Structural and functional rejuvenation of the aged brain by montelukast

NATURE COMMUNICATIONS | ARTICLE OPEN

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

et al.

Nature Communications

 

6,

 

Article number:

 

8466

 

doi:10.1038/ncomms9466

Received

 

09 December 2014 

Accepted

 

24 August 2015 

Published

 

27 October 2015

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Abstract

• Abstract• 
• Introduction• 
• Results• 
• Discussion• 
• Methods• 
• Additional information• 
• References•
• Acknowledgements• 
• Author information• 
• Supplementary information

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.