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

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.

SUBMITTER: Marschallinger J

PROVIDER: S-EPMC4639806 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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

Marschallinger Julia J Schäffner Iris I Klein Barbara B Gelfert Renate R Rivera Francisco J FJ Illes Sebastian S Grassner Lukas L Janssen Maximilian M Rotheneichner Peter P Schmuckermair Claudia C Coras Roland R Boccazzi Marta M Chishty Mansoor M Lagler Florian B FB Renic Marija M Bauer Hans-Christian HC Singewald Nicolas N Blümcke Ingmar I Bogdahn Ulrich U Couillard-Despres Sebastien S Lie D Chichung DC Abbracchio Maria P MP Aigner Ludwig L

Nature communications 20151027

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) rat ...[more]

PMID: 26506265

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

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

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