Get access

Increased LINGO1 in the cerebellum of essential tremor patients

Authors

  • Charlotte Delay PhD,

    1. Faculty of Pharmacy, Université Laval, Québec City, Québec, Canada
    2. Centre de Recherche du Centre Hospitalier Universitaire de Québec, Neurosciences Axis, Québec City, Québec, Canada
    Search for more papers by this author
    • The first two authors contributed equally to this work.

  • Cyntia Tremblay MSc,

    1. Faculty of Pharmacy, Université Laval, Québec City, Québec, Canada
    2. Centre de Recherche du Centre Hospitalier Universitaire de Québec, Neurosciences Axis, Québec City, Québec, Canada
    Search for more papers by this author
    • The first two authors contributed equally to this work.

  • Elodie Brochu MSc,

    1. Faculty of Pharmacy, Université Laval, Québec City, Québec, Canada
    2. Centre de Recherche du Centre Hospitalier Universitaire de Québec, Neurosciences Axis, Québec City, Québec, Canada
    Search for more papers by this author
  • Sarah Paris-Robidas BSc,

    1. Faculty of Pharmacy, Université Laval, Québec City, Québec, Canada
    2. Centre de Recherche du Centre Hospitalier Universitaire de Québec, Neurosciences Axis, Québec City, Québec, Canada
    Search for more papers by this author
  • Vincent Emond PhD,

    1. Faculty of Pharmacy, Université Laval, Québec City, Québec, Canada
    2. Centre de Recherche du Centre Hospitalier Universitaire de Québec, Neurosciences Axis, Québec City, Québec, Canada
    Search for more papers by this author
  • Ali H. Rajput MD, FRCPC,

    1. Division of Neurology, Royal University Hospital, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
    Search for more papers by this author
  • Alex Rajput MD, FRCPC,

    1. Division of Neurology, Royal University Hospital, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
    Search for more papers by this author
  • Frédéric Calon BPharm, PhD

    Corresponding author
    1. Faculty of Pharmacy, Université Laval, Québec City, Québec, Canada
    2. Centre de Recherche du Centre Hospitalier Universitaire de Québec, Neurosciences Axis, Québec City, Québec, Canada
    • Correspondence to: Dr. Frédéric Calon, Centre de Recherche du CHU de Québec, Pavillon CHUL, Room T2-05, 2705 Laurier Blvd., Quebec, QC, Canada, G1V 4G2; frederic.calon@crchul.ulaval.ca

    Search for more papers by this author

  • Funding agencies: Dr. Calon was supported by an International Essential Tremor Foundation grant, Canada Foundation for Innovation grant 10307, and a Fonds de la Recherche en Santé du Québec (FRSQ) salary award.

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

ABSTRACT

Essential tremor (ET) is the most prevalent adult-onset movement disorder. Despite its health burden, no clear pathognomonic sign has been identified to date because of the rarity of clinicopathological studies. Moreover, treatment options are still scarce and have not significantly changed in the last 30 years, underscoring the urgent need to develop new treatment avenues. In the recent years, leucine-rich repeat (LRR) and immunoglobulin (Ig) domain-containing Nogo receptor-interacting proteins 1 and 2 (LINGO1 and LINGO2, respectively) have been increasingly regarded as possible ET modulators due to emerging genetic association studies linking LINGO with ET. We have investigated LINGO protein and messenger RNA (mRNA) expression in the cerebellum of patients with ET, patients with Parkinson's disease (PD), and a control group using Western immunoblotting and in situ hybridization. Protein levels of LINGO1, but not LINGO2, were significantly increased in the cerebellar cortex of ET patients compared with controls, particularly in individuals with longer disease duration. Compared with controls, LINGO1 protein levels were increased in the cerebellar white matter of PD and ET patients but, for the latter, only when disease duration exceeded 20 years. However, no alteration in LINGO1 mRNA was observed between groups in either the cerebellar cortex or the white matter. We observed alterations in LINGO expression in diseased brain that seemed to progress along with the disease, being initiated in the cerebellar cortex before reaching the white matter. Because LINGO up-regulation has been identified as a potential pathological response to ongoing neurodegenerative processes, the present data suggest that LINGO1 is a potential drug target for ET. © 2014 International Parkinson and Movement Disorder Society

Get access to the full text of this article

Ancillary