Том 10, № 3 (2016)

We review the transport systems of the monoamines dopamine, noradrenaline, and serotonin, which are localized in cytoplasmic membranes and the membranes of synaptic vesicles. We present information on the structure of the transporters and the mechanisms of their functioning. Ligands of the transport systems of monoamines include medications and drugs with psychostimulatory action. The most important neurochemical characteristics of ligands of monoamine transport systems is their affinity to transporters and the ability to inhibit reuptake of neuromediators or, in contrast, initiate a reverse current of neurotransmitters. This is the basis of the pharmacological activities of the considered substances.

The effects of serotonin and glutamate applications on H3 histone phosphorylation at serine 10 (Ser10, pHisH3) were immunohistochemically studied in the nuclei of L-RPa2-3 defensive behavior command neurons in the snail Helix lucorum. We found that simultaneous application of neurotransmitters induces biphasic changes in pHisH3-immunoreactivity in RPa2 neurons. The pHisH3 content increased at 30 min and decreased at 3 hours below the initial level, whereas in RPa3 neurons, a decrease in pHisH3 at 3 h occurred. Changes in pHisH3-immunoreactivity were not found in LPa2 and LPa3 neurons during the 7 hours of the experiment. Alterations of pHisH3-immunoreactivity in neural nuclei coincided with significant changes in colocalization with DNA. Our results demonstrate neuron-specific changes in genome activity in the neural nuclei of identified neurons in a cell model of a simple form of learning.

In this study, we investigated the activities of several antioxidant enzymes during the postnatal development of the brain and liver of rats. Experiments were performed on male rats of different ages, viz., 5, 10, 20, 30, and 90 days, so that the different periods of the brain development could be investigated. The activity of the enzymes of the antioxidant system (superoxide dismutase, catalase, and glutathione peroxidase) in the immature brain was found to be lower than in the brains of adult animals. Cytoplasmic superoxide dismutase was an exception: its activity declined along with development in both brain and liver. High activity of antioxidant enzymes on day 5 of postnatal development in rats was found, which may be associated with the adaptation to the environment with increased oxygen content. Our results led to the conclusion that the formation of the antioxidant system in the postnatal development of the brain is accompanied by redistribution of the enzyme activity between subcellular fractions, as well as changes in the contributions of the main pathways of Н₂О₂ elimination: the activity of glutathione system enzymes increases and the catalase activity decreases.

Degradation of the dopaminergic nigrostriatal system is a central process of the pathogenesis of Parkinson’s disease, which is a chronic neurodegenerative disorder. A specific feature of the disease is longterm asymptomatic progress over decades, which occurs due to the functioning of compensatory processes in the brain. Specific motor symptoms appear after substantial lesion of the nigrostriatal system and depletion of compensatory reserves. At this stage, traditional treatment of patients has low efficiency. In the present study, we developed new neurotoxic models of the maximally prolonged preclinical stage and early clinical stage of Parkinson’s disease in mice and performed a thorough evaluation of motor behavior and the morphofunctional state of the nigrostriatal system in these animals. Further comparative study of these models will help to identify: (a) specific peripheral biomarkers of each stage as a basis for the development of the early preclinical diagnostics of Parkinson’s disease; (b) the mechanisms of neuroplasticity that are responsible for asymptomatic progress of the disease; (c) molecular triggers of impaired motor behavior during the transition from the preclinical stage to the clinical stage.

We have shown that the protective effect of the prolonged (18 hours) incubation of cortical neurons with alpha-tocopherol (alpha-T) prior the action of H₂O₂ depends on the concentration in the nanomolar range (100 nM > 10 nM > 1 nM). The higher concentrations of alpha-T (1, 10, and 100 μM) increased the viability of cortical cells approximately equally to 100 nM alpha-T. We found that H₂O₂ has little effect on the concentration of the anti-apoptotic protein Bcl-2 in mitochondria of the neurons of the cerebral cortex during the first hours of its impact, but causes a dramatic decrease in its level in 12 and 24 hours after the start of its effect in comparison with the baseline values. If neurons are subjected to a prolonged (18 hours) preincubation with 100 nM or 100 μM alpha-T, the concentration of Bcl-2 12 and 24 hours after the application of H₂O₂ do not differ from the control values; however, it is higher than the concentration of Bcl-2 in neurons after exposure to H₂O₂ only. The level of the proapoptotic protein Bax in cortical neurons did not undergo prominent changes in the presence of H₂O₂ and alpha-T. A pronounced significant increase in the Bax/Bcl-2 ratio was found in neurons of the cerebral cortex at 12 and 24 hours after the start of the H₂O₂ effect on neurons of the cerebral cortex. Such prolonged incubation of neurons with 100 nM and 100 μM alpha-T prior to the H₂O₂ application normalizes these parameters and reduces the Bax/Bcl-2 ratio to the control values.

We measured the contents of brain-derived neurotrophic factor (BDNF) in the lacrimal fluid, aqueous humor, and blood serum in 40 patients (40 eyes) with age-related cataracts. Collection of stimulated lacrimal fluid was performed by a pipette on the day preceding surgery; the aqueous humor and the blood were sampled during the phacoemulsification of a cataract. BDNF was measured using an enzyme immunoassay. On average, the concentration of BDNF in patients was 121.2 ± 47.7 pg/mL in the lacrimal fluid, 52.2 ± 25.7 pg/mL in the aqueous humor, and 23418 ± 7645 pg/mL in the blood serum. The concentration of BDNF in the aqueous humor correlated well with its content in the lacrimal fluid (Pearson’s correlation coefficient was 0.61, P < 0.000) and was below it by a factor of 0.44 ± 0.19 on average. The data we obtained may be used for an approximate evaluation of the BDNF concentration in the aqueous humor on the basis of an analysis of the lacrimal fluid.

We have performed a quantitative analysis of temporal pattern of immunohistochemical staining to PCNA and Dcx in brain tissue under the influence of 10% neutral buffered formalin (fixation for 3.5 h–7 weeks). After 7 days of fixation we found a decrease in Dcx and, to a lesser extent, PCNA immunoreactivity. Later, no further decline in immunoreactivity occurred. Our data may be useful for optimization of neurogenesis assessment protocols in mammalian and human brains.