Extracellular Vesicles in CNS Developmental Disorders

Abstract

The central nervous system (CNS) is the most complex structure in the body, consisting of multiple cell types with distinct morphology and function. Development of the neuronal circuit and its function rely on a continuous crosstalk between neurons and non-neural cells. It has been widely accepted that extracellular vesicles (EVs), mainly exosomes, are effective entities responsible for intercellular CNS communication. They contain membrane and cytoplasmic proteins, lipids, non-coding RNAs, microRNAs and mRNAs. Their cargo modulates gene and protein expression in recipient cells. Several lines of evidence indicate that EVs play a role in modifying signal transduction with subsequent physiological changes in neurogenesis, gliogenesis, synaptogenesis and network circuit formation and activity, as well as synaptic pruning and myelination. Several studies demonstrate that neural and non-neural EVs play an important role in physiological and pathological neurodevelopment. The present review discusses the role of EVs in various neurodevelopmental disorders and the prospects of using EVs as disease biomarkers and therapeutics.

Pregnancy-Related Extracellular Vesicles Revisited

“…Down syndrome (DS) is a chromosomal condition affecting around 1 in 800 births worldwide, caused by human chromosome 21 (Hsa21) trisomy, and it is primarily associated with intellectual disability and neurodevelopmental abnormalities occurring early in the embryonic life [ 254 , 255 ]. Being the most common chromosomal disorder, intense studies into its causes have been carried out, however, variations in clinical manifestations have been correlated with the involvement of epigenetic factors [ 256 ].…”

“…As the composition of the CNS broadly consists of several types of cells with distinct morphologies and functions, EVs may contain different loads depending on their origin. Through their cargo, they are capable of modulating signal transduction pathways, leading to subsequent changes in neurogenesis, gliogenesis, synaptogenesis, and the formation of network circuits, as well as myelination and synaptic pruning [ 254 ]. Several studies have shown that in the case of CNS dysfunctions, including DS, the composition of EVs varies depending upon biogenetic pathways and parental cells [ 259 ].…”

“…Several studies have shown that in the case of CNS dysfunctions, including DS, the composition of EVs varies depending upon biogenetic pathways and parental cells [ 259 ]. In addition to the endosomal sorting complexes required for transport (ESCRT), apoptosis-linked gene 2-interacting protein X (Alix), and tumor susceptibility gene 101 (TSG101) proteins, currently considered standard markers of exosomes, regardless of parental cells, several types of membrane, cytosolic, and cytoskeletal proteins have commonly been found in exosomes isolated from neuronal cells [ 254 , 260 , 261 ]. In the interest of facilitating non-invasive prenatal testing, Erturk et al have analyzed miRNAs originating in trophoblast-derived EVs from pregnant women with fetuses suffering from DS, and found that miR-99a and miR-3156 levels were significantly higher compared to women carrying healthy fetuses [ 262 ].…”

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

“…Endosomal sorting complex required for transport (ESCRT) proteins, Alix, and TSG101 are standard markers of exosomes that derive from any parent cell since they are necessary for the biogenesis of multivesicular bodies. Integrins and tetraspanins, such as CD63, are common membrane proteins found in exosomes along with cytosolic proteins, such as Hsp70 and Hsp90 [83].…”

Cerebrospinal Fluid of Patients With Alzheimer’s Disease Contains Increased Percentages of Synaptophysin-Bearing Microvesicles

“…The properties and functions of these MVs are slowly being revealed. Their functions include neurodevelopment ( Gomes et al, 2020 ), cell-to-cell communication, and even synaptic transmission ( Krämer-Albers and Hill, 2016 ). Along with exosomes, MVs are discussed as vehicles for the intercellular spread of pathologically hyperphosphorylated tau ( Sharma et al, 2013 ; Coleman and Hill, 2015 ; Quek and Hill, 2017 ; Ruan et al, 2021 ).…”