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.
Highlights
Mature cortical and hippocampal neurons secrete exosomes [29]. These studies highlight the role of Extracellular vesicles (EVs) in regulating synaptic activity during development, their role in neuronal communication mediated by glutamatergic synaptic activity, 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors [29]
This study showed that the loss of methyl-CpG-binding protein 2 (MeCP2) function (MeCP2LOF) was associated with a dramatic change in the protein content of exosomes and the signaling bioactivity of the exosomes
In a more recent work using a Ts2 mouse model, it was observed that the higher levels of exosomes released in Down syndrome (DS) models was associated with more multivesicular bodies (MVBs) per neuron and an increased number of intraluminal vesicles (ILVs) per MVB when compared with controls
Summary
Cell-to-cell communication is a fundamental process in coordinating the functions and interactions between the diverse neural cell populations in the central nervous system (CNS) and is mainly organized through secretion of molecules in the intercellular space [1]. A subset of EVs, the exosomes, originate from the inward budding of endosomal membranes, giving rise to the formation of multivesicular bodies (MVBs). MVBs typically depict a diameter between 250–1000 nm and contain intraluminal vesicles (ILVs), which are released into the extracellular space as exosomes after the fusion of MVBs with the plasma membrane [3]. Isolation by differential ultracentrifugation is widely considered the gold standard method [8,9,10]. It should be noted, that physical and molecular overlap between the EV subsets has precluded the definition of specific EV subtype marker proteins to date [11]
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