The astrocytic secretome increases adult hippocampal neurogenesis and spatial memory in health and disease

Abstract

INTRODUCTION: Adult hippocampal neurogenesis (AHN) plays an important role in memory and is regulated by astrocytes. Since astrocytic function deteriorates with pathological ageing and Alzheimers 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.