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Journal of Neurochemistry

Cover image for Vol. 121 Issue 6

June 2012

Volume 121, Issue 6

Pages 841–1016

  1. EDITORIAL HIGHLIGHT

    1. Top of page
    2. EDITORIAL HIGHLIGHT
    3. SHORT COMMUNICATIONS
    4. ORIGINAL ARTICLES
    5. ACKNOWLEDGEMENT OF REVIEWERS
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      Good guys from a shady family (pages 841–842)

      Natalia Gulyaeva and Victor Aniol

      Version of Record online: 8 JUN 2012 | DOI: 10.1111/j.1471-4159.2012.07708.x

  2. SHORT COMMUNICATIONS

    1. Top of page
    2. EDITORIAL HIGHLIGHT
    3. SHORT COMMUNICATIONS
    4. ORIGINAL ARTICLES
    5. ACKNOWLEDGEMENT OF REVIEWERS
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      Pcp4l1 contains an auto-inhibitory element that prevents its IQ motif from binding to calmodulin (pages 843–851)

      Marc A. J. Morgan and James I. Morgan

      Version of Record online: 27 APR 2012 | DOI: 10.1111/j.1471-4159.2012.07745.x

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      Here we characterize the biochemical properties of Purkinje cellprotein 4-like 1 (Pcp4l1) a small IQ motif protein closely related to the calmodulin regulators PEP-19 and neurogranin. We identify a motif within Pcp4l1 that prevents binding to calmodulin and through detailed mutagenesis identify isoleucine 36 as a critical residue for this inhibitory function. Collectively our experiments demonstrate an unexpected and previously uncharacterized mechanism for regulation of IQ motif to calmodulin binding.

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      Spatially restricted actin-regulatory signaling contributes to synapse morphology (pages 852–860)

      Daniel A. Nicholson, Michael E. Cahill, Christopher T. Tulisiak, Yuri Geinisman and Peter Penzes

      Version of Record online: 27 APR 2012 | DOI: 10.1111/j.1471-4159.2012.07743.x

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      An immuno-electron microscopy image showing a perforated post-synaptic density (PSD) in which kalirin-7 is exclusively localized extrasynaptically. Although kalirin-7 is known to regulate dendritic spine morphology, how its localization within individual spine domains contributes to the regulation of spine morphology is unknown. Using immuno-electron microscopy, we paradoxically find that increased expression of kalirin-7 extrasynaptically rather than synaptically is most directly related to synapse and spine size. These findings indicate that there are multiple kalirin-7 microdomains within spines that are likely to differentially influence spine morphology, and this study extends the current scientific knowledge of the spatial regulation of actin-regulatory molecules within individual spines.

  3. ORIGINAL ARTICLES

    1. Top of page
    2. EDITORIAL HIGHLIGHT
    3. SHORT COMMUNICATIONS
    4. ORIGINAL ARTICLES
    5. ACKNOWLEDGEMENT OF REVIEWERS
    1. Signal Transduction & Synaptic Transmission

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      Nesca, a novel neuronal adapter protein, links the molecular motor kinesin with the pre-synaptic membrane protein, syntaxin-1, in hippocampal neurons (pages 861–880)

      James I. S. MacDonald, Alfonso Dietrich, Sarah Gamble, Todd Hryciw, Robert Ian Grant and Susan O. Meakin

      Version of Record online: 2 APR 2012 | DOI: 10.1111/j.1471-4159.2012.07729.x

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      Nesca is a novel adapter protein that is exclusively expressed in the nervous system. Until now, however, a functional role for Nesca has been unknown. Using cell biology, confocal microscopy and in vitro-binding studies, we show that Nesca is a novel microtubule-binding protein, that it binds the kinesin motor KIF5 and the synaptic membrane precursor protein syntaxin-1. These studies suggest that Nesca serves a role, similar to syntabulin, in the anterograde transport of synaptic membrane precursor proteins essential to exocytosis.

