Elevated level of small extracellular vesicules in the serum of patients with depression, epilepsy and epilepsy with depression
Small extracellular vesicles (sEVs) properties and sEVs composition are far from being well-studied for now, especially in the context of mental disorders. To elucidate the role of sEVs in disease we performed a quantitative analysis of the blood sEV in patients with focal epilepsy and patients with focal epilepsy with depression, psychogenic non-epileptic seizures with depression, pure depression, and bipolar affective disorder with the current depressive episode (cDE). Small EVs were isolated from the serum by gel filtration or PEG precipitation, and both methods showed very similar results. Subsequently, we precipitated neuronal sEVs and quantified it with several methods. Activity of lysosomal enzymes was determined in the sEVs fraction. The concentration of the blood sEVs in patients with depression, focal epilepsy, or depression with focal epilepsy was higher than in healthy controls. No difference was found between patients and controls in terms of neuronal sEVs concentration. Another finding of our work is that sEVs in the serum of patients contains various lysosomal enzymes. We suppose that the concentration of the blood sEVs in patients with depression or epilepsy is higher due to the sEVs secretion by the immune cells. Finding sEVs in the blood of patients with depression and focal epilepsy grants validity for future attempts to use sEVs as diagnostic tools for these disorders.
Structural determinants of small extracellular vesicules (exosomes) and their role in biological functions
Extracellular vesicles (EVs) are a new and actively developing area of modern experimental and theoretical biology, which attracts researchers primarily by the possibility of using EVs as diagnostic biomarkers and therapeutic agents. Currently, the greatest amount of data has been accumulated on small extracellular vesicles (sEVs) – exosomes, vesicles of endosomal origin, and ectosomes (previously known as microvesicles), which are the product of direct budding from the plasma membrane. In this review, we address the major steps in the biogenesis of exosomes and ectosomes, the major processes of intracellular membrane trafficking, and signaling involving sEVs. The role of the sEVs in the physiology and pathophysiology of the nervous system is also discussed, as well as many promising aspects of the study of sEVs biology.
Quantitative characteristics of small extracellular vesicules from the blood of patients with non-suicidal self-harm
Objective of the study – determination of quantitative characteristics of small extracellular vesicles (sEV) in the blood of patients with non-suicidal self-injury (NSSI) and comparison of the concentration and size of sEV’s in patients with major depressive disorder (MDD) with and without NSSI, as well as an assessment of the relationship between the sizes and concentrations of sEV in the sample with such parameters as the severity of situational and personal anxiety, depression and suicidal risk. The study included 28 patients (11 m./17 f.) with a current episode of major depression and at least five episodes of NSSI in the last 12 months (main group, mean age 28.3 years) and 28 patients with major depression identical in sex and age without NSSI throughout life (comparison group). Patient mental status was assessed using the MINI interview, the Beck Depression Inventory II (BDI II), and the Spielberger Anxiety Scale. Isolation of sEV from blood was carried out using polyethylene glycol (PEG) precipitation and gel filtration. The size and concentration of isolated particles were estimated using dynamic light scattering (DLS) and nanoparticle tracking analysis (ATN). The groups differed significantly in the severity of depression according to the BDI-II questionnaire, the Spielberger Situational Anxiety Scale, and the Spielberger Personality Anxiety Scale. The assessment of suicidal risk, carried out according to the corresponding module of the MINI questionnaire, revealed a significantly larger number of participants with medium and high suicidal risk in the group of patients with NSSI. The sEV fraction was isolated from the blood of the patients of the main group and the comparison group. There were no differences in the concentration and size of sEV between groups of patients with depression with and without NSSI. In our study, the dependence of the concentration and size of sEV on the severity of depression, situational and personal anxiety, and the severity of suicidal risk wasn’t revealed.
Conclusion: NSSI in individuals with major depressive disorder is associated with a more severe course of the disorder (greater severity of depression, situational and personal anxiety), as well as a higher risk of suicide. Our study did not reveal any differences in the quantitative characteristics of sEV in patients with a depressive episode with and without NSSI. Future studies should focus on investigating the structural differences and functional features of sEV in NSSI.
Number of studies devoted to investigation of neuronal exosomes increases significantly each year. Potential of exosomes as diagnostic markers of neurodegenerative diseases has been examined thoroughly and similar protocols were used to search for the markers of other psychiatric disorders. Biogenesis of exosomes in various types of cells has been studied, physiological role of exosomes has been actively investigated, and many features of their signaling cascades have been clarified. The accumulated data indicate important role of the exosome signaling in interneuronal communication. Do we have enough grounds to recognize exosomes as new non-canonical neurotransmitters in the brain? In this review we discuss this issue and present a concept on the possible role of brain exosomes as a new signaling system to the scientific community.
Transmitter signalling is the universal chemical language of any nervous system, but little is known about its early evolution. Here, we summarize data about the distribution and functions of neurotransmitter systems in basal metazoans as well as outline hypotheses of their origins. We explore the scenario that neurons arose from genetically different populations of secretory cells capable of volume chemical transmission and integration of behaviours without canonical synapses. The closest representation of this primordial organization is currently found in Placozoa, disk-like animals with the simplest known cell composition but complex behaviours. We propose that injury-related signalling was the evolutionary predecessor for integrative functions of early transmitters such as nitric oxide, ATP, protons, glutamate and small peptides. By contrast, acetylcholine, dopamine, noradrenaline, octopamine, serotonin and histamine were recruited as canonical neurotransmitters relatively later in animal evolution, only in bilaterians. Ligand-gated ion channels often preceded the establishment of novel neurotransmitter systems. Moreover, lineage-specific diversification of neurotransmitter receptors occurred in parallel within Cnidaria and several bilaterian lineages, including acoels. In summary, ancestral diversification of secretory signal molecules provides unique chemical microenvironments for behaviour-driven innovations that pave the way to complex brain functions and elementary cognition.