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Journal of Neurochemistry

Cover image for Vol. 123 Issue 5

December 2012

Volume 123, Issue 5

Pages 647–896

  1. EDITORIAL HIGHLIGHT

    1. Top of page
    2. EDITORIAL HIGHLIGHT
    3. REVIEW
    4. SHORT COMMUNICATIONS
    5. ORIGINAL ARTICLES
    6. OBITUARY
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      Current status of vaccination therapies in Alzheimer's disease (pages 647–651)

      Eric Karran

      Article first published online: 11 OCT 2012 | DOI: 10.1111/jnc.12009

      The failure of two monoclonal antibodies, bapineuzumab and solanezumab, to meet their primary end point measures in phase 3 clinical testing for mild-to-moderate Alzheimer's disease (AD) is a serious blow to the field. These drugs were targeting the Abeta peptide, as were three previous drugs that also failed to meet their primary end points. These findings will call into question the role that Abeta plays in AD and will also provoke much circumspection in ‘big pharma’ as to whether they can continue to invest in clinical research in such an intractable disease. However, there is much data yet to be published on these trials and a careful analysis, and cross-comparison of all of the data may well provide insights that will take the field closer to the phase 3 clinical success that is desperately needed by patients and healthcare providers worldwide. Although these failures are disappointing, now is not the time to falter in our pursuit of medicines for this devastating disease.

  2. REVIEW

    1. Top of page
    2. EDITORIAL HIGHLIGHT
    3. REVIEW
    4. SHORT COMMUNICATIONS
    5. ORIGINAL ARTICLES
    6. OBITUARY
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  3. SHORT COMMUNICATIONS

    1. Top of page
    2. EDITORIAL HIGHLIGHT
    3. REVIEW
    4. SHORT COMMUNICATIONS
    5. ORIGINAL ARTICLES
    6. OBITUARY
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      Epineurial adipocytes are dispensable for Schwann cell myelination (pages 662–667)

      Karim Nadra, Jean-Jacques Médard, Laure Quignodon, Mark H. G. Verheijen, Béatrice Desvergne and Roman Chrast

      Article first published online: 10 OCT 2012 | DOI: 10.1111/j.1471-4159.2012.07896.x

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      The absence of functional epineurial adipocytes does not affect myelination.It was previously suggested that epineurial adipocytes might play a role in peripheral nervous system myelination. Our characterization of two knockout mice models revealed that the absence of functional epineurial adipocytes does not lead to detectable defects in Schwann cell myelination. These data indicate that the presence of adipocytes in epineurium is dispensable for establishment or maintenance of proper myelin.

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      Microwave irradiation decreases ATP, increases free [Mg2+], and alters in vivo intracellular reactions in rat brain (pages 668–675)

      Shireesh Srivastava, Yoshihiro Kashiwaya, Xuesong Chen, Jonathan D. Geiger, Robert Pawlosky and Richard L. Veech

      Article first published online: 7 NOV 2012 | DOI: 10.1111/jnc.12026

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      The brain energy profile is distorted by microwave radiation

      Because microwave radiation has gained increasing acceptance for brain tissue fixation, the concentrations of a broad range of biochemical intermediates from irradiated tissue were compared to that of freeze-blown brain tissue. Radiation reduced [ATP] and increased [ADP] coinciding with higher levels of intracellular free Mg2+, which gave rise to a novel energetic state. A change to the [Mg2+] modifies selected enzyme rate constants, which distort energy determinants in microwaved brains.

  4. ORIGINAL ARTICLES

    1. Top of page
    2. EDITORIAL HIGHLIGHT
    3. REVIEW
    4. SHORT COMMUNICATIONS
    5. ORIGINAL ARTICLES
    6. OBITUARY
    1. Signal Transduction & Synaptic Transmission

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      Mitogen- and stress-activated kinases regulate progenitor cell proliferation and neuron development in the adult dentate gyrus (pages 676–688)

      Yun-Sik Choi, Kate Karelina, Diego Alzate-Correa, Kari R. Hoyt, Soren Impey, J. Simon Arthur and Karl Obrietan

      Article first published online: 25 OCT 2012 | DOI: 10.1111/jnc.12035

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      Throughout life, the subgranular zone (SGZ) neurogenic niche seeds the dentate gyrus with new neurons. In this study we examined the role of the ERK/MAPK effectors mitogen-stress activated kinases 1 and 2 (MSK1/2) in SGZ progenitor cell proliferation and neuron morphological maturation. The data presented here indicate that MSK1/2 play key roles in regulating basal and inducible SGZ progenitor proliferation as well as regulating the morphological maturation of adult-born neurons.

