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Neuroscience

  • <em>C9ORF72</em>-derived poly-GA DPRs undergo endocytic uptake in iAstrocytes and spread to motor neurons
    Open Access
    C9ORF72-derived poly-GA DPRs undergo endocytic uptake in iAstrocytes and spread to motor neurons

    Paolo M Marchi, Lara Marrone, Laurent Brasseur, Audrey Coens, Christopher P Webster, Luc Bousset, Marco Destro, Emma F Smith, Christa G Walther, Victor Alfred, Raffaele Marroccella, Emily J Graves, Darren Robinson, Allan C Shaw, Lai Mei Wan, Andrew J Grierson, Stephen J Ebbens, Kurt J De Vos, Guillaume M Hautbergue, Laura Ferraiuolo, Ronald Melki, Mimoun Azzouz

    Paolo M Marchi ... Mimoun Azzouz

    Published 13 May 2022

    Extracellularly delivered poly-GAs are internalised into astrocytes via an endocytosis-dependent pathway and then spread to motor neurons, implying non-cell autonomous mechanisms in C9ORF72-ALS/FTD.

  • Analyzing efficacy, stability, and safety of AAV-mediated optogenetic hearing restoration in mice
    Open Access
    Analyzing efficacy, stability, and safety of AAV-mediated optogenetic hearing restoration in mice

    Burak Bali, Eva Gruber-Dujardin, Kathrin Kusch, Vladan Rankovic, Tobias Moser

    Burak Bali ... Tobias Moser

    Published 5 May 2022

    This longitudinal study revealed stable expression of the fast-gating channelrhodopsin f-Chrimson in cochlear neurons of mice over at least 2 yr upon a single postnatal AAV dosing of the cochlea.

  • SMN-deficient cells exhibit increased ribosomal DNA damage
    Open Access
    SMN-deficient cells exhibit increased ribosomal DNA damage

    Evangelia Karyka, Nelly Berrueta Ramirez, Christopher P Webster, Paolo M Marchi, Emily J Graves, Vinay K Godena, Lara Marrone, Anushka Bhargava, Swagat Ray, Ke Ning, Hannah Crane, Guillaume M Hautbergue, Sherif F El-Khamisy, Mimoun Azzouz

    Evangelia Karyka ... Mimoun Azzouz

    Published 19 April 2022

    SMN deficiency leads to elevated ribosomal DNA damage that results in impaired ribosomal RNA synthesis and translation and is accompanied by a motor neuron-specific down-regulation of DDX21 protein.

  • Septins tune lipid kinase activity and PI(4,5)P<sub>2</sub> turnover during G-protein–coupled PLC signalling in vivo
    Open Access
    Septins tune lipid kinase activity and PI(4,5)P2 turnover during G-protein–coupled PLC signalling in vivo

    Aastha Kumari, Avishek Ghosh, Sourav Kolay, Padinjat Raghu

    Aastha Kumari ... Padinjat Raghu

    Published 11 March 2022

    In Drosophila photoreceptors, PI(4,5)P2 synthesis during PLC signalling is regulated by PIP5K and septins.

  • Transcellular blood–brain barrier disruption in malaria-induced reversible brain edema
    Open Access
    Transcellular blood–brain barrier disruption in malaria-induced reversible brain edema

    Jessica Jin, Mame Aida Ba, Chi Ho Wai, Sanjib Mohanty, Praveen K Sahu, Rajyabardhan Pattnaik, Lukas Pirpamer, Manuel Fischer, Sabine Heiland, Michael Lanzer, Friedrich Frischknecht, Ann-Kristin Mueller, Johannes Pfeil, Megharay Majhi, Marek Cyrklaff, Samuel C Wassmer, Martin Bendszus, Angelika Hoffmann

    Jessica Jin ... Angelika Hoffmann

    Published 8 March 2022

    We present how reversible edema can reliably be induced in experimental cerebral malaria and show that it is associated with transcellular blood–brain barrier disruption and delayed microhemorrhages.

