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Journal of Neurochemistry

Cover image for Vol. 123 Issue 4

November 2012

Volume 123, Issue 4

Pages 459–645

  1. SHORT COMMUNICATIONS

    1. Top of page
    2. SHORT COMMUNICATIONS
    3. ORIGINAL ARTICLES
    4. CORRIGENDUM
    1. You have full text access to this OnlineOpen article
      Primary microRNA precursor transcripts are localized at post-synaptic densities in adult mouse forebrain (pages 459–466)

      Giovanni Lugli, John Larson, Michael P. Demars and Neil R. Smalheiser

      Article first published online: 28 SEP 2012 | DOI: 10.1111/j.1471-4159.2012.07921.x

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      MicroRNA Processing: A Surprise at Synapses

      It has generally been thought that transcription of microRNA genes occurs via production of long primary gene transcripts (pri-miRs), which are processed within the nucleus by a drosha/DGCR8 complex to form small hairpin precursors (pre-miRs) that are exported to the cytoplasm and processed by dicer to form mature miRNAs. However, we show here that a variety of pri-miRs as well as a substantial portion of drosha and DGCR8 are found outside the nucleus and are strongly associated with post-synaptic densities (PSDs) and RNA transport complexes in adult mouse forebrain. Together with previous studies showing that dicer is also enriched at PSDs and activated by synaptic activation, this suggests that the entire miRNA biogenesis machinery is expressed locally near synapses, may be regulated by local signaling events, and may account for at least a portion of the mature miRNAs present within dendrites.

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      Brain region-specific immunolocalization of the lipolysis-stimulated lipoprotein receptor (LSR) and altered cholesterol distribution in aged LSR+/− mice (pages 467–476)

      Christophe Stenger, Anthony Pinçon, Marine Hanse, Laurent Royer, Audrey Comte, Violette Koziel, Jean-Luc Olivier, Thierry Pillot and Frances T. Yen

      Article first published online: 28 SEP 2012 | DOI: 10.1111/j.1471-4159.2012.07922.x

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      Mouse brain expression of the lipolysis-stimulated lipoprotein receptor (LSR) and its potential role in regulating brain cholesterol homeostasis. Lipid homeostasis plays an important role in maintaining proper brain neuronal function and cognition. LSR is expressed in the neurons of specific brain regions and 18-month-old LSR+/− mice demonstrate modified brain cholesterol distribution and decreased latency in the Y-maze paradigm. These results suggest an important role for this receptor in the regulation of brain cholesterol distribution, which is important in preserving neuronal integrity and thereby cognitive functions during aging.

  2. ORIGINAL ARTICLES

    1. Top of page
    2. SHORT COMMUNICATIONS
    3. ORIGINAL ARTICLES
    4. CORRIGENDUM
    1. Gene Regulation & Genetics

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      Interrogation of brain miRNA and mRNA expression profiles reveals a molecular regulatory network that is perturbed by mutant huntingtin (pages 477–490)

      Jing Jin, Yong Cheng, Yongqing Zhang, William Wood, Qi Peng, Emmette Hutchison, Mark P. Mattson, Kevin G. Becker and Wenzhen Duan

      Article first published online: 28 SEP 2012 | DOI: 10.1111/j.1471-4159.2012.07925.x

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      Interrogation of brain miRNA and mRNA expression profiles reveals a molecular regulatory network that is perturbed by mutant huntingtin

      We performed miRNA array analysis combined with mRNA profiling in the brain of Huntington's disease (HD) mice to identify the individual miRNAs that are altered in HD and may therefore regulate a gene network underlying mutant huntingtin-induced neuronal dysfunction in HD. We revealed a significant alteration of miR-200 family members in the cerebral cortex and the striatum, at the early stage of disease progression in HD mice. Our results suggest that altered expression of miR-200 may interrupt the production of proteins involved in neuronal plasticity and survival, and provide insight into novel therapeutic approaches for HD.

