corticosterone significantly reduced miR-29b levels through a GR-independent way.

    2. Role of Class III phosphoinositide 3-kinase in the brain development: possible involvement in specific learning disorders

      Yutaka Inaguma, Ayumi Matsumoto, Mariko Noda, Hidenori Tabata, Akihiko Maeda, Masahide Goto, Daisuke Usui, Eriko F. Jimbo, Kiyoshi Kikkawa, Mamitaro Ohtsuki, Mariko Y. Momoi, Hitoshi Osaka, Takanori Yamagata and Koh-ichi Nagata

      Version of Record online: 19 SEP 2016 | DOI: 10.1111/jnc.13832

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      Acute knockdown of Class III phosphoinositide 3-kinase (PIK3C3) evokes migration defects of excitatory neurons during corticogenesis. PIK3C3-knockdown also disrupts axon outgrowth, but not progenitor proliferation in vivo. Involvement of PIK3C3 in neurodevelopmental disorders might be an interesting future subject since a deletion mutation in PIK3C3 was detected in a patient with specific learning disorders (SLD).

    3. β-Caryophyllene protects in vitro neurovascular unit against oxygen-glucose deprivation and re-oxygenation-induced injury

      Xiaocui Tian, Jianhua Peng, Jianjun Zhong, Mei Yang, Jinwei Pang, Jie Lou, Minghang Li, Ruidi An, Qian Zhang, Lu Xu and Zhi Dong

      Version of Record online: 19 SEP 2016 | DOI: 10.1111/jnc.13833

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      β-Caryophyllene (BCP) pre-treatment exerts multiple protective effects on the neurovascular unit (NVU) in the context of oxygen-glucose deprivation and re-oxygenation (OGD/R)-induced injury. These effects potentially result from the inhibition of blood–brain barrier breakdown as well as neuronal apoptosis via decreased oxidative stress damage and inflammation. The NVU thus is a putative therapeutic target for cerebral ischemia, and BCP is a promising therapeutic candidate to treat CNS disorders involving NVU damage.

    4. Nrf2-dysregulation correlates with reduced synthesis and low glutathione levels in experimental autoimmune encephalomyelitis

      Itzy E. Morales Pantoja, Che-lin Hu, Nora I. Perrone-Bizzozero, Jianzheng Zheng and Oscar A. Bizzozero

      Version of Record online: 19 SEP 2016 | DOI: 10.1111/jnc.13837

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      We show that the concentration of glutathione [GSH] is reduced in the spinal cord of mice with experimental autoimmune encephalomyelitis. Low [GSH] is likely because of diminished expression of various GSH-synthesizing enzymes. These changes coincide with a decrease of Nrf2 (nuclear factor erythroid 2–related factor 2) protein levels, which does not seem to result from increased degradation. These findings are important for our understanding of how critical antioxidant and protective responses are lost during inflammatory demyelination.

    5. Chronic consumption of Annona muricata juice triggers and aggravates cerebral tau phosphorylation in wild-type and MAPT transgenic mice

      Robert Rottscholl, Marlen Haegele, Britta Jainsch, Hong Xu, Gesine Respondek, Matthias Höllerhage, Thomas W. Rösler, Emilie Bony, Jessica Le Ven, Vincent Guérineau, Isabelle Schmitz-Afonso, Pierre Champy, Wolfgang H. Oertel, Elizabeth S. Yamada and Günter U. Höglinger

      Version of Record online: 16 SEP 2016 | DOI: 10.1111/jnc.13835

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      Annona muricata juice is an environmental risk factor for Parkinsonism and dementia in Guadeloupe. We show that it contains neurotoxic Annonaceous acetogenins and isoquinoline alkaloids. Its chronic ingestion increases neuronal phospho-tau (AT8, AT100, AT180, AD2) and 3-nitrotyrosine (3NT), and decreases synaptophysin density in brains of non-transgenic (nTg) mice, and even more in mice over-expressing human wild-type or R406W mutant tau.

    6. Protein phosphatase PP2A – a novel interacting partner of carnitine transporter OCTN2 (SLC22A5) in rat astrocytes

      Barbara Juraszek and Katarzyna A. Nałęcz

      Version of Record online: 16 SEP 2016 | DOI: 10.1111/jnc.13777

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      Organic cation/carnitine transporter OCTN2 (SLC22A5) interacts with protein phosphatase 2 (PP2A) catalytical (C), structural (A), and regulatory subunits (striatins). One of striatins (SG2NA) dissociates from the complex, when phosphorylated by protein kinase C (PKC), leading to augmented transporter activity and presence in the plasma membrane, demonstrating a new mechanism regulating OCTN2 trafficking to the cell surface.

