Том 10, № 2 (2016)

We studied groups of internuclear interneurons (IN) that are located between the magnocellular and parvocellular reticular nuclei (IN1), reticular parvocellular nucleus, the nucleus of the solitary tract (IN2), and around the reticular lateral nucleus (IN3) that expreßs the neuronal NO-synthase, cystathionine ß-synthase, or heme oxygenase-2 in the medulla oblongata of Wistar rats using histochemical and immunohistochemical methods. We found local differences in the organization of INs. These differences were evident between IN1 cells, a cell group that consists of a relatively large number of large neurons, including giant cells, and IN2–IN3 cells. In interneurons of the latter two IN groups, we found significantly higher concentrations of cells and intensity of immunohistochemical staining. The local differences between the cells that contain cystathionine ß-synthase were less pronounced than between other gaseous neurotransmitter interneurons. These data indicate that the internuclear interneurons have the structure that is necessary for the successful management of integration processes in the brain.

We performed a comparison of the characteristics of two cell-cycle proteins, viz., Cdk1 and Cyclin B1 (CycB1), in different brain regions of Yakut long-tailed ground squirrels (Spermophilus undulatus) at various stages of their hibernation cycle. The experiments were performed in the winter period (January to February) in four groups of animals that weighed 600–800 g, viz., animals entering hibernation (n = 9, brain T = 10°C); ground squirrels on the 6th–7th day of hibernation (n = 9, brain T = 1–2°C); animals that were awakened in the middle of hibernation at a brain temperature of 10°C (n = 6), and animals that were awakened at a brain temperature of 31–32°C (n = 8). The control group consisted of summer active animals (n = 8, brain T = 37–38°C) that were taken in mid-June to the beginning of July. We analyzed the mRNA and protein levels of Cdk1 and Cyclin B1 (CycB1) in the frontal cortex, hippocampus, cerebellum, and the caudal part of the brainstem. Our results indicate that the peak expression of Cdk1 mRNA in the frontal cortex, hippocampus, cerebellum, and caudal part of the brainstem of the hibernating animals occurred at different stages of their annual cycle, thus indicating region-specific regulation of Cdk1 mRNA in the brains of hibernating animals. A decreased Cdk1 protein level during hibernation (brain T = 1–2°C) in the hippocampus and the cerebellum, as compared to both the summer active phase (brain T = 37–38°C) and the late entrance into the hibernation phase (brain T = 10°C) indicates that the morphological plasticity of these structures is reduced in hibernating animals. Despite the overall low mRNA expression of Cdk1 and CycB1, the frontal cortex is characterized by synchronously high levels of Cdk1 (brain T = +10°C, p = 0.066) and CycB1 (brain T = 31–32°C, p = 0.014) proteins as compared to the hibernation period (brain T = 1–2°C). The Spearmen correlation between Cdk1 and CycB1 mRNA expression in the frontal cortex among all groups was p = 0.001, R = 0.65; in the cerebellum among all groups p = 0.010, R = 0.52. An increase in Cdk1 expression in the cortex and hippocampus of ground squirrels during a brain temperature increase from 1–2°C to 31–32°C reflects the development of morphological functional rearrangements that are crucial for either the development of new interneuronal connections or for restoration of old ones that are necessary for the integrative activity of the brain during dramatic changes in its functional state in the period of transition of the animals from hibernation to wakefulness.