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      Induction of P-glycoprotein and Bcrp at the rat blood–brain barrier following a subchronic morphine treatment is mediated through NMDA/COX-2 activation (pages 491–503)

      Salah Yousif, Catarina Chaves, Sophie Potin, Isabelle Margaill, Jean-Michel Scherrmann and Xavier Declèves

      Article first published online: 3 SEP 2012 | DOI: 10.1111/j.1471-4159.2012.07890.x

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      Subchronic morphine treatment induces P-glycoprotein and Bcrp up-regulation at the blood-brain barrier. However, morphine may not directly stimulate P-gp and Bcrp expression in brain endothelial cells, and it is more likely that the glutamate released during morphine withdrawal may be responsible for this up-regulation, through subsequent activation of NMDA receptors and COX-2 activity.

    3. Signal Transduction & Synaptic Transmission

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      Expression and functional properties of α7 acetylcholine nicotinic receptors are modified in the presence of other receptor subunits (pages 504–514)

      Manuel Criado, Luis M. Valor, José Mulet, Susana Gerber, Salvador Sala and Francisco Sala

      Article first published online: 28 SEP 2012 | DOI: 10.1111/j.1471-4159.2012.07931.x

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      α7 nicotinic receptor subunits interact with other subunits: Although α7 nicotinic receptors are predominantly homopentamers, assembly of them with other subunits was studied. As a consequence, expression of functional receptors decreased and heteromeric receptors made of α7 and β4 subunits were detected at the cell membrane. The association of α7 with other nicotinic receptor subunits suggests the possibility of non-conventional α7 responses.

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      The N-terminal domain of the myelin enzyme 2′,3′-cyclic nucleotide 3′-phosphodiesterase: direct molecular interaction with the calcium sensor calmodulin (pages 515–524)

      Matti Myllykoski, Kouichi Itoh, Salla M. Kangas, Anthony M. Heape, Sung-Ung Kang, Gert Lubec, Inari Kursula and Petri Kursula

      Article first published online: 28 SEP 2012 | DOI: 10.1111/jnc.12000

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      The N-terminal domain of the myelin enzyme CNPase binds calmodulin

      The membrane-associated enzyme 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) is one of the most abundant proteins in the myelin sheath. In this study, we show that the CNPase N-terminal domain interacts directly with the ubiquitous calcium sensor protein calmodulin. Our finding implies that the function of CNPase, which is currently poorly understood, could be regulated by cellular calcium levels.

    5. Bioenergetics & Metabolism

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      High-energy compounds promote physiological processing of Alzheimer's amyloid-β precursor protein and boost cell survival in culture (pages 525–531)

      Darrell R. Sawmiller, Huey T. Nguyen, Olga Markov and Ming Chen

      Article first published online: 21 SEP 2012 | DOI: 10.1111/j.1471-4159.2012.07923.x

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      High-energy compounds are potential medications for Alzheimer's disease (AD)

      Energy crisis underlies brain aging and AD, so boosting energy would be an ideal point of entry for intervention. We found that high-energy compounds (e.g., ATP and phosphoenol pyruvate) robustly promoted APP normal processing and also boosted cells’ resilience against energy crisis and oxidative stress, thus they can be potential medications for AD. The figure shows that phosphoenol pyruvate (PEP) protected cultured SH-SY5Y neurons against the impairments of rotenone (Rot), an energy metabolic inhibitor.

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      Altered neurochemical profile in the McGill-R-Thy1-APP rat model of Alzheimer's disease: a longitudinal in vivo 1H MRS study (pages 532–541)

      Linn H. Nilsen, Torun M. Melø, Oddbjørn Sæther, Menno P. Witter and Ursula Sonnewald

      Article first published online: 1 OCT 2012 | DOI: 10.1111/jnc.12003

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      The study of transgenic animals is instrumental to achieve a better understanding of early aspects of Alzheimer's disease. We found prominent metabolite alterations at the pre-plaque stage of 3 months and also during the progression of AD pathology in McGill-R-Thy1-APP rats. The findings demonstrate that in vivo 1H MRS is a powerful tool to investigate disease-related metabolite changes in brain.