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      Decreases in plasma membrane Ca2+-ATPase in brain synaptic membrane rafts from aged rats (pages 689–699)

      Lei Jiang, Misty D. Bechtel, Nadezhda A. Galeva, Todd D. Williams, Elias K. Michaelis and Mary L. Michaelis

      Article first published online: 11 OCT 2012 | DOI: 10.1111/j.1471-4159.2012.07918.x

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      The aging synapse: Ca2+ pumps and rafts

      Dysregulation of Ca2+ homeostasis is associated with brain aging and loss of membrane Ca2+ pumping activity is one contributor. We found the highest synaptic membrane Ca2+ pumping activity in the lipid rafts and the greatest loss with age in raft domains. Significant localization of the pump within rafts suggests the lipid environment may strongly influence its activity in aging brain.

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      Importance of cholesterol in dopamine transporter function (pages 700–715)

      Kymry T. Jones, Juan Zhen and Maarten E. A. Reith

      Article first published online: 11 OCT 2012 | DOI: 10.1111/jnc.12007

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      The influence of cholesterol on substrate efflux by the dopamine transporter (DAT) is poorly understood. We provide evidence that DA efflux by DAT at resting membrane potential for a large part depends on direct cholesterol–DAT interactions, as does DA uptake by DAT. Our results suggest the importance of cholesterol rather than raft localization of DAT in regulating DA uptake and release.

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      Role of glycosphingolipids in the function of human serotonin1A receptors (pages 716–724)

      Pushpendra Singh, Yamuna Devi Paila and Amitabha Chattopadhyay

      Article first published online: 11 OCT 2012 | DOI: 10.1111/jnc.12008

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      This study was performed to understand the role of glycosphingolipids in the function of serotonin1A receptors. Our results show that glycosphingolipid depletion results in impairment of function of the serotonin1A receptor. These results could be useful in understanding the role of glycosphingolipids in the function of the serotonin1A receptor in particular, and GPCRs in general.

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      Mass spectrometry analysis of human P2X1 receptors; insight into phosphorylation, modelling and conformational changes (pages 725–735)

      Jonathan A. Roberts, Andrew R. Bottrill, Sharad Mistry and Richard J. Evans

      Article first published online: 11 OCT 2012 | DOI: 10.1111/jnc.12012

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      Mapping movement and phosphorylation of human P2X1 receptors

      Mass spectroscopic analysis of purified P2X1 receptors was used to gain insight into receptor phosphorylation and conformational changes. The P2X1 was basally phosphorylated at three positions and cross-linking adjacent receptor subunits inhibited function. The basal phosphorylation was not essential for normal function however significant movement was required in the extracellular domain for receptor activation.

    6. Neuroinflammation & Neuroimmunology

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      Nitric oxide-mediated regulation of β-amyloid clearance via alterations of MMP-9/TIMP-1 (pages 736–749)

      Lisa A. Ridnour, Sneha Dhanapal, Michael Hoos, Joan Wilson, Jennifer Lee, Robert Y. S. Cheng, Ernst E. Brueggemann, Harry B. Hines, Donna M. Wilcock, Michael P. Vitek, David A. Wink and Carol A. Colton

      Article first published online: 25 OCT 2012 | DOI: 10.1111/jnc.12028

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      Nitric Oxide-Mediated Regulation of β-Amyloid Clearance via Alterations of MMP-9/TIMP-1

      The balance between production and degradation of Abeta proteins is critical to amyloid accumulation and ensuing disease. Fibrillar Abeta is digested to less toxic products by proteolytic enzymes including MMP-9. Our in vitro and in vivo data show that nitric oxide regulates both MMP-9 and its endogenous inhibitor TIMP-1. Thus Abeta degradation and clearance are controlled by MMP9/TIMP1 ratio in an NO-dependent manner.

