The astrocytic secretome increases adult hippocampal neurogenesis and spatial memory in health and disease
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INTRODUCTION
Adult hippocampal neurogenesis (AHN) plays an important role in memory and is regulated by astrocytes. Since astrocytic function deteriorates with pathological ageing and Alzheimer’s disease (AD), we hypothesize that the astrocytic secretome may rescue AHN and cognition.
METHODS
We tested the effect of astrocyte-conditioned solution (ACS) on AHN and memory performances in young and aged mice and in two models of AD.
RESULTS
ACS increased AHN and improved performance in the object location test in young and aged wild-type mice. In THY-Tau22 mice, a model of tau pathology, ACS restored AHN and cognitive performance. In APP/PS1 mice, a model of amyloid pathology, ACS reduced gliogenesis, and rescued deficits in AHN and spatial memory. In addition, ACS attenuated circulating pro-inflammatory cytokines and the reaction of plaque-associated microglia.
DISCUSSION
The astrocytic secretome is a promising, niche-targeted strategy to enhance hippocampal plasticity and memory across ageing and AD.