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      A broadly tuned mouse odorant receptor that detects nitrotoluenes (pages 881–890)

      Jingyi Li, Rafi Haddad, Sisi Chen, Vanessa Santos and Charles W. Luetje

      Version of Record online: 19 APR 2012 | DOI: 10.1111/j.1471-4159.2012.07740.x

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      Smelling a bit of everything: A broadly tuned olfactory receptor The mammalian olfactory receptor repertoire is thought to include receptors with broad specificity. A mouse olfactory receptor is shown to be broadly tuned, recognizing chemical structures scattered across a large portion of odor space and yet making subtle distinctions among closely related structures. Understanding the molecular basis for such broad, yet discriminating, odorant recognition is a major challenge in olfaction.

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      Hypothermia-induced tyrosine phosphorylation of SIRPα in the brain (pages 891–902)

      Toshi Maruyama, Shinya Kusakari, Miho Sato-Hashimoto, Yuriko Hayashi, Takenori Kotani, Yoji Murata, Hideki Okazawa, Per-Arne Oldenborg, Shoji Kishi, Takashi Matozaki and Hiroshi Ohnishi

      Version of Record online: 24 APR 2012 | DOI: 10.1111/j.1471-4159.2012.07748.x

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      SIRPα is a membrane protein that undergoes tyrosine phosphorylation in the brain and is implicated in regulation of depression-like behavior in the forced swim test in cold water. We show that lowering the temperature in vivo and in vitro increased the level of tyrosine phosphorylation of SIRPα. Tyrosine phosphorylation of SIRPα is a novel cellular signal induced by low temperature.

    4. Brain Development & Cell Differentiation

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      Neuronal polarization is impaired in mice lacking RhoE expression (pages 903–914)

      Blanca Peris, Susana Gonzalez-Granero, Begoña Ballester-Lurbe, Jose-Manuel García-Verdugo, Ignacio Pérez-Roger, Consuelo Guerri, José Terrado and Rosa M. Guasch

      Version of Record online: 13 APR 2012 | DOI: 10.1111/j.1471-4159.2012.07733.x

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      Has RhoE/Rnd3 a role in neuronal development? Rnd proteins are important players in several aspects of brain development. Our results demonstrate that hippocampal neurons from a mice lacking RhoE expression exhibit a decrease in both neurite and axon outgrowth and also a delay in the process of neuronal polarization. We have also found that the RHOA/ROCK/LIMK/COFILIN pathway is involved in those alterations and its modulation may be very valuable to address neurodegenerative therapy.

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      A new agonist of the erythropoietin receptor, Epobis, induces neurite outgrowth and promotes neuronal survival (pages 915–923)

      Stanislava Pankratova, Bing Gu, Darya Kiryushko, Irina Korshunova, Lene B. Køhler, Mette Rathje, Elisabeth Bock and Vladimir Berezin

      Version of Record online: 24 APR 2012 | DOI: 10.1111/j.1471-4159.2012.07751.x

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      A novel functional agonist of the erythropoietin receptor with the potential to promote neuroregeneration and neuroprotectionErythropoietin (EPO) is a cytokine with both hematopoietic and neuroprotective properties, and the development of neuroprotective EPO mimetics lacking hematopoietic activity is an important issue. This study describes the identification and characterization of a novel agonist of the EPO receptor with neuritogenic and neuronal survival promoting properties. This finding has important implications for the development of treatments for neurodegenerative disorders.

    6. Neuronal Plasticity & Behavior

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      9-Methyl-β-carboline-induced cognitive enhancement is associated with elevated hippocampal dopamine levels and dendritic and synaptic proliferation (pages 924–931)

      Michael Gruss, Dorothea Appenroth, Armin Flubacher, Christoph Enzensperger, Jörg Bock, Christian Fleck, Gabriele Gille and Katharina Braun

      Version of Record online: 8 JUN 2012 | DOI: 10.1111/j.1471-4159.2012.07713.x

      Cognitive enhancement induced by 9-methyl-β-carboline The aim was to unveil a possible neurostimulatory effect of 9-me-BC within meso-limbo-cortical pathways. We found that 9-me-BC acts as cognitive enhancer and (i) improves spatial learning, (ii) elevates hippocampal dopamine levels and (iii) stimulates hippocampal dendritic and synaptic growth. This novel mechanism of 9-me-BC bears the potential for being applied to treat cognitive dysfunctions and neurodegenerative disorders.