  • Testing of the therapeutic efficacy and safety of AMPA receptor RNA aptamers in an ALS mouse model
    Open Access
    Testing of the therapeutic efficacy and safety of AMPA receptor RNA aptamers in an ALS mouse model

    Megumi Akamatsu, Takenari Yamashita, Sayaka Teramoto, Zhen Huang, Janet Lynch, Tatsushi Toda, Li Niu, Shin Kwak

    Megumi Akamatsu ... Shin Kwak

    Published 12 January 2022

    RNA aptamers designed to block AMPA receptors effectively reduce progression of motor dysfunction, improve TDP-43 pathology, and prevent death of motor neurons in AR2 mice, a mouse model of sporadic ALS, without adverse effects.

  • β-arrestin1 promotes tauopathy by transducing GPCR signaling, disrupting microtubules and autophagy
    Open Access
    β-arrestin1 promotes tauopathy by transducing GPCR signaling, disrupting microtubules and autophagy

    Jung-AA Woo, Yan Yan, Teresa R Kee, Sara Cazzaro, Kyle C McGill Percy, Xinming Wang, Tian Liu, Stephen B Liggett, David E Kang

    Jung-AA Woo ... David E Kang

    Published 3 December 2021

    GPCRs regulator, β-arrestin1, is increased in FTLD-tau patients, is required for β2-adrenergic receptor and metabotropic glutamate receptor 2-induced tau phosphorylation, promotes tau aggregation by impairing autophagy, and destabilizes microtubule dynamics, whereas genetic reduction in β-arrestin1 mitigates tauopathy and cognitive impairments.

  • MANF supports the inner hair cell synapse and the outer hair cell stereocilia bundle in the cochlea
    Open Access
    MANF supports the inner hair cell synapse and the outer hair cell stereocilia bundle in the cochlea

    Kuu Ikäheimo, Anni Herranen, Vilma Iivanainen, Tuuli Lankinen, Antti A Aarnisalo, Ville Sivonen, Kashyap A Patel, Korcan Demir, Mart Saarma, Maria Lindahl, Ulla Pirvola

    Kuu Ikäheimo ... Ulla Pirvola

    Published 23 November 2021

    The authors show in the mouse how the auditory hair cell structural maintenance is perturbed by the inactivation of Manf and the concomitant ER stress, causing early-onset, progressive hearing loss.

  • TGFβ-induced expression of long noncoding lincRNA Platr18 controls breast cancer axonogenesis
    Open Access
    TGFβ-induced expression of long noncoding lincRNA Platr18 controls breast cancer axonogenesis

    Simon Grelet, Cécile Fréreux, Clémence Obellianne, Ken Noguchi, Breege V Howley, Annamarie C Dalton, Philip H Howe

    Simon Grelet ... Philip H Howe

    Published 22 November 2021

    Tumor axonogenesis is an emerging hallmark of cancer and TGF-beta is a well-known cytokine involved in the control of cancer progression. In this study we identify a novel function for the TGF-beta signaling in cancer aggressivity by promoting cancer axonogenesis.

  • A brain-specific <em>pgc1</em>α fusion transcript affects gene expression and behavioural outcomes in mice
    Open Access
    A brain-specific pgc1α fusion transcript affects gene expression and behavioural outcomes in mice

    Oswaldo A Lozoya, Fuhua Xu, Dagoberto Grenet, Tianyuan Wang, Korey D Stevanovic, Jesse D Cushman, Thomas B Hagler, Artiom Gruzdev, Patricia Jensen, Bairon Hernandez, Gonzalo Riadi, Sheryl S Moy, Janine H Santos, Richard P Woychik

    Oswaldo A Lozoya ... Richard P Woychik

    Published 14 October 2021

    This study shows that loss of a brain-specific fusion isoform of PGC1a leads to up-regulation of genes and motor impairments in mice, suggesting functional differences between PGC1 isoforms in the brain.

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