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

Nature Communications, 2015 · DOI: 10.1038/ncomms9466 · Published: October 27, 2015

Simple Explanation

This study investigates whether montelukast, an anti-asthmatic drug, can improve cognitive function in aged rats. The researchers found that montelukast reduces neuroinflammation, elevates hippocampal neurogenesis, and improves learning and memory in old animals. The effect is mediated through inhibition of the GPR17 receptor, suggesting a potential target for treating dementias.

Study Duration

6 weeks

Participants

Young (4 months) and old (20 months) rats

Evidence Level

Level 2: Experimental Study

Key Findings

1
Montelukast treatment significantly improved task learning in old rats to a level comparable to young ones.
2
Montelukast treatment fully restored these memory impairments in the old rats, while it did not affect memory in the young animals.
3
Montelukast treatment reduced the soma size of microglia in old rats, suggesting a less reactive phenotype.

Research Summary

The present work demonstrates that the anti-asthmatic drug and leukotriene receptor antagonist montelukast restores learning and memory function in old rats. Montelukast treatment reduced age-associated neuroinflammation, in particular microglia activation. Here, we are demonstrating for the first time that montelukast promotes hippocampal neurogenesis, in particular progenitor cell proliferation, which results in an increased number of newly generated neurons.

Practical Implications

Potential Treatment for Dementia

Inhibition of leukotriene receptor signaling might represent a safe and druggable target to restore cognitive functions in old individuals and pave the way for future clinical translation for the treatment of dementias.

Anti-inflammatory Effects

Montelukast reduces age-associated neuroinflammation, particularly microglia activation, suggesting a less reactive phenotype in the brain.

Neurogenesis Enhancement

Montelukast promotes hippocampal neurogenesis, which is crucial for learning and memory, especially in situations where neurogenesis is compromised due to aging.

Study Limitations

1
The precise function of CD68 is not well understood
2
The exact interrelations between specific patterns of neuroinflammation and neurogenesis
3
The exact downstream signalling components that mediate the beneﬁcial effects of montelukast in the old rats are not fully deciphered at present

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