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      Role of the blood–cerebrospinal fluid barrier transporter as a cerebral clearance system for prostaglandin E2 produced in the brain (pages 750–760)

      Masanori Tachikawa, Go Ozeki, Takanori Higuchi, Shin-ichi Akanuma, Kazuhiro Tsuji and Ken-ichi Hosoya

      Article first published online: 10 OCT 2012 | DOI: 10.1111/jnc.12018

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      An imbalance in the rates of production and clearance of prostaglandin (PG) E2 under pathological conditions appears to affect the concentration of PGE2 in the CSF. This study demonstrated that microsomal PGE synthetase-1 (mPGES-1) is expressed in the pia mater and astrocytes, and a regulatory system for the PGE2 level in the CSF involves OAT3-mediated PGE2 uptake by choroid plexus epithelial cells. The findings provide a novel insight into the production and clearance of PGE2 in the CSF.

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      Activation of the P2X7 receptor induces migration of glial cells by inducing cathepsin B degradation of tissue inhibitor of metalloproteinase 1 (pages 761–770)

      Niamh Murphy and Marina A. Lynch

      Article first published online: 25 OCT 2012 | DOI: 10.1111/jnc.12031

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      P2X7 receptors induce neuroinflammatory changes associated with several neurological conditions. Activation of P2X7 receptors resulted in cathepsin B release, decreased TIMP-1, activation of MMP-9 and cell migration. Activation of the P2X7 receptor induces cell migration by effecting cathepsin B degradation of TIMP-1 and activation of MMP-9. Targeting this pathway may provide novel pharmacological tools to enable repair in many neurological disorders.

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      A comprehensive study on long-term injury to nigral dopaminergic neurons following intracerebroventricular injection of lipopolysaccharide in rats (pages 771–780)

      Yan Zhou, Yanxin Zhang, Junquan Li, Fengyue Lv, Yongmei Zhao, Deyi Duan and Qunyuan Xu

      Article first published online: 25 OCT 2012 | DOI: 10.1111/jnc.12010

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      Long-term selective injury to DA neurons

      To create a new rat model for mimicking better pathogenesis of PD, a single intracerebroventricular injection of LPS was made, and a series of assays were done after injection for a long-term. It is shown clearly a selective and progressive injury to DA neurons through a long-term inflammation in the brain, indicating this model is useful for further research of human PD.

    10. Neuronal Plasticity & Behavior

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      Long-term perturbation of spine plasticity results in distinct impairments of cognitive function (pages 781–789)

      Jon-Eric VanLeeuwen and Peter Penzes

      Article first published online: 11 OCT 2012 | DOI: 10.1111/j.1471-4159.2012.07899.x

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      Long-term perturbation of spine plasticity results in distinct impairments of cognitive function

      Using genetically modified mice deficient in a central regulator of spine plasticity, we investigated the brain region-specific contribution of spine numbers to various cognitive functions. We found distinct cognitive functions display differential sensitivity to spine loss in the cortex and hippocampus. Our data support spines as neuronal structures important for cognition and suggest interplay between brain regions is critical for complex cognitive processing.

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      Transcriptome analysis of long non-coding RNAs of the nucleus accumbens in cocaine-conditioned mice (pages 790–799)

      Qian Bu, Zhengtao Hu, Feng Chen, Ruiming Zhu, Yi Deng, Xue Shao, Yan Li, Jinxuan Zhao, Hongyu Li, Baolai Zhang, Lei Lv, Guangyan Yan, Yinglan Zhao and Xiaobo Cen

      Article first published online: 25 OCT 2012 | DOI: 10.1111/jnc.12006

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      Cocaine Modifies Transcriptional Profiling of lncRNAs

      LncRNAhas been shown to be involved in various neurological diseases;however, itsrole in drug addiction is unknown. Here, we identified 603 lncRNAs changed significantly in brain nucleus accunbens of cocaine-dependent mice, providing 48 pair mRNA-lncRNAs significantly modified. These findings provide for the first time new insights intothepotentialinvolvement of lncRNAs in neuroplasticity and drug addiction.

