Pharmaceutical Rejuvenation of Age-Associated Decline in Spatial Memory.

Abstract:

:Spatial memory and cognition decline during aging. Montelukast, an FDA approved drug for the treatment of asthma, can restore spatial memory in old rats to levels similar to those of young animals. Treatment improves three hallmarks of aging in the brain: reducing microglial-mediated neuroinflammation, blood-brain barrier (BBB) permeability, and increasing neurogenesis in the hippocampus although not completely to youthful levels. Other aging-associated parameters, such as reduced synaptic density, are not affected, suggesting that anti-aging therapeutics may be further optimized. Montelukast targets leukotriene receptors GPR17 and CysLTR1 and appears to invert leukotriene signaling, converting an inflammatory signal into an anti-inflammatory signal. This acts as a dominant factor to overcome the dysfunctional effects of aging reportedly mediated, in part, by blood-borne factors such as beta-2 microglobulin that inhibit neurogenesis in the dentate gyrus of the hippocampus. The key mechanism for cognitive improvement by montelukast may be restoration of BBB integrity, which would presumably decrease the amount of deleterious blood-borne factors to enter the brain. Whether or not this hypothesis is true for montelukast, drugs that restore or maintain BBB integrity may be useful in combating age-related loss of cognitive function.

journal_name

Rejuvenation Res

journal_title

Rejuvenation research

authors

Mendelsohn AR,Larrick JW

doi

10.1089/rej.2016.1903

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

521-524

issue

6

eissn

1549-1684

issn

1557-8577

journal_volume

19

pub_type

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