Effect of Inducers and Inhibitors of the Keap1/Nrf2/ARE System on the Viability and Functional Activity of Model Neuronal-Like and Glial Cells.

On mouse neuroblastoma (Neuro-2a) and human glioblastoma (U-87 MG) cell lines, we studied the effect of inducers and inhibitors of redox-sensitive signaling system of the antioxidant-responsive element Keap1/Nrf2/ARE on the main processes that determine nerve cell viability and vital activity (proliferative activity, apoptosis, autophagy, and activation of the Keap1/Nrf2/ARE system). Inhibitors of the Keap1/Nrf2/ARE system stimulate apoptosis more pronouncedly than inducers, have a weaker effect on autophagy, and do not change the nuclear to cytoplasmic Nrf2 ratio. In general, the revealed effects testify in favor of the potential effectiveness of stimulating the Keap1/Nrf2/ARE system for the prevention and adjuvant therapy of neurodegenerative diseases.

Protective Effect of a New Monophenolic Antioxidant TS-13 in a Mouse Model of Parkinson's Disease.

The development of means of the prevention and treatment of age-related neurodegenerative diseases, as well as geroprotectors, among other things, is based on the inflammatory and free radical theories of aging. In this context, we studied the effect of sodium monophenol 3-(3'-tert-butyl-4'-hydroxyphenyl)propyl thiosulfonate (TS-13) on the behavioral and locomotor activity of C57BL/6 mice in modeling Parkinson's disease by MPTP neurotoxin injection. TS-13 administration significantly improved orientation and exploratory activity and emotional response of the animals in the open field test, but did not affect the increase in anxiety caused by MPTP injection. Long-term (6 months) TS-13 administration did not suppress spontaneous motor activity in BALB/c mice and slightly increased their exploratory activity.

Effect of Melatonin on the Content of CD3low and CD3hi T Cells in the Thymus of Mice with Functional Pinealectomy.

Continuous lighting for 14 days (functional pinealectomy model) leads to a decrease in the relative number of CD3low and CD3hi T lymphocytes and the CD3low/CD3hi ratio in the thymus of C57BL/6 mice. Intragastric administration of melatonin in physiological doses (1 mg/kg body weight, 14 days) against the background of functional pinealectomy restores the percentage of CD3low and CD3hi thymocytes and CD3low/CD3hi ratio to the control values. Hence, prolonged continuous illumination inhibits the differentiation and maturation of young thymocytes into mature forms, while melatonin treatment helps to compensate the effects of functional pinealectomy triggering cell proliferation in the thymus from the earliest stages of proliferation and differentiation of T cells. Thus, melatonin has immunotropic properties and can be used for correction of the consequences of functional pinealectomy.

Light-Induced Functional Pinealectomy. Effect on the Thymus of C57BL/6 Mice.

Light-induced functional pinealectomy was simulated in C57BL/6 mice by 14-day exposure to constant lighting. Immunophenotyping of CD3hi and CD3low thymocytes was performed by staining with CD3-APC antibodies followed by flow cytofluorometry. To study the cell cycle distribution of thymus cells, the content of intracellular DNA was measured by the level PI inclusion. In animals with light-induced functional pinealectomy, blood leukocyte content, the relative number of CD3low and CD3hi T cells in the thymus, and the ratio of CD3low/CD3hi thymocytes decreased. The number of G0/G1-phase thymus cells (non-dividing cells) increased and the content of S-phase cells (division phase) decreased. Continuous lighting stimulated the development of thymocyte apoptosis. The results obtained indicate that prolonged 24-h illumination inhibits differentiation and maturation of young CD3low thymocytes into mature CD3hi forms and leads to the development of T-cell apoptosis in the thymus and, as a consequence, to leukopenia.