Biology subjects

Casse, F.

Publications and source records attributed to Casse, F..

2 recordsLinked to original sources

bioRxiv2026

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

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.

neuroscience↗

bioRxiv2024

Astrocyte-derived PEA116 increases adult hippocampal neurogenesis and confers stress resilience

In the dentate gyrus of the hippocampus, the neurogenic niche regulates several steps of adult neurogenesis, from the proliferation to the integration of newly formed neurons in the hippocampal network. However, the role of astrocytes in the regulation of adult neural stem cell (aNSC) proliferation is still little described. Here, we found that blocking vesicular release from astrocytes decreased cell proliferation in the dentate gyrus, resulting in impaired adult neurogenesis. Inversely, astrocyte-conditioned medium increased cell proliferation in a vesicular release-dependent manner. We identified PEA116 as a peptide released by astrocytes, that is derived from the c-terminal portion of the PEA15 protein and increased cell proliferation. PEA116 increased ERK2 phosphorylation, decreased the expression of genes involved in aNSC quiescence, resulting in aNSC quiescence exit. The ensuing increase in hippocampal neurogenesis improved resilience to chronic stress. These findings highlight a novel peptide produced by astrocytes that regulates the early steps of adult neurogenesis, with an implication for mood disorders.

neuroscience↗