    7. Neuroprotective effects of antibodies on retinal ganglion cells in an adolescent retina organ culture

      Katharina Bell, Corina Wilding, Sebastian Funke, Natarajan Perumal, Sabine Beck, Dominik Wolters, Jana Holz-Müller, Norbert Pfeiffer and Franz H. Grus

      Version of Record online: 16 SEP 2016 | DOI: 10.1111/jnc.13765

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      Loss of retinal ganglion cells (rgc) in glaucoma leads to blindness. Several antibodies are down-regulated in glaucoma patients. Our aim was to test if these antibodies have a protective effect of rgc in a retinal organ culture. This could be shown with an increase of rgc numbers. This effect results through reduced stress levels and the shift of glutamine synthetase localization.

    8. C-terminal of human histamine H1 receptors regulates their agonist-induced clathrin-mediated internalization and G-protein signaling

      Shigeru Hishinuma, Hiroki Nozawa, Chizuru Akatsu and Masaru Shoji

      Version of Record online: 15 SEP 2016 | DOI: 10.1111/jnc.13834

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      The short C-terminal tail (Cys471-Ser487; 17 amino acids) of human histamine H1 receptors tagged with hemagglutinin (HA) at the N-terminal was revealed to play crucial roles in regulation of both histamine-induced internalization of H1 receptors and G-protein signaling, in which truncation of Ser487 and mutation of either Thr478 or Ser487 to alanine resulted in biased signaling toward activation of G-proteins and clathrin-mediated internalization, respectively.

    9. Tissue kallikrein protects SH-SY5Y neuronal cells against oxygen and glucose deprivation-induced injury through bradykinin B2 receptor-dependent regulation of autophagy induction

      Yanping Liu, Zhengyu Lu, Mei Cui, Qi Yang, Yuping Tang and Qiang Dong

      Version of Record online: 15 SEP 2016 | DOI: 10.1111/jnc.13690

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      We propose the depicted model for the neuroprotective mechanism of tissue kallikrein (TK) during OGD stress: TK enhances bradykinin B2 receptor (B2R)-mediated MEK1/2/ERK1/2 and AMPK/TSC2/mTOR signaling, thus inducing protective autophagy. The findings reported in this study should provide new evidence for the pro-survival role of B2R-mediated autophagy in cerebral ischemia.

    10. HDAC1 negatively regulates Bdnf and Pvalb required for parvalbumin interneuron maturation in an experience-dependent manner

      Dawn X. P. Koh and Judy C. G. Sng

      Version of Record online: 15 SEP 2016 | DOI: 10.1111/jnc.13773

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      We proposed that whisker deprivation causes changes in the epigenome altering excitatory/inhibitory balance in the primary somatosensory cortex S1. We demonstrated increased histone deacetylase HDAC1 activity and expression with whisker deprivation, accompanied by increased HDAC1 and HDAC2 association at Bdnf (brain-derived neurotrophic factor) and Pvalb (parvalbumin) resulting in decreased histone acetylation and gene transcription. Our findings provide new insight on experience-dependent epigenetic mechanisms during brain development.

  5. Reviews

    1. You have free access to this content
      Pathogenic mechanisms of prion protein, amyloid-β and α-synuclein misfolding: the prion concept and neurotoxicity of protein oligomers

      Cathryn L. Ugalde, David I. Finkelstein, Victoria A. Lawson and Andrew F. Hill

      Version of Record online: 15 SEP 2016 | DOI: 10.1111/jnc.13772

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      Several proteins are known to misfold and accumulate in the central nervous system causing a range of neurodegenerative diseases, such as Alzheimer's, Parkinson's, and the prion diseases. Prions are transmissible misfolded conformers of the prion protein, PrP, which seed further generation of infectious proteins. Similar effects have recently been observed in proteins associated with Alzheimer's disease and the synucleinopathies, leading to the proposition that the definition of a ‘prion’ may ultimately expand to include other pathogenic proteins. Unifying knowledge of misfolded proteins may also reveal common mechanisms associated with other features of disease that are less understood, such as neurotoxicity.