# Brain Synapses: Neurons, Astrocytes, and Extracellular Vesicles in Health and Diseases

## TL;DR

This paper explores how synapses, neurons, astrocytes, and extracellular vesicles interact in the brain, influencing health and diseases like Alzheimer's.

## Contribution

The paper introduces new insights into synapse assembly and function, emphasizing roles of astrocytes and extracellular vesicles in both health and disease.

## Key findings

- Synapse assembly involves pre- and post-synaptic terminals with a liquid–liquid phase governed by Ca2+ responses.
- Neurons cooperate with astrocytes and extracellular vesicles, which influence synapse function through non-canonical pathways.
- Alzheimer’s and other neurodegenerative diseases are linked to astrocyte and microglia activities and extracellular vesicle effects.

## Abstract

Synapses, abundant in the brain, are structures needed for life. Our Introduction, based on the forms of such structures published few decades ago, helped in developing recent concepts of health and diseases. Growing axons govern their growth by cell-to-cell communication, axon guidance, and synapse orientations. The assembly of synapses requires the organization and function of pre-synaptic and post-synaptic neuronal terminals with a liquid–liquid phase, governed by Ca2+ responses of thin astrocyte domains. Upon synapse stimulation, the clefts expand up to several folds while pre- and post-synaptic thickness remains unchanged. In additional responses, neurons co-operate with astrocytes and extracellular vesicles (EVs), the latter dependent on extracellular and intracellular spaces. Astrocyte and microglia cells and/or EV secretions induce neurons by various effects including traveling changes. Pre-synaptic responses are defined as canonical if based on neurotransmitter release; non-canonical if they are without release and are discharged by EVs, not neurotransmitters. Health and diseases depend on other general properties, such as those defined molecularly. Among neurodegenerative diseases, attention is specified by various properties of Alzheimer’s and other diagnoses. Critical identifications can be due to astrocyte and microglia cells or multiple effects induced by EVs. At present, the complexity of therapies, although of limited success, is developing innovative initiatives.