Free-radical-mediated processes are involved in a variety of physiological events, while oxidative stress and related redox deregulation are implicated in various pathological events. Tripeptide glutathione plays an important role in the antioxidant defense of the brain, particularly in the maintenance of the optimal redox state in neurons and glial cells. We studied the combined effects of pantothenic acid derivatives, pantothenol and calcium pantothenate, and memantine, which is a glutamate receptor antagonist that is widely used for the treatment of dementia, on amnesia induced by scopolamine in rats. Scopolamine induced amnesia in rats; however, unexpectedly, this effect was even more expressed in the memantine-pretreated animals. Memory impairments were less manifested in the rats that were pretreated with memantine in combination with panthenol or calcium pantothenate. The detrimental scopolamine effect on memory was accompanied by significant depletions of glutathione and coenzyme A in the brain. While memantine recovered the glutathione status to some extent, it nevertheless further aggravated the scopolamine influence on coenzyme A levels. An alleviation of scopolamine-induced memory impairments that was observed after combined pretreatment with memantine and panthenol or calcium pantothenate was accompanied by a normalization of coenzyme A levels, while the effects on glutathione redox did not correlate with the behavioral data.

We studied the effect of carbon ions (¹²C) with an energy of 500 MeV/nucleon at a dose of 1 Gy on monoamine metabolism in the brains of rats of different ages. Neurochemical parameters that characterize the distribution of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and its metabolites were evaluated during 2 months on days 30 and 90 after the exposure to radiation. We studied the prefrontal cortex, hypothalamus, hippocampus, and striatum. The results showed changes in the activities of the NA, DA, and 5-HT systems in rats of different age groups after exposure to radiation. The most prominent differences in the exposed and control animals were observed in the prefrontal cortex and hypothalamus, which indicates the important role of these brain regions in long-term effects of exposure to radiation on the central nervous system. A comparison of animals from different age groups showed a decrease in the intensity of the temporal changes in all analyzed structures except the striatum in the exposed rats. Based on these findings, we assumed that the activation of compensatory and repairing mechanisms occurs in the late post-radiation period. At relatively low linear energy transfer of particles (10.6 keV/µm), it may lead to the partial recovery of brain functions that were impaired by radiation. At higher values of the linear energy transfer, the compensatory and recovery processes are activated to a lesser degree and functional impairment increases with time.

We studied the effect of thrombosis of retina vessels on the development of glutamate excitotoxicity in chinchilla rabbits. Thrombosis was induced by administration of Bengal rose dye at a dose of 40 mg/kg into the auricular vein of the animals followed by focal lighting with white light. Lighting was performed for 10 min on average at the temporal vascular arcade in the location of the angulation of vessels over the border of the disk of the optic nerve using a binocular ophtalmoscope and a condensing +14.0 D lens. We found that experimental thrombosis induced the accumulation of glutamate, aspartate, glycine, and GABA, as well as oxidative stress, which was associated with decreased activity of superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase.

Homocysteine (HCY) and other mediators of one-carbon metabolism have been blamed for the etiology of schizophrenia for a long time. The present study aimed to analyze the serum levels of HCY, methionine (MTY), vitamin-B12 (V-B12), folate (FLT), and glutathione (GSH) in schizophrenic patients and to search for new clues about the etiopathogenesis of this disease. The study included 62 schizophrenic patients (26 females and 36 males with a mean age of 33.79 ± 8.23 years) and 57 healthy control subjects (23 females and 34 males with a mean age of 33.66 ± 8.67 years). The serum levels of HCY and MTY were established using the LC/MS-MS method and the serum levels of V-B12, FLT and GSH were established using the ELISA method. The serum levels of HCY and MTY were significantly higher in the schizophrenia group compared to the control group. Again, the serum ratios of HCY/V-B12, HCY/FLT and MTY/V-B12 were significantly higher in the schizophrenia group than the control group. On the other hand, the serum levels of GSH and V-B12 were significantly lower in schizophrenic patients. The correlation analysis between V-B12 and HCY revealed a stronger negative correlation between HCY and V-B12 in schizophrenic patients than control group (r =–0.491, p < 0.001 for schizophrenic patients; r =–0.286, p = 0.03 for the control group). The present study is the first to evaluate the ratios of HCY/V-B12, HCY/FLT and MTY/V-B12 in schizophrenic patients. A defect in the V-B12 metabolism may increase the serum levels of HCY and MTY in schizophrenic patients.