# Bidirectional Communication Between Astrocytes and Neurons via Extracellular Vesicles: A Multi‐Omics Approach

## TL;DR

This study shows how astrocytes and neurons in the mouse brain communicate using tiny vesicles, changing each other's gene activity and protein content.

## Contribution

The paper introduces a multi-omics approach to reveal bidirectional communication between astrocytes and neurons via extracellular vesicles.

## Key findings

- EVs from both astrocytes and neurons caused specific changes in gene activity related to cell function and energy.
- Proteomic analysis showed that EV cargo changes dynamically based on cell interactions in co-cultures.
- The study highlights how EVs mediate communication by altering gene expression in target cells.

## Abstract

Cells modulate their physiology through multiple mechanisms—cell–cell contacts and autocrine/paracrine signaling, including via extracellular vesicles (EVs). In this study, we exposed mouse hippocampal astrocyte and neuron monocultures to EVs from the opposing cell type and subsequently performed RNA sequencing to examine transcriptomic changes. Mass spectrometry was used to analyze the proteomes of EVs from astrocyte and neuron monocultures, as well as from astrocyte‐neuron co‐cultures, to investigate the molecular basis of EVs‐induced transcriptomic alterations and to determine the extent to which cells adjust EV cargo in response to feedback signals. EVs secreted by both cell types induced cell‐specific transcriptomic changes in target cells, related to migration, proliferation, differentiation, and energy production. Unique changes in the proteome of EVs from astrocytic‐neuronal co‐cultures highlighted the dynamic regulation of signaling molecule secretion via cell interactions.

Schematic diagram illustrating the communication between mouse hippocampal astrocytes and neurons through extracellular vesicles (EVs). The illustration highlights unique proteins secreted by each cell type within EVs, with vesicle size proportional to the concentration of secreted proteins. Additionally, within the cells, selected genes that are upregulated in response to EVs from the opposite cell type are marked with red arrows, while those downregulated are marked with blue arrows. AEVs, astrocytic extracellular vesicles; NEVs, neuronal extracellular vesicles.