    7. Neuroinflammation & Neuroimmunology

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      Over-expression of HSP70 attenuates caspase-dependent and caspase-independent pathways and inhibits neuronal apoptosis (pages 542–554)

      Boris Sabirzhanov, Bogdan A. Stoica, Marie Hanscom, Chun-Shu Piao and Alan I. Faden

      Article first published online: 28 SEP 2012 | DOI: 10.1111/j.1471-4159.2012.07927.x

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      HSP70 over-expression protects against multiple models of cell death, however, the role of HSP70 in neuronal apoptosis is not well investigated. We demonstrated using multiple models of apoptosis that HSP70 over-expression significantly reduced neuronal cell death at least in part by binding and potentially inactivating Apoptotic protease-activating factor 1 and apoptosis-inducing factor. These data suggest that HSP70 can inhibit both caspase-dependent and caspase-independent neuronal apoptosis pathways.

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      Acetate reduces microglia inflammatory signaling in vitro (pages 555–567)

      Mahmoud L. Soliman, Kendra L. Puig, Colin K. Combs and Thad A. Rosenberger

      Article first published online: 28 SEP 2012 | DOI: 10.1111/j.1471-4159.2012.07955.x

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      Acetylation of histone and non-histone proteins reduce inflammatory signaling in microglia

      Acetate supplementation attenuates neuroinflammation by reducing neuroglia activation and IL-1β release in vivo. We demonstrate that acetate metabolism in cultured microglia modulates cytokine balance to a more anti-inflammatory state by a mechanism that involves the acetylation of both histone and non-histone proteins. These data suggest that increasing acetate metabolism in microglia can reduce inflammatory phenotype by epigenetic and non-epigenetic mechanisms.

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      Novel cerebrospinal fluid and serum autoantibody targets for clinically isolated syndrome (pages 568–577)

      Myrthe Rouwette, Klaartje Somers, Cindy Govarts, Peter P. De Deyn, Raymond Hupperts, Bart Van Wijmeersch, Brigit A. De Jong, Marcel M. Verbeek, Vincent Van Pesch, Christian Sindic, Luisa M. Villar, José C. Álvarez-Cermeño, Piet Stinissen and Veerle Somers

      Article first published online: 28 SEP 2012 | DOI: 10.1111/jnc.12005

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      Clinically isolated syndrome (CIS) is a possible first manifestation of multiple sclerosis (MS) and limited information is available on the identity of antigens targeted by antibodies in CIS. We applied a phage display technique and identified a panel of six novel candidate antigens, to which both cerebrospinal fluid and serum antibody reactivity could be detected in CIS and MS. Moreover, prognostic potential to predict conversion to MS in CIS patients could be demonstrated for two antigens.

    10. Neuronal Plasticity & Behavior

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      Adolescent rats are resistant to adaptations in excitatory and inhibitory mechanisms that modulate mesolimbic dopamine during nicotine withdrawal (pages 578–588)

      Luis A. Natividad, Matthew W. Buczynski, Loren H. Parsons, Oscar V. Torres and Laura E. O'Dell

      Article first published online: 1 OCT 2012 | DOI: 10.1111/j.1471-4159.2012.07926.x

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      Insights into the neurochemical mechanisms mediating enhanced vulnerability to tobacco abuse during adolescence

      One factor contributing to tobacco abuse is relapse produced by withdrawal. This study revealed that withdrawal decreases mesolimbic dopamine via amino acid regulation within the cell body region of this pathway. Interestingly, adolescents were insensitive to these effects. Our findings provide a mechanism of developmental differences in withdrawal and they suggest that treatments focused on alleviating withdrawal may be less effective in adolescents.

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      Ca++/CaMKII switches nociceptor-sensitizing stimuli into desensitizing stimuli (pages 589–601)

      Tim Hucho, Vanessa Suckow, Elizabeth K. Joseph, Julia Kuhn, Jan Schmoranzer, Olayinka A. Dina, Xiaojie Chen, Matthias Karst, Michael Bernateck, Jon D. Levine and Hans-Hilger Ropers

      Article first published online: 28 SEP 2012 | DOI: 10.1111/j.1471-4159.2012.07920.x

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      Rerouting of Pain Signaling Regulation of intracellular signaling pathways mostly modifies gradually the signaling amplitude from ON to OFF. We now describe an alternative regulation: signaling rerouting. Thereby, pain sensitizing stimuli still activate signaling. But instead of sensitization they result in desensitization. Such reprogramming of signaling pathways could be an interesting novel therapeutic approach in contrast to classical pain blockers.

