Vol 13, No 1 (2019)

Actin-binding proteins and, in particular, members of the actin-depolymerization factor (ADF)/cofilin family, are involved in the regulation of the actin cytoskeleton in response to various intracellular and extracellular signals. Recent studies point to the exceptional role of this group of proteins in the development and functioning of the nervous system. This review presents the latest data on the functions of cofilin in the cell and the signaling pathways involved in its regulation. Special attention is paid to studies of the relationship between cofilin and actin dynamics in such processes as the control of synaptic plasticity, apoptosis of neurons, and neuroinflammation. We show the molecular mechanisms of cofilin activation-inactivation and the specific structure of actin in nerve cells during neurodegeneration in the in vitro and in vivo models. We review new directions in the study of cofilin and related proteins as prognostic markers and therapeutic targets in the diagnosis and treatment of diseases of the nervous system.

Two cholinesterases were identified in the cotton bollworm Helicoverpa (Heliothis) armigera Hbn., that is, acetylcholinesterase from the nervous chain and butyrylcholinesterase from homogenates of larvae. A comprehensive study of the substrate-inhibitor specificity of cholinesterases (based on the modern concept of inhibition by high substrate concentrations), as well as the investigation of anti-enzyme action of 57 irreversible organophosphorus inhibitors, indicated a peculiarity of the enzymological characteristics of the bollworm cholinesterases compared to cholinesterases of arthropods and some mammals.

Excessive accumulation of dopamine (DA) in the cytosol, which becomes cytotoxic after oxidation, causes degeneration of dopaminergic (DA-ergic) neurons in Parkinson’s disease. The cytosolic DA content is a result of several processes, including vesicular deposition and DA reuptake. Taking this into account, in the present study we examined the expression of genes and proteins of type 2 vesicular monoamine transporter (VMAT2) and DA membrane transporter (DAT) in nigrostriatal DA-ergic neurons. We studied normal mice and mice with 29 or 59% degeneration of DA-ergic neurons induced by 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP), whose precursor is converted into a toxin in the brain. When extrapolating data from the study of the substantia nigra to the neuron, we showed that the degeneratSion of one-third of neurons resulted in the increased expression of the DAT gene in the surviving neurons and a reduced content of DAT; however, the expression of the gene decreased, while the content of VMAT2 increased. The decrease in the content of DAT and the increase in the content of VMAT2 indicate a decrease in DA reuptake and an increase in DA vesicular storage, which contributes to a decrease in cytosol accumulation of DA. Degeneration of a larger number of DA-ergic neurons was followed by an increased content of VMAT2, which indicates an increase in vesicular storage and an even greater reduction in the risk of cytosolic accumulation of oxidized DA. When extrapolating the data of the study in the striatum to the DA-ergic axon, we found that the content of DAT in the preserved axons did not change compared to the control, while the content of VMAT2 decreased, which indicates a decrease in vesicular storage of DA. Given the increased DA synthesis and the unchanged level of DA reuptake, a decrease in the content of VMAT2 should lead to the accumulation of oxidized toxic forms of DA in the cytosol.

Operative dysfunction of cosmonauts under the effects of space flight factors is the main limiting factor of interplanetary flights. Travel beyond the Earth’s geomagnetic field is associated with a significant increase in radiation hazard. Hypogravity is another space flight factor that influences CNS functions. It has previously been found that the impact of radiation and hypogravity may cause oppositely directed effects on CNS functions; their combined application may neutralize each other. Here, we have investigated the effects of hypogravity in an experiment with an antiorthostatic suspension and radiation with γ-rays and ¹²C⁺⁶ on the metabolism of serotonin and noradrenaline in morphological structures of the brain that are crucial for realization of stress-induced response in Long Evans outbred rats. The combined actions of the factors resulted in the dominant effect of radiation, which included enhancement of noradrenergic neurotransmission in the prefrontal cortex and attenuation of serotonergic neurotransmission within the prefrontal cortex and amygdala. No changes were found in the hypothalamus. Therefore, we did not find any changes in serotoninergic and noradrenergic neurotransmission that are typical of the stress-induced response.