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      Vitamin A deficiency impairs postnatal cognitive function via inhibition of neuronal calcium excitability in hippocampus (pages 932–943)

      Wei Jiang, Qin Yu, Min Gong, Li Chen, En Yi Wen, Yang Bi, Yun Zhang, Yuan Shi, Ping Qu, You Xue Liu, Xiao Ping Wei, Jie Chen and Ting Yu Li

      Version of Record online: 20 APR 2012 | DOI: 10.1111/j.1471-4159.2012.07697.x

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      Unravelling the mechanisms of memory in rats with Vitamin A deficiency Vitamin A deficiency (VAD) can cause learning and spatial memory deficits in rats. Most of the biological functions of vitamin A (VA) are mediated by retinoic acid (RA). We show that in VAD rats, long-term potentiation (LTP) was weak and NMDA-induced Ca2+ excitability in hippocampal CA1 neurons was suppressed compared to rats with normal VA levels. VAD rats also differed in retinoic acid receptor (RARα) mRNA and protein expression. Our data support the new idea that continuous postnatal VAD inhibits RARα expression, which decreases NR1 expression via no direct transcriptional regulation and then inhibits hippocampal neuronal Ca2+ excitability which affects LTP, finally producing deficits in active learning and spatial memory in adolescence.

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      Nerve injury increases brain-derived neurotrophic factor levels to suppress BK channel activity in primary sensory neurons (pages 944–953)

      Xue-Hong Cao, Shao-Rui Chen, Li Li and Hui-Lin Pan

      Version of Record online: 12 APR 2012 | DOI: 10.1111/j.1471-4159.2012.07736.x

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      Ca2+-activated K+ channels: a key regulator of pain-sensing neurons. Stimulation of Ca2+-activated K+ channels normally acts as a “brake” to restrain neurons’ firing activity. Nerve injury suppresses the activity of Ca2+-activated K+ channels in sensory neurons to facilitate pain transduction through a neurotrophic factor. The Ca2+-activated K+ channels represent a new target to treat nerve pain.

    9. Molecular Basis of Disease

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      Phosphoproteome profiling of substantia nigra and cortex regions of Alzheimer’s disease patients (pages 954–963)

      Saadia Zahid, Michael Oellerich, Abdul R Asif and Nikhat Ahmed

      Version of Record online: 24 APR 2012 | DOI: 10.1111/j.1471-4159.2012.07737.x

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      Aberrant phosphorylation and Alzheimer’s disease The molecular mechanisms underlying aberrant response to phosphorylation leading to AD pathology are not fully understood. The study facilitated the identification of nine proteins aberrantly phosphorylated in cortex and substantia nigra targeting cell metabolism, signal transduction, cytoskeletal integration and synaptic function. These findings may aid in developing effective therapeutic strategies and establishing broad database of potential proteins involved in AD.

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      Gain of function by phosphorylation in Presenilin 1-mediated regulation of insulin signaling (pages 964–973)

      Masato Maesako, Kengo Uemura, Akira Kuzuya, Kazuki Sasaki, Megumi Asada, Kiwamu Watanabe, Koichi Ando, Masakazu Kubota, Haruhiko Akiyama, Ryosuke Takahashi, Takeshi Kihara, Shun Shimohama and Ayae Kinoshita

      Version of Record online: 23 APR 2012 | DOI: 10.1111/j.1471-4159.2012.07741.x

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      The function of phosphorylated Presenilin 1 has not been elucidated. We demonstrate that phosphorylated Presenilin 1 at the serine 353 and 357 residues down-regulated the expression of insulin receptor compared with wild-type Presenilin 1, thus suggesting that phosphorylated PS1 may play the crucial role in a positive feed-forward cycle inhibiting insulin signaling. From our findings, insulin signaling dysfunction may be associated with the pathogenesis of Alzheimer disease.

