Treatment with the asthma drug montelukast successfully restored cognitive function and increased the creation of new brain cells in old rats in an initial study in Nature Communications. These findings provide an early indication that it may be possible to reduce the effects of ageing-associated cognitive dysfunction using montelukast, an inhibitor of the inflammatory mediator leukotriene and currently used in asthma treatment.
As human life expectancy improves, counteracting age-related cognitive impairment and dementias presents an increasing challenge. Signs of age-related cognitive decline include a slowdown in the creation of new brain cells (neurogenesis) and neuroinflammation caused by activation of the brain’s immune cells (microglia). Elevated leukotriene (an inflammatory mediator) levels have previously been reported in acute and chronic brain lesions and also in the old brain, where they may be involved in neuroinflammation by recruiting and activating microglia.
Ludwig Aigner and colleagues treat five to ten young (four-month-old) rats and a similar number of aged (20-month-old) rats with montelukast (10 mg/kg body weight) for six weeks. Learning and memory are significantly improved in aged rats, but no effect is observed in young animals. Treatment is shown to reduce neuroinflammation and increase both the creation and functional use of new brain cells.
Finally, using mouse cells genetically modified to generate less of the leukotriene receptor GRP17, the authors provide evidence that montelukast’s effects most likely occur by blocking the GRP17 receptor. These results indicate the possibility of pharmacological rejuvenation of the aged brain using montelukast.