The Dichotomous Role of Extracellular Vesicles in the Central Nervous System

Abstract

Summary Extracellular vesicles (EVs) are important mediators of intercellular communication. Interest in the role of central nervous system (CNS)-derived EVs has been increasing; however, some skepticism of their importance has persisted because many aspects of their biology remain elusive. This ambiguity is largely due to technical barriers that hamper our ability to achieve a comprehensive understanding of their molecular components and mechanisms responsible for their transmission and uptake. However, accumulating evidence supports the notion that EVs play important roles in basic physiological processes within the CNS during neurodevelopment and synaptic plasticity. Interestingly, EVs also act to spread toxic polypeptides in neurodegenerative diseases. Developing a more profound understanding of the role that EVs play in the CNS could lead to the identification of biomarkers and potential vehicles for drug delivery. Here we highlight our current understanding of CNS EVs and summarize our current understanding of their complex role in the CNS.

Evidence for Effects of Extracellular Vesicles on Physical, Inflammatory, Transcriptome and Reward Behaviour Status in Mice

“…Inter-estingly, a more marked effect was observed between LPS-EV-aCSF mice compared with SAL-EV-aCSF mice than with aCSF mice in terms of the number of differentially expressed genes: This was mainly due to upregulation of transcript expression in LPS-EV-aCSF mice compared with aCSF mice and downregulation of expression of the same transcripts in SAL-EV-aCSF mice compared with aCSF mice. Opposite effects of immune-challenged versus naïve EVs from the same cellular source have been reported [22,29,59], suggesting that these might be mediated by different/opposite transcriptional regulation. The 10 genes that were upregulated in LPS-EV-aCSF versus both SAL-EV-aCSF and aCSF mice were significantly enriched for immune-inflammatory pathways, including LPS-mediated signalling pathway, suggesting EV involvement in such processes.…”

Toxic and Teratogenic Effects of Prenatal Alcohol Exposure on Fetal Development, Adolescence, and Adulthood

“…It has been shown that environmental stressors alter the secretion and composition of EVs, therefore controlling their function. In neurogenesis, EVs coordinate behavior between various cell types of the developing brain [88]. During the neonatal period of mice, in vivo neural stem cell (NSC)-derived EVs cause a decrease in microglial complexity and an increase in cytokine production due to preferential signaling of microglia [89].…”

Extracellular Vesicles in Regeneration and Rehabilitation Recovery after Stroke

“…EVs also play an active role in intercellular communication by carrying soluble mediators such as cytokines [ 26 ] and being vectors of genetic information able to modify the range of genes in the recipient cells [ 28 , 29 ]. Thanks to their cell-to-cell communication role, in the central nervous system EVs were demonstrated to maintain physiological homeostasis; mediate cellular proliferation, differentiation, senescence, and synaptic activity; allow clearance of unwanted materials and cellular waste; and likely improve neuroprotection and regeneration in brain diseases [ 23 , 30 , 31 ].…”