The effect of α₂-adrenoblocker mesedin (2-(2-methylamino-4-thiazolyl)-1,4-benzodioxane hydrochloride) on the content of oxidative stress biomarkers in the brain tissue was well studied in ischemic disorders. The aim of this study is to reveal the possible mechanisms of the antihypoxic effect of mesedin. The quantitative changes of the final product of lipid peroxidation (LP)—malondialdehyde (MDA) and carbonyl derivatives of proteins — aldehyde-dinitrophenylhydrazones of neutral character (ADNPuv), ketone-dinitro-phenylhydrazones of neutral character (KDNPuv), aldehyde-dinitrophenylhydrazones of basic character (ADNPvs) and ketone-dinitrophenylhydrazones of basic character (KDNPvs) were studied in the brain tissue of rats (n = 56) under the condition of experimental ischemia caused by the ligation of the right common carotid artery. The study showed that one of the possible mechanisms of antihypoxic action of mesedin is its ability to prevent the accumulation of malondialdehyde and to limit protein carbonylation in brain ischemia. The data received demonstrates that mesedin could serve as a potential medicine for the correction of cerebrovascular ischemic disorders, for the reason that along with improving cerebral blood flow and preventing the development of morphological shifts and neurobehavioral disturbances in brain local ischemia, the medicine also mitigates the aggressive action of oxidative stress while protecting the brain tissue from the consequences of hypoxia.

Inhibitory GABAergic and excitatory glutamatergic neurons from multiple brain areas, send fibers to the hippocampal CA1 region. NMDA receptors have been identified as important compoents of the brain system underlying memory formation, which that through an increase in glutamate-mediated neurotransmission. Ketamine and other NMDA receptor antagonists produce deficits in cognitive tasks, including both spatial and non-spatial memory. In the current study, we tested whether the activation or inhibition of GABA_A receptors in CA1 hippocampal of mice has an impact on ketamine (NMDA antagonist) induced spatial and non-spatial novelty detection deficits. Adult male mice weighing between 25–30 g were used. The open-field method was used to evaluate spatial and non-spatial memory information. Data obtained from the present study revealed that an intra-CA1 injection with a sub-threshold dose the GABA_A receptor antagonist bicuculline (0.0625 µg mouse) disrupted spatial memory but restored non-spatial memory induced by lower and higher doses of ketamine (0.05 and 0.01 mg/kg) respectively. Meanwhile, the co-administration of the intra-CA1 injection with a sub-threshold dose of muscimol (GABA_A receptor agonist at 0.25 µg/mouse) and a lower dose of ketamine could only impair the ability of non-spatial change detection but could not alter spatial novelty. In conclusion, ketamine (which contributes to the impairment of memory trace stored in the hippocampus) may be generated from GABA_A receptors of CA1 neurons and their blockade could prevent these effects.

Alzheimer’s disease (AD) is a problematic disease that has shown a significant increase in patient numbers worldwide. AD is identified pathologically by the accumulation of the toxic amyloid beta (Aβ) protein, neurofibrillary tangles and neuropil threads in postmortem brains of AD patients. Women are more prone to AD either due to their increased life expectancy or the decline in Estrogen hormone levels around menopause. Estrogens play a physiologically important role in the brain, but there is debate about the association between estrogen and Ad. The neuroprotective effects of estrogens are possibly mediated by estrogen receptors (ERs), which include classical nuclear estrogen receptors (ER_α and ER_β) and nonclassical ER (G protein-coupled estrogen receptor 1, GPER1(GPR30)). The effect of GPER1 on Aβ-induced neurotoxicity is unclear. Here we studied the effect of GPER1 receptor agonists G-1 on rat neuronal cells. Rat neuronal cells were incubated with Aβ_1–42, either alone or in combination with GPER1 agonist G-1 (10⁻⁷, 10⁻⁸ and 10⁻⁹ M). Cell viability was determined by MTT assays and apoptotic effects induced by Aβ_1–42 were measured by Cell Death Detection kit. Oxidative stress parameters, including nitric oxide (NO) levels and total oxidant status (TOS) were measured by spectrophotometry. Approximately half of the cell death was observed with 10⁻⁶ M Aβ_1–42 incubation for 48 hours. This is the first study that explores the effect of activation of GPER1 by its agonist G-1 on neuroprotection against Aβ_1–42-toxicity in rat neuronal cells. GPER1 activation significantly reduced on rat neuronal cells. Aβ_1–42 induced cell death was significantly reduced by co-incubating with G-1. Our results suggest that G-1 treatment protects neurons from Aβ_1–42 induced neurotoxicity by changing the oxidative parameters on rat neuronal cells.