Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug

Julia Marschallinger, Iris Schäffner, Barbara Klein, Renate Gelfert, Francisco J. Rivera, Sebastian Illes, Lukas Grassner, Maximilian Janssen, Peter Rotheneichner, Claudia Schmuckermair, Roland Coras, Marta Boccazzi, Mansoor Chishty, Florian B. Lagler, Marija Renic, Hans-Christian Bauer, Nicolas Singewald, Ingmar Blümcke, Ulrich Bogdahn, Sebastien Couillard-Despres, D. Chichung Lie, Maria P. Abbracchio and Ludwig Aigner ()
Additional contact information
Julia Marschallinger: Institute of Molecular Regenerative Medicine, Paracelsus Medical University
Iris Schäffner: Institute of Biochemistry, Emil Fischer Center, Friedrich-Alexander-University Erlangen-Nürnberg
Barbara Klein: Institute of Molecular Regenerative Medicine, Paracelsus Medical University
Renate Gelfert: Institute of Molecular Regenerative Medicine, Paracelsus Medical University
Francisco J. Rivera: Institute of Molecular Regenerative Medicine, Paracelsus Medical University
Sebastian Illes: Institute of Molecular Regenerative Medicine, Paracelsus Medical University
Lukas Grassner: Institute of Molecular Regenerative Medicine, Paracelsus Medical University
Maximilian Janssen: Institute of Molecular Regenerative Medicine, Paracelsus Medical University
Peter Rotheneichner: Institute of Molecular Regenerative Medicine, Paracelsus Medical University
Claudia Schmuckermair: Institute of Pharmacy and CMBI, Leopold-Franzens-University of Innsbruck
Roland Coras: University Hospital Erlangen
Marta Boccazzi: University of Milan
Mansoor Chishty: Pharmidex
Florian B. Lagler: Institute for Inborn Errors of Metabolism, Paracelsus Medical University
Marija Renic: Croatian Institute for Brain Research, University of Zagreb School of Medicine
Hans-Christian Bauer: Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University
Nicolas Singewald: Institute of Pharmacy and CMBI, Leopold-Franzens-University of Innsbruck
Ingmar Blümcke: University Hospital Erlangen
Ulrich Bogdahn: University Hospital Regensburg
Sebastien Couillard-Despres: Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University
D. Chichung Lie: Institute of Biochemistry, Emil Fischer Center, Friedrich-Alexander-University Erlangen-Nürnberg
Maria P. Abbracchio: University of Milan
Ludwig Aigner: Institute of Molecular Regenerative Medicine, Paracelsus Medical University

Nature Communications, 2015, vol. 6, issue 1, 1-16

Abstract: Abstract As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood–brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias.

Date: 2015
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DOI: 10.1038/ncomms9466

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