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      Elevated expression of brain-derived neurotrophic factor facilitates visual imprinting in chicks (pages 800–810)

      Keiko Suzuki, Fumihiko Maekawa, Shingo Suzuki, Tomoharu Nakamori, Hayato Sugiyama, Tomoyuki Kanamatsu, Kohichi Tanaka and Hiroko Ohki-Hamazaki

      Article first published online: 25 OCT 2012 | DOI: 10.1111/jnc.12039

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      BDNF facilitates imprinting behavior in chicks

      BDNF is one of the plasticity related molecules and implicated in learning and memory. Here we studied its role in imprinting, an ideal model of juvenile learning. Expression of BDNF is enhanced during the critical period, increased upon imprinting learning, and BDNF injection in HDCo, a center of visual imprinting, facilitates memory formation. These results suggest that BDNF regulates learning efficiency in early childhood.

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      Pharmacological or genetic blockade of the dopamine D3 receptor increases cell proliferation in the hippocampus of adult mice (pages 811–823)

      Martin Egeland, Xiaoqun Zhang, Mark J. Millan, Elisabeth Mocaer and Per Svenningsson

      Article first published online: 10 OCT 2012 | DOI: 10.1111/jnc.12011

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      Conflicting data in literature regarding the role of dopamine in the regulation of adult neurogenesis suggest that several receptors may be involved. In this study, data from both pharmacological and genetic modulation experiments indicate that the D3 receptor acts to inhibit cell proliferation in the hippocampus. This study indicates that the D3 receptor may be an interesting target with which to regulate adult hippocampal neurogenesis.

    14. Molecular Basis of Disease

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      High levels of Mn2+ inhibit secretory pathway Ca2+/Mn2+-ATPase (SPCA) activity and cause Golgi fragmentation in neurons and glia (pages 824–836)

      M. Rosario Sepúlveda, Frank Wuytack and Ana M. Mata

      Article first published online: 3 SEP 2012 | DOI: 10.1111/j.1471-4159.2012.07888.x

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      Manganese is an essential trace element, but in excess can be neurotoxic. Mn2+ overload compromises survival of neurons and glia in primary cultures specifically affecting Golgi organization. Golgi houses the Ca2+/Mn2+-ATPase SPCA, whose activity is inhibited by high Mn2+ levels. Glia is more resistant to Mn2+ toxicity than neurons and provides some protection against neurodegeneration. Furthermore, Mn2+ effects could be reversed upon Mn2+ removal.

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      Pen-2 is dispensable for endoproteolysis of presenilin 1, and nicastrin-Aph subcomplex is important for both γ-secretase assembly and substrate recruitment (pages 837–844)

      Guozhang Mao, Mei-Zhen Cui, Tong Li, Yipeng Jin and Xuemin Xu

      Article first published online: 11 OCT 2012 | DOI: 10.1111/jnc.12016

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      Pen-2 is dispensable for endoproteolysis of presenilin 1, and nicastrin-Aph subcomplex is important for both γ-secretase assembly and substrate recruitment.

      There are still questions remaining unanswered regarding the role of each component of the γ-secretase complex during its maturation and interaction with APP. The most relevant, novel finding of this study is that Pen-2 is dispensable for presenilin endoproteolysis, and the nicastrin-Aph subcomplex is important for γ-secretase assembly and substrate recruitment. This information is critical for understanding how γ-secretase catalyzes APP processing and Aβ formation.

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      Disruption of subcellular Arc/Arg 3.1 mRNA expression in striatal efferent neurons following partial monoamine loss induced by methamphetamine (pages 845–855)

      Melissa L. Barker-Haliski, Katharina Oldenburger and Kristen A. Keefe

      Article first published online: 10 OCT 2012 | DOI: 10.1111/jnc.12017

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      Methamphetamine-induced neurotoxicity disrupts Arc expression underlying consolidation of striatally-based learning; however, whether METH-induced neurotoxicity disrupts Arc transcription or trafficking is unknown. We now demonstrate that basal Arc transcription and cytoplasmic expression are elevated, but behaviorally-induced transcriptional activation of Arc is abolished in METH-pretreated rats. These results suggest that Arc or factors regulating it could be targets for addressing METH-induced cognitive impairments.

