A recently published article by researchers from the IHNA&NPh RAS and the Moscow Research and Clinical Center for Neuropsychiatry raises new and interesting questions in the study of small extracellular vesicles (sEVs) in human blood. Previously, the team, using four different methods, had shown significant increase in the concentration of sEVs in the blood of patients with depression compared to healthy volunteers, and the followed work was intended to clarify the source of these “extra” vesicles in depression. In addition, the authors compared sEVs content in the blood of patients with a wide range of pathologies, including epilepsy, epilepsy with depression, bipolar affective disorder with a current depressive episode, and psychogenic nonepileptic seizures with depression. Small EVs were isolated from patient serum using gel filtration or polyethylene glycol (PEG) precipitation, and both methods showed very similar results. It turned out that in patients with depression, epilepsy, or epilepsy with depression, the total level of mBB in the blood is increased by up to two times compared to healthy volunteers. The authors of the work were able to go further and isolate the fraction of sEVs of neuronal origin (in the blood this is approximately every one hundred and fiftieth vesicle) in these patients, but no difference in the concentration of neuronal sEVs was found between any groups. The question of where the “extra” sEVs in the patients’ blood came from remains open. The authors suggest that the source of these sEVs are immune cells. However, the authors did discover at least one new finding that sheds light on the biogenesis of sEVs. It turned out that sEVs in the serum of both patients and healthy volunteers contain various lysosomal enzymes - and this is a hint that the contents of sEVs may reflect the state of the intracellular endolysosomal system.
On January 7, 2024, Dr. Evgenia Sitnikova's review on behavioral and neuro-cognitive comorbidities in rats with a genetic predisposition to absence epilepsy was published in the journal Biomedicines. Absence epilepsy is a non-convulsive type of epilepsy characterized by a sudden decrease in consciousness. Absence epilepsy is a disorder of the thalamo-cortical system, and it is accompanied by neurocognitive comorbidities. Absence-like seizures have been observed in many strains of albino laboratory rats, including Wistar, Sprague–Dawley, and Long Evans. Spontaneous absence-like seizures are common in adult Wistar rats, so caution should be exercised when using Wistar rats as controls. The specially bred GAERS (Genetic Absence Epilepsy Rats from Strasbourg) and WAG/Rij (Wistar Albino Rats from Rijswijk) rats are genetic models of absence epilepsy, which show behavioral and cognitive impairments similar to those of patients with absence epilepsy. In WAG/Rij rats, deficit of executive function and impairment of memory are associated with epilepsy severity. This review discusses depressive and anxiety-like behavior in GAERS and WAG/Rij rats, sex differences in concomitant cognitive impairment, and high emotionality in genetically predisposed rats. In order to better comprehend the causes of neurocognitive dysfunction in absence epilepsy, the author suggests using the concept of the "cognitive thalamus".
Keywords: genetic animal models; spontaneous absence epilepsy; drug-naive rats; fear-motivated learning; anxiety-like symptoms; depression-like symptoms; cognitive thalamus
Epilepsy, as a chronic disorder characterized by neuronal dysfunctions and by substantial disturbances of glial cells. Dr Evgenia Sitnikova, together with colleagues from Istanbul University and Acibadem Mehmet Ali Aydinlar University (Istanbul, Turkey), published a review on the role of neuroglia in epilepsy, including epileptogenesis and ictogenesis, including epileptogenesis (generation of seizure activity) and ictogenesis (generating seizure activity).
Special attention is paid to new strategies for targeted therapy of epilepsy aimed at regulating the functions of astrocytic neuroglia: (1) selective targeting of glia-related molecular mechanisms of glutamate transport; (2) modulation of tonic GABA release from astrocytes; (3) gliotransmission; (4) targeting the astrocytic Kir4.1-BDNF system; (5) astrocytic Na+/K+/ATPase activity; (6) targeting DNA hypo- or hypermethylation of candidate genes in astrocytes; (7) targeting astrocytic gap junction regulators; (8) targeting astrocytic adenosine kinase (the major adenosine-metabolizing enzyme); and (9) targeting microglia-astrocyte communication and inflammatory pathways. Details could be found in this paper [1] published in July 2023 in Frontiers in Molecular Neuroscience
1. Carcak N., Onat F., Sitnikova E. Astrocytes as a target for therapeutic strategies in epilepsy: current insights. Frontiers In Molecular Neuroscience. 2023. 16: 1183775. DOI: 10.3389/fnmol.2023.1183775
The illustration [1] published licensed under CC BY 4.0. © 2023 authors
The mother's diet during the perinatal period is the most important early environmental factor that, through epigenetic modifications, can cause changes in gene expression and, as a consequence, the phenotype of the offspring. Employees of the Institute of Higher Inspectorate and Scientific Branch of the Russian Academy of Sciences and the Institute of Molecular Genetics of the Russian Academy of Sciences were the first to show that increased DNA methylation in the early stages of ontogenesis using a maternal diet enriched with methyl supplements (MAD) suppresses the manifestation of genetic absence epilepsy and comorbid depression in the offspring of WAG/Rij rats . The beneficial phenotypic effect of maternal MOD was accompanied by increased expression of pathogenetically significant genes - the hcn1 ion channel gene and the DNA methyltransferase 1 (dnmt1) gene in the somatosensory cortex and hippocampus, as well as the hcn1, dnmt1 and tyrosine hydroxylase (th) genes in the nucleus accumbens. The therapeutic effect of maternal MOD was similar to that of ethosuximide, the first-choice drug for the treatment of absence epilepsy. It is assumed that maternal MOD can serve as a new preventive therapeutic strategy for epigenetic correction of absence epilepsy and comorbid depression in offspring.
Статья опубликована в январе 2023 года в журнале Diagnostics:
https://doi.org/10.3390/diagnostics13030398