Vol 13, No 3 (2019)

Abstract—Development of the technology of induced pluripotent stem cells (iPSC) opened new opportunities for studies of the mechanisms of pathogenesis and effective treatment of acute and chronic forms of cerebral pathologies. Here, we review current literature data on the use of the iPSC technology for in vitro modeling of Alzheimer’s disease, search for new pharmacological drugs for its treatment, and modern approaches to neurotransplantation for personalized cellular therapy.

Abstract—This review summarizes the current understanding of the regulatory role of melatonin in the formation of the nervous system in the antenatal and early postnatal period of body development. We discuss questions concerning the involvement of melatonin and the suprachiasmatic nuclei of the hypothalamus, which are the central oscillator of biorhythms, in the synchronization of the functions of various body systems. The mechanisms of protection of the developing brain from the damage caused by oxidative stress and inflammation are discussed. We presented a detailed list of biomarkers of this process, whose analysis may help to evaluate disturbances of the cognitive functions in early ontogeny, which often have remote consequences. Special attention is paid to the neuroprotective effect of melatonin on offspring during hyperhomocysteinemia, which disturbs epigenetic regulation by affecting the methylation processes (methyltransferase activity) in the nervous system and entire body. This material justifies the prospects for the use of melatonin in clinics for the treatment of disorders of the functional activity of the brain of the fetus and newborn.

Abstract—We studied the effect of a 2-week administration of cycloprolylglycine peptide (CPG) (1 and 2 mg/kg/day, i.p.) on the binding characteristics of serotonin 5-HT_2A-, NMDA-, metabotropic glutamate mGluII-, GABA_A- and GABA_B-receptors in the brain of inbred BALB/c mice in vitro and ex vivo. It was found that CPG at doses of 1 and 2 mg/kg/day reduces the density of 5-HT_2A receptors in the striatum of mice by 24 and 28%, respectively. A decrease in the density of NMDA receptors in the hippocampus was observed only at a dose of 2 mg/kg/day; it was 22%. At the same time, there was an increase in the density of GABA_A receptors in the frontal cortex at a dose of 1 mg/kg/day by 36% compared with the control. The 2-week administration of CPG at both doses did not affect B_max of mGluII- and GABA_B receptors, as well as K_d in all groups. In the in vitro radioligand assay, the CPG did not affect the specific binding of the labeled ligands of the studied receptors. These data indicate the functional involvement of 5-HT_2A, NMDA, and GABA_A receptors in the formation of the antidepressant-like effect of cycloprolylglycine in BALB/c mice for the first time.

Abstract—We studied the effects of the potential antiepileptic agent GIZh-298 and a comparison drug, topiramate, on the concentration of monoamines and their metabolites in the frontal cortex, hypothalamus, nucleus accumbens, striatum, and hippocampus in the rat brain after generalized tonic–clonic seizure caused by electroshock (MES). We found that GIZh-298 (60 mg/kg, i.p.) exhibits a pronounced anticonvulsant effect in the test of MES antagonism and prevents the increase in functional activity of the dopaminergic system and the reduction of the norepinephrine (NE) content in the same structure. Topiramate (100 mg/kg, i.p.), as well as the GIZh-298, prevented the emergence of MES-induced seizures and stimulated an increase in the NA level in the striatum to the normal values but did not affect the MES-induced changes in the functional activity of the dopaminergic system of the nigrostriatal system. Therefore, it may be concluded that the modulation of the noradrenergic neurotransmission in the striatum is one of the mechanisms of the anticonvulsant effect of both GIZh-298 and topiramate in the test of MES antagonism and, in addition, GIZh-298, unlike topiramate, contributes to the reduction of the functional activity of the dopaminergic system in this structure in response to MES.

Abstract—The purpose of this investigation was to study the neurobiological effects of several interplanetary flight factors: hypogravity, which was modeled in a ground-based experiment using the conventional gravitational unloading technique, a 7-day anti-orthostatic hanging (AOH), and synchronous with it long-term gamma irradiation and high-energy protons. We analyzed the animal behavior in a number of tests: the open field, elevated plus maze, passive avoidance, Morris water test, and the exchange of monoamines in key brain structures. The most interesting and paradoxical result of our study is that in some cases effects were mitigated by the combined effect of radiation and microgravity, which manifests itself both in behavior and in neurochemical changes in all five studied brain structures, despite the fact that these structures play different roles in the performance of behavior. However, the isolated treatment with both radiation and AOH caused significant changes.