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.
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.
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.
The review analyzes modern concepts about the control of various mechanisms of the hippocampal neuroplasticity in adult mammals and humans by glucocorticoids. Glucocorticoid hormones ensure the coordinated functioning of key components and mechanisms of hippocampal plasticity: neurogenesis, glutamatergic neurotransmission, microglia and astrocytes, systems of neurotrophic factors, neuroinflammation, proteases, metabolic hormones, neurosteroids. Regulatory mechanisms are diverse; along with the direct action of glucocorticoids through their receptors, there are conciliated glucocorticoid-dependent effects, as well as numerous interactions between various systems and components. Despite the fact that many connections in this complex regulatory scheme have not yet been established, the study of the factors and mechanisms considered in the work forms growth points in the field of glucocorticoid-regulated processes in the brain and primarily in the hippocampus. These studies are fundamentally important for the translation into the clinic and the potential treatment/prevention of common diseases of the emotional and cognitive spheres and respective comorbid conditions.