Bidirectional Communication Between the Brain and Other Organs: The Role of Extracellular Vesicles

Abstract

A number of substances released by the brain under physiological and pathological conditions exert effects on other organs. In turn, substances produced primarily by organs such as bone marrow, adipose tissue, or the heart may have an impact on the metabolism and function and metabolism of the healthy and diseased brain. Despite a mounting amount of evidence supports such bidirectional communication between the brain and other organs, research on the function of molecular mediators carried by extracellular vesicles (EVs) is in the early stages. In addition to being able to target or reach practically any organ, EVs have the ability to cross the blood-brain barrier to transport a range of substances (lipids, peptides, proteins, and nucleic acids) to recipient cells, exerting biological effects. Here, we review the function of EVs in bidirectional communication between the brain and other organs. In a small number of cases, the role has been explicitly proven; yet, in most cases, it relies on indirect evidence from EVs in cell culture or animal models. There is a dearth of research currently available on the function of EVs-carrying mediators in the bidirectional communication between the brain and bone marrow, adipose tissue, liver, heart, lungs, and gut. Therefore, more studies are needed to determine how EVs facilitate communication between the brain and other organs.

Keywords: Bidirectional communication; Brain; Exosomes; Extracellular vesicles; Microvesicles.

Fig. 1

Schematic diagram of the process of EVs production. A To release exosomes, a cup-shaped structure composed of cell surface proteins and hydrophilic proteins forms the first invagination. This leads to the generation of early endosomes. Second, the endosomal limiting membrane invaginates inward to produce multivesicular bodies containing intraluminal vesicles. When the multivesicular bodies fuse with the plasma membrane and empty their contents, intraluminal vesicles are released and are termed exosomes once they are extracellulars. B Microvesicle formation is calcium-dependent and associated with loss of membrane asymmetry and disruption of the cellular cytoskeleton. C Apoptosis undergoes several stages, beginning with condensation of nuclear chromatin, followed by membrane blistering, and progressing to disintegration of cell contents into distinct membrane-encapsulated vesicles called apoptotic vesicles or apoptotic vesicles. EVs extracellular vesicles; MVs microvesicles

Fig. 2

Extracellular vesicle-carried substances mediate communication between the brain and other organs. BMSC bone marrow mesenchymal stem cell; TF Tissue factor, ASC apoptosis-associated speckled protein; ApoE4 Apolipoprotein E4, PDEF pigment epithelium-derived factor, LPS Lipopolysaccharide; NEP neprilysin; GABA gamma-Aminobutyric acid; exRNA extracellular RNA; MHC-II major histocompatibility complex II