Epilepsy is a severe neurological disease characterized by spontaneous recurrent seizures (SRS). A complex pathophysiological process referred to as epileptogenesis transforms a normal brain into an epileptic one. Prevention of epileptogenesis is a subject of intensive research. Currently, there are no clinically approved drugs that can act as preventive medication. Our previous studies have revealed highly promising antiepileptogenic properties of a compound–myo-inositol (MI) and the present research broadens previous results and demonstrates the long-term disease-modifying effect of this drug, as well as the amelioration of cognitive comorbidities. For the first time, we show that long-term treatment with MI: (i) decreases the frequency and duration of electrographic SRS in the hippocampus; (ii) has an ameliorating effect on spatial learning and memory deficit associated with epileptogenesis, and (iii) attenuates cell loss in the hippocampus. MI treatment also alters the expression of the glial fibrillary acidic protein, LRRC8A subunit of volume-regulated anion channels, and protein tyrosine phosphatase receptor type R, all expected to counteract the epileptogenesis. All these effects are still present even 4 weeks after MI treatment ceased. This suggests that MI may exert multiple actions on various epileptogenesis-associated changes in the brain and, therefore, could be considered as a candidate target for prevention of epileptogenesis.

Identification of compounds preventing or modifying the biochemical changes that underlie the epileptogenesis process and understanding the mechanism of their action are of great importance. We have previously shown that myoinositol (MI) daily treatment for 28 days prevents certain biochemical changes that are triggered by kainic acid (KA) induced status epilepticus (SE). However in these studies we have not detected any effects of MI on the first day after SE. In the present study we broadened our research and focused on other molecular and morphological changes at the early stages of SE induced by KA and effects of MI treatment on these changes. The increase in the amount of voltage-dependent anionic channel-1 (VDAC-1), cofilin, and caspase-3 activity was observed in the hippocampus of KA treated rats. Administration of MI 4 hours later after KA treatment abolishes these changes, whereas diazepam treatment by the same time schedule has no significant influence. The number of neuronal cells in CA1 and CA3 subfields of hippocampus is decreased after KA induced SE and MI posttreatment significantly attenuates this reduction. No significant changes are observed in the neocortex. Obtained results indicate that MI posttreatment after KA induced SE could successfully target the biochemical processes involved in apoptosis, reduces cell loss, and can be successfully used in the future for translational research.

Epilepsy is one of the most devastating neurological diseases and despite significant efforts there is no cure available. Occurrence of spontaneous seizures in epilepsy is preceded by numerous functional and structural pathophysiological reorganizations in the brain—a process called epileptogenesis. Treatment strategies targeting this process may be efficient for preventing spontaneous recurrent seizures (SRS) in epilepsy, or for modification of disease progression. We have previously shown that (i) myoinositol (MI) pretreatment significantly decreases severity of acute seizures (status epilepticus: SE) induced by kainic acid (KA) in experimental animals and (ii) that daily post-SE administration of MI for 4 weeks prevents certain biochemical changes triggered by SE. However it was not established whether such MI treatment also exerts long-term effects on the frequency of SRS. In the present study we have shown that, in KA-induced post-SE epilepsy model in rats, MI treatment for 28 days reduces frequency and duration of behavioural SRS not only during the treatment, but also after its termination for the following 4 weeks. Moreover, MI has significant effects on molecular changes in the hippocampus, including mi-RNA expression spectrum, as well as mRNA levels of sodium-MI transporter and LRRC8A subunit of the volume regulated anionic channel. Taken together, these data suggest that molecular changes induced by MI treatment may counteract epileptogenesis. Thus, here we provide data indicating antiepileptogenic properties of MI, which further supports the idea of developing new antiepileptogenic and disease modifying drug that targets MI system.

Rett syndrome (RTT) is a genetic neurodevelopmental disorder with mutations in the X-chromosomal MECP2 (methyl-CpG-binding protein 2) gene. Most patients are young girls. For 7–18 months after birth, they hardly present any symptoms; later they develop mental problems, a lack of communication, irregular sleep and breathing, motor dysfunction, hand stereotypies, and seizures. The complex pathology involves mitochondrial structure and function. Mecp2^−/y hippocampal astrocytes show increased mitochondrial contents. Neurons and glia suffer from oxidative stress, a lack of ATP, and increased hypoxia vulnerability. This spectrum of changes demands comprehensive molecular studies of mitochondria to further define their pathogenic role in RTT. Therefore, we applied a comparative proteomic approach for the first time to study the entity of mitochondrial proteins in a mouse model of RTT. In the neocortex and hippocampus of symptomatic male mice, two-dimensional gel electrophoresis and subsequent mass-spectrometry identified various differentially expressed mitochondrial proteins, including components of respiratory chain complexes I and III and the ATP-synthase FoF1 complex. The NADH-ubiquinone oxidoreductase 75 kDa subunit, NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, NADH dehydrogenase [ubiquinone] flavoprotein 2, cytochrome b-c1 complex subunit 1, and ATP synthase subunit d are upregulated either in the hippocampus alone or both the hippocampus and neocortex of Mecp2^−/y mice. Furthermore, the regulatory mitochondrial proteins mitofusin-1, HSP60, and 14-3-3 protein theta are decreased in the Mecp2^−/y neocortex. The expressional changes identified provide further details of the altered mitochondrial function and morphology in RTT. They emphasize brain-region-specific alterations of the mitochondrial proteome and support the notion of a metabolic component of this devastating disorder.

The recent emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an ongoing global COVID-19 pandemic and public health crisis. Detailed study of human immune response to SARS-COVIS-2 infection is the important topic for a successful treatment of this disease. Our study was aimed to characterize immune response on the level of antibody profiling in convalescent plasma of patients in Georgia. Antibodies against the following SARS-COV-2 proteins were studied: nucleocapsid and various regions of Spike (S) protein: S1, S2 and Receptor binding domain (RBD). Convalescent plasma of patients 6-8 weeks after initial confirmation of SARS-COV-2 infection were tested. Nearly 80% out of 154 patients studied showed presence of antibodies against nucleocapsid protein. The antibody response to three fragments of S protein was significantly less and varied in the range of 20-30%. Significantly more females as compared to males were producing antibodies against S1 fragment, whereas the difference between genders by the antibodies against nucleocapsid protein and RBD was statistically significant only by one-tailed Fisher exact test. There were no differences between the males and females by antibodies against S2 fragment. Thus, immune response against some viral antigens are stronger in females and we suggest that it could be one of the factors of less female fatality after SARS-COVID-2 infection.