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      Asp664 cleavage of amyloid precursor protein induces tau phosphorylation by decreasing protein phosphatase 2A activity (pages 856–865)

      Seok Soon Park, Hyun-Jung Jung, Yoon-Jeong Kim, Tae Kwan Park, Chaeyoung Kim, Heesun Choi, In Hee Mook-Jung, Edward H. Koo and Sun Ah Park

      Article first published online: 25 OCT 2012 | DOI: 10.1111/jnc.12032

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      Caspase activation is known to be important in mediating Alzheimer's pathology. Here, we found that C-terminal fragment of APP released by caspase cleavage directly interact with PP2A thereby increasing tau phosphorylation. This event intimately connected with Aβ which enhances caspase cleavage. Our results suggest that caspase cleavage of APP plays a role as a mediator of Aβ-induced tau pathology.

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      Transcriptional suppression of the neuronal PAS domain 4 (Npas4) gene by stress via the binding of agonist-bound glucocorticoid receptor to its promoter (pages 866–875)

      Yoko Furukawa-Hibi, Jaesuk Yun, Taku Nagai and Kiyofumi Yamada

      Article first published online: 25 OCT 2012 | DOI: 10.1111/jnc.12034

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      Glucocorticoid reduced Npas4 promoter activity via the negative GRE, while restraint stress increased the binding of ligand-associated GR to Npas4 promoter in the hippocampus. Our findings suggest that transcription of Npas4 is down-regulated by stress via the binding of GR to its promoter.

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      Neuroprotection by urate on 6-OHDA-lesioned rat model of Parkinson's disease: linking to Akt/GSK3β signaling pathway (pages 876–885)

      Li Gong, Qi-Lin Zhang, Ning Zhang, Wen-Yan Hua, Yi-Xian Huang, Ping-Wei Di, Tingting Huang, Xing-Shun Xu, Chun-Feng Liu, Li-Fang Hu and Wei-Feng Luo

      Article first published online: 25 OCT 2012 | DOI: 10.1111/jnc.12038

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      Neuroprotection by urate on 6-OHDA-lesioned rats

      Urate has emerged as a promising target for PD therapy; however, this lacks in vivo experimental evidence. Systemic treatment with uric acid elevated plasma and brain urate levels and protected nigrostriatal neurons by regulating Akt/GSK3β signaling. It is the first in vivo demonstration of urate's neuroprotection in PD model and has high translational significance. Systemic treatment with uric acid elevated urate levels in both plasma and striatum, and protected dopaminergic neurons and terminals in substantia nigra and striatum in unilaterally striatal 6-OHDA-lesioned rats, as compared to vehicle-treated group.

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      A complex of synaptic adhesion molecule CADM1, a molecule related to autism spectrum disorder, with MUPP1 in the cerebellum (pages 886–894)

      Eriko Fujita, Yuko Tanabe, Beat A. Imhof, Mariko Y. Momoi and Takashi Momoi

      Article first published online: 10 OCT 2012 | DOI: 10.1111/jnc.12022

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      Mutations in CADM1 are associated with autism spectrum disorder (ASD). Cadm1 associated with multi-PDZ scaffold protein Mupp1, which interact with GABBR2. The amount of GABBR2 protein was increased in the cerebella of Cadm1-KO mice, suggesting that lack of Cadm1 does not affect transcription of GABBR2, but may stabilize the Mupp1–GABBR2 complex. Up-regulation of GABBR2 may be associated with ASD pathogenesis.

  5. OBITUARY

    1. Top of page
    2. EDITORIAL HIGHLIGHT
    3. REVIEW
    4. SHORT COMMUNICATIONS
    5. ORIGINAL ARTICLES
    6. OBITUARY
    1. You have free access to this content

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