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Authors & Affiliations
Marta Vilademunt Alcaide, Fabio Grieco, Charline Carron, Thomas Larrieu, Nicolas Toni
Abstract
The generation of new neurons in the hippocampus, known as adult hippocampal neurogenesis (AHN), is a distinctive plastic process that plays an important role in mechanisms of learning, memory, and mood regulation. Various factors intricately regulate the proliferation, survival, and differentiation of newborn neurons, shaping the neurogenic niche. Microglia and astrocytes, prominent niche components, actively regulate AHN. Microglia, acting as vigilant immune sentinels, shape AHN through direct interaction with immature neurons and the release of critical soluble factors. Similarly, astrocytes contribute by releasing molecules that enhance the proliferation of hippocampal neural stem cells and facilitate the integration of new neurons into the hippocampal network. Despite the evident impact of microglia and astrocytes on AHN, communication between these cellular orchestrators remains underexplored. This work aims to investigate whether secreted molecules from homeostatic astrocytes could counteract microglial inflammation, potentially enhancing neurogenesis and restoring cognition and memory. Using in vitro hippocampal rat primary cultures exposed to neuro-inflammatory stimuli (Lipopolysaccharide and IFNg at 100ng/ml), we found that astrocytes mitigate microglial inflammation, supported by morphology analysis, cytokine concentration, and live imaging. Further exploration using 3D culture models and a cold fix assay to study the contribution of membrane-bound proteins, revealed that both cell types secrete inflammation-buffering molecules, with membrane-bound proteins favoring astrocyte-to-microglia communication. These findings suggest that the interplay between astrocytes and microglia regulates the inflammatory reaction. This mechanism may be relevant to the regulation of adult neurogenesis in aging or inflammatory conditions like Alzheimer's disease.