The emerging role of exosomes in mental disorders

Abstract

Exosomes are a class of extracellular vesicles of endocytic origin, which are released by cells and are accessible in biofluids, such as saliva, urine, and plasma. These vesicles are enriched with small RNA, and they play a role in many physiological processes. In the brain, they are involved in processes including synaptic plasticity, neuronal stress response, cell-to-cell communication and neurogenesis. While exosomes have been implicated previously in cancer and neurodegenerative diseases, research regarding their role in mental disorders remains scarce. Given their functional significance in the brain, investigation in this field is warranted. Additionally, because exosomes can cross the blood-brain barrier, they may serve as accessible biomarkers of neural dysfunction. Studying exosomes may provide information towards diagnosis and therapeutic intervention, and specifically those derived from the brain may provide a mechanistic view of the disease phenotype. This review will discuss the roles of exosomes in the brain, and relate novel findings to current insights into mental disorders.

Fig. 1. Extracellular vesicle (EV) biogenesis and cell-to-cell communication.

Apoptotic bodies, the largest of the EVs, “bleb” off the cell membrane and contain material from cells undergoing apoptosis to signal to macrophages. Microvesicles bud off the plasma membrane and contain cargo that can facilitate signaling to recipient cells. Exosomes are the smallest of the vesicles, and are first made as a population of heterogeneous intraluminal vesicles in the multivesicular body (MVB). The MVB has two fates, either fusing with the lysosome, or fusing with the plasma membrane where they are released as exosomes. Exosomes can be taken up by other cells either by endocytosis, micropinocytosis, or phagocytosis where its contents can effectively influence cellular processes. Contents can be involved in transcriptional regulation, or mRNA cargo can be transcribed in recipient cells

Fig. 2. The role of exosomes in the brain.

Exosome signalling is involved in many physiological brain processes. Changes in many of these processes have been previously associated in mental disorders. For example, activated monocytes release exosomes that can influence BBB permeability. A leaky BBB is associated with neuroinflammation, and has been previously implicated in schizophrenia, bipolar disorder, and major depressive disorder. Additionally, exosomes carry markers from parent cells that may help them be distinguishable in biofluids