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      Genetic depletion of brain 5HT reveals a common molecular pathway mediating compulsivity and impulsivity (pages 974–984)

      Mariana Angoa-Pérez, Michael J. Kane, Denise I. Briggs, Catherine E. Sykes, Mrudang M. Shah, Dina M. Francescutti, David R. Rosenberg, David M. Thomas and Donald M. Kuhn

      Version of Record online: 13 APR 2012 | DOI: 10.1111/j.1471-4159.2012.07739.x

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      Serotonin dysfunction has been implicated in a number of neuropsychiatric diseases such as depression and anxiety but its precise role in these disorders is poorly understood. In the present study, mice were genetically depleted of brain serotonin by knocking out the gene for tryptophan hydroxylase 2 and tested in numerous validated tests of behavioral disorders. Mice lacking brain serotonin are highly compulsive, impulsive and aggressive. These results indicate that brain serotonin mediates a common pathway of maladaptive behaviors that is best characterized as behavioral disinhibition.

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      Collapsin response mediator protein-2 phosphorylation promotes the reversible retraction of oligodendrocyte processes in response to non-lethal oxidative stress (pages 985–995)

      Agata Fernández-Gamba, María Celeste Leal, Chera L. Maarouf, Christiane Richter-Landsberg, Terence Wu, Laura Morelli, Alex E. Roher and Eduardo M. Castaño

      Version of Record online: 27 APR 2012 | DOI: 10.1111/j.1471-4159.2012.07742.x

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      Reactive oxygen species modulate oligodendroglial process extension The branching and extension of oligodendrocyte (OLG) processes, crucial for axon myelination, are regulated by extracellular signals. Yet, the role of reactive oxygen species (ROS) in such a dynamic mechanism is not known. Mild oxidative stress in mature OLG triggered a rapid process shortening mediated by phosphorylation of CRMP-2 by ROCK. We propose a novel level of process growth modulation by ROS that may help to understand early OLG dysfunction in neurodegeneration.

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      Modulation of gene expression during early stages of reconnection of the turtle spinal cord (pages 996–1006)

      Gabriela García, Gabriela Libisch, Omar Trujillo-Cenóz, Carlos Robello and Raúl E. Russo

      Version of Record online: 27 APR 2012 | DOI: 10.1111/j.1471-4159.2012.07750.x

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      Early mechanisms for endogenous repair of the injured spinal cordUnlike mammals, turtles display a substantial degree of endogenous repair after spinal cord injury. We find that brain lipid bind protein and connexin 43, but not Pax6 genes -active in multi-potent progenitors- are upregulated during early stages of regeneration. These findings suggest that progenitors react to injury by favoring the production of glia to support the navigation of regenerating axons. Immunohistochemistry for brain lipid binding protein (BLBP) in a stump of the spinal cord 4 days after complete transection.

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      A natural coumarin derivative esculetin offers neuroprotection on cerebral ischemia/reperfusion injury in mice (pages 1007–1013)

      Chen Wang, Aijie Pei, Jing Chen, Hailong Yu, Mei-Ling Sun, Chun-Feng Liu and Xingshun Xu

      Version of Record online: 8 JUN 2012 | DOI: 10.1111/j.1471-4159.2012.07744.x

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      Although evidences have demonstrated that a natural coumarin compound esculetin rescues primary neurons from NMDA toxicity, it is unclear whether esculetin has neuroprotective effects on cerebral ischemia/reperfusion injury in vivo. By using a middle cerebral artery occlusion mouse model, we found that either pre-treatment or post-treatment of esculetin reduced infarct volume and improved neurological deficits. Our finding indicates that esculetin has a therapeutic potential for the treatment of stroke in the future clinical trials.

  4. ACKNOWLEDGEMENT OF REVIEWERS

    1. Top of page
    2. EDITORIAL HIGHLIGHT
    3. SHORT COMMUNICATIONS
    4. ORIGINAL ARTICLES
    5. ACKNOWLEDGEMENT OF REVIEWERS
    1. You have free access to this content
      Acknowledgement of Reviewers (pages 1014–1016)

      Version of Record online: 8 JUN 2012 | DOI: 10.1111/j.1471-4159.2011.07776.x

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