    12. Molecular Basis of Disease

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      Ethanol disrupts axon outgrowth stimulated by netrin-1, GDNF, and L1 by blocking their convergent activation of Src family kinase signaling (pages 602–612)

      Suzhen Chen and Michael E. Charness

      Article first published online: 28 SEP 2012 | DOI: 10.1111/j.1471-4159.2012.07954.x

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      Src family kinase signaling is a critical target in alcohol disruption of neuronal differentiation.

      The molecule mechanisms that underlie fetal alcohol spectrum disorders remain unclear. Alcohol inhibits axon outgrowth mediated by netrin-1, GDNF, and L1 in cerebellar granule neurons by blocking their activation of the Src family kinase-Cas-ERK1/2 signaling pathway. Our observations suggest that actions of alcohol at a single locus can disrupt the regulation of brain development by multiple, developmentally critical molecules.

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      Early mitochondrial abnormalities in hippocampal neurons cultured from Fmr1 pre-mutation mouse model: (pages 613–621)

      Eitan S. Kaplan, Zhengyu Cao, Susan Hulsizer, Flora Tassone, Robert F. Berman, Paul J. Hagerman and Isaac N. Pessah

      Article first published online: 28 SEP 2012 | DOI: 10.1111/j.1471-4159.2012.07936.x

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      Pre-mutation carriers of a trinucleotide (pre-CGG) expansion of the fragile-X mental retardation 1 (FMR1) gene can display a range of clinical features that include behavioral and cognitive abnormalities in children, primary ovarian insufficiency, and fragile-X-associated tremor/ataxia syndrome (FXTAS). We demonstrate that in pre-CGG KI mice, hippocampal neuronal neurites have significantly decreased mitochondrial density and mobility as well as aberrant metabolic function, as early as 4 days in vitro. We conclude that deficits in mitochondrial trafficking and metabolic function occur as a consequence of over-expression of Fmr1 mRNA, although the moderate reductions of FMRP also may play a role.

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      Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism (pages 622–634)

      Hugo Gonzalo, Luis Brieva, Franz Tatzber, Mariona Jové, Daniel Cacabelos, Anna Cassanyé, Lucia Lanau-Angulo, Jordi Boada, José C. E. Serrano, Cristina González, Lourdes Hernández, Sílvia Peralta, Reinald Pamplona and Manuel Portero-Otin

      Article first published online: 28 SEP 2012 | DOI: 10.1111/j.1471-4159.2012.07934.x

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      A wrong response against wrong lipids: lipid peroxidation autoantibodies in multiple sclerosis. This study was aimed at obtaining a metabolomic and lipidomic fingerprint of multiple sclerosis. The results reveal both increased and specific lipid peroxidation in this disease, which is associated to the presence of autoantibodies against proteins modified with lipid peroxidation. This data uncovers a potential novel, lipid-peroxidation based, autoimmune response in multiple sclerosis pathophysiology

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      Age-related differences in the dynamics of hippocampal proteasome recovery (pages 635–644)

      M. Paz Gavilán, Cristina Pintado, Elena Gavilán, Luisa M. García-Cuervo, Angelica Castaño, Rosa M. Ríos and Diego Ruano

      Article first published online: 1 OCT 2012 | DOI: 10.1111/j.1471-4159.2012.07932.x

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      Proteasome regulation is critical to hippocampal homeostasis. Here, we show that young rats strongly increase the biogenesis of constitutive proteasomes, whereas aged rats moderately increase the biogenesis of immunoproteasome. Proteasome inhibition highly affected pyramidal cells, leading to the accumulation of ubiquitinated proteins in perinuclear regions of aged, but not young pyramidal neurons. The lower capacity to maintain proteasome homeostasis could represent an additional factor contributing to hippocampal neurodegeneration.

  3. CORRIGENDUM

    1. Top of page
    2. SHORT COMMUNICATIONS
    3. ORIGINAL ARTICLES
    4. CORRIGENDUM
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