Journal of Molecular Neuroscience

, Volume 53, Issue 2, pp 231–241

Increased Expression of MicroRNA-29a in ALS Mice: Functional Analysis of Its Inhibition

  • Katie Nolan
  • Mollie R. Mitchem
  • Eva M. Jimenez-Mateos
  • David C. Henshall
  • Caoimhín G. Concannon
  • Jochen H. M. Prehn
Article

DOI: 10.1007/s12031-014-0290-y

Cite this article as:
Nolan, K., Mitchem, M.R., Jimenez-Mateos, E.M. et al. J Mol Neurosci (2014) 53: 231. doi:10.1007/s12031-014-0290-y

Abstract

Endoplasmic reticulum (ER) stress has been implicated in a number of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). MicroRNAs are small ribonucleic acids which can modulate protein expression by binding to the 3′UTR of target mRNAs. We recently identified increased miR-29a expression in response to ER stress in neurons, with members of the miR-29 family implicated in cancer and neurodegeneration. We found high expression of miR-29a in the mouse brain and spinal cord by quantitative PCR analysis and increased expression of miR-29a in the spinal cord of SOD1G93A transgenic mice, a mouse model of familial ALS. In situ hybridisation experiments revealed increased miR-29a expression in the lumbar spinal cord of SOD1G93A transgenic mice from postnatal day 70 onward when compared to wild-type mice. miR-29a knockdown was achieved in the CNS in vivo after a single intracerebroventricular injection of a miR-29a-specific antagomir. While analysis of disease progression and motor function could not identify a significant alteration in ALS disease manifestations, a trend towards increased lifespan was observed in male SOD1G93A mice. These findings demonstrate that miR-29a may act as a marker for disease progression in SOD1G93A mice, and provide first proof-of-concept for a therapeutic modulation of miR-29a function in ALS.

Keywords

NeurodegenerationSOD1MicroRNAAntagomirAmyotrophic lateral sclerosis

Abbreviations

ALS

Amyotrophic lateral sclerosis

aCSF

Artificial cerebrospinal fluid

CNS

Central nervous system

DIG

Digoxigenin

ER

Endoplasmic reticulum

fALS

Familial amyotrophic lateral sclerosis

ICV

Intracerebroventricular

LNA

Locked nucleic acid

PND

Postnatal day

RT-qPCR

Quantitative real-time polymerase chain reaction

SOD1

Superoxide dismutase 1

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Katie Nolan
    • 1
  • Mollie R. Mitchem
    • 1
  • Eva M. Jimenez-Mateos
    • 1
  • David C. Henshall
    • 1
  • Caoimhín G. Concannon
    • 1
  • Jochen H. M. Prehn
    • 1
  1. 1.Centre for the Study of Neurological Disorders, Department of Physiology and Medical PhysicsRoyal College of Surgeons in IrelandDublin 2Ireland