Vol 54, No 3 (2018)

This review summarizes the literature data as well as experimental results obtained at our Institute over a period of 50 years on the substrate specificity of cholinesterases–acetylcholine acetylhydrolases (EC 3.1.1.7) and acylcholine acylhydrolases (EC 3.1.1.8). The parameters of enzymatic hydrolysis of oxo- and thiocholine and β-methylcholine esters in different organs and tissues were analyzed in 66 animal species including 22 chordate, 20 insect, 1 mite, 17 mollusk, 4 nematode, and 2 flatworm species. Our substrate specificity studies and extensive data on the inhibitory specificity obtained using irreversible organophosphorous inhibitors and reversible effectors unequivocally indicate that the cholinesterase family is characterized by a clear-cut species and tissue specificity.

The present study aimed to find out a link between ageing of rat and lamprey erythrocytes and activity of two isoforms of protein kinase C (PKC), РKСα and РKСζ. The whole cell population was separated into fractions of different ages in Percoll density gradient. The validity of separation was confirmed by the number of immature erythrocytes, reticulocytes. PKC activity was analyzed in cytosolic and membrane cell fractions. Rat erythrocytes express both PKC isoforms, РKСα and РKСζ, whereas lamprey erythrocytes express only РKСζ. РKСα is identified as a major band at ~ 80 kDa and minor bands at ~ 55–65 kDa; РKСζ is represented by a single band at ~ 80 kDa. In young rat erythrocytes, РKСα is detected mainly in cytosolic fractions, while in membrane fractions its level is by far lower. As cells age, PKCα is translocated from the cytosol to membranes and undergoes proteolytic degradation due to repeated cycles of activation. As a result, in aged erythrocytes relative total PKCα expression (as a sum of expressions in the cytosol and membranes per total protein level) diminishes, indicating a depletion of the PKCα pool and a decline in its functional activity. In both animal species, a highest PKCζ level is observed in the cytosol of young erythrocytes. Erythrocyte ageing is accompanied by a gradual decrease in expression of free cytosolic PKCζ and concurrent increase in the level of its membrane-bound forms. However, in contrast to PKCα, PKCζ is not proteolyzed; its total level in cells and perhaps functional activity do not change throughout the erythrocyte lifespan.

Clinical trials of insulin and experiments on its intranasal administration to animals suggest that this hormone can be efficient in treating human neurodegenerative and some other diseases associated with brain injury. However, the mechanism of the neuroprotective effect of intranasal insulin is far from being understood. The aim of the present work was to study the protective and antioxidative effects of insulin at various concentrations on rat brain cortical neurons under oxidative stress conditions and to estimate the contribution of protein kinase B (Akt) activity modulation to insulin-induced enhancement of neuronal viability in the rat brain cortex. The protective effect of insulin was shown to be dose-dependent within the nanomolar range (1 nM < 10 nM < 100 nM and/or 1 μM). A study of the antioxidative effect of insulin revealed the efficacy of such a low concentration as 1 nM. Immunoblot analysis showed that insulin at concentrations of 100 nM and 1 μM activates Akt both in neurons and control cells at different times after their exposure to a pro-oxidant agent. LY294002, a specific PI3K/Akt signaling pathway inhibitor, was shown to significantly reduce the protective and antioxidative effects of insulin. Insulin-induced upregulation both of Akt activity and antiapoptotic protein Bcl-2 appears to play an important role in the neuroprotective effect of insulin.

One of the old but still unsolved problems in psychiatry is the treatment of patients with a dual diagnosis of schizophrenia and alcoholism. Numerous clinical studies failed to explain unambiguously the mechanisms of formation of these comorbid disorders. Experimental modeling of dual disorders was carried out using a model of schizophrenia based on the impaired development and dopamine hypothesis of schizophrenia. To model comorbid experimental schizophrenia and alcohol abuse, the dopamine precursors, Levodopa/Carbidopa (LC), were used in combination with 15% ethanol. The aim of this study was to investigate social behavior of rats receiving LC and exposed to intermittent semi-compulsory alcoholization. After three months of the experiment, there were significantly more interactions (including aggressive–attacks, fights, bites) and submissive postures in the group of rats that received LC. Combined LC/ethanol administration did not alter rat social behavior in contrast to ethanol administered alone.

In everyday life, humans and animals occupying different rungs of the “evolutionary ladder” often have to evaluate the notions of larger/smaller size (predator/prey, rival/ally, etc.) and flat/volumetric shape (fruit/leaf, 2D/3D images, etc.). The aim of this study was to find out experimentally which of the following two tasks related to the formation of the preverbal notions of larger/smaller size or flat/volumetric shape is easier to train rhesus monkeys. The first task was to form or actualize the notion of larger or smaller size upon co-presentation of 4 flat or volumetric figures. The second task was to form or actualize the notion of flat or volumetric object among 4 figures of the same size (small, medium or large) presented simultaneously. To be rewarded during the formation of both notions, the animal was supposed to choose a figure which was different from the other three in the trial. In both tasks, the number of trials required to reach or exceed the 70% level of correct task implementation per each type of training was counted. This allowed optimization of the notion formation algorithm to rule out strong skill consolidation (overtraining) that might inhibit the formation of a new skill in further training. When the number of trials was averaged over all types of training, the notion of shape formed faster than the notion of size. This discrepancy was only observed under the difficulty of solving one of the task types–discriminating between objects poorly distinguishable (1.5 times) by their size. However, in the situation of no difficulty in discriminating between figures during their perception (more than a 2-fold difference in size), the number of trials in forming the notions of size and shape was statistically indistinguishable. Since training rates in forming the notions of larger/smaller size or flat/volumetric shape were indistinguishable in simple choice situations, we suggest that these notions are equally important for rhesus monkeys.