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Plasmids containing four GFP-tagged isoforms of the human GDNF gene, with both pre- and pro-regions ( pre- pro- GDNF), with the pre- ( pre- GDNF) or the pro-region ( pro- GDNF) alone, and without the pre- and pro-regions (m GDNF), were used to transfect HEK293 cells (human embryonic kidney cell line). The effect of the transgenic products on the growth of processes was studied in the spinal ganglia of 14-day rat embryos. Media conditioned by the transgenic cells were used to culture explants and dissociated cells of embryonic dorsal root ganglia attached to the bottom of the plate. Medium conditioned by gfp-transgenic HEK293 cells was used as the control. Spinal ganglia explants and dissociated cells cultured in a medium supplemented with recombinant GDNF (recGDNF) as well as in conditioned media containing the pre-GDNF and mGDNF products demonstrated active growth of processes immunopositive for neuronal marker beta-3-tubulin as early as on culture day 4. The ganglia and cells cultured in control medium and media conditioned by cells transgenic for pro-GDNF had no or very few processes even after 10 days of culture. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the ability of Alphitobius diaperinus homogenates immobilized on plant sorbent to block the development of mouse parkinsonism. The materials and methods used in the study is discussed. The study found that the Alphitobius diaperinus homogenate immobilized on a plant sobent demonstrated its ability to neutralize the effect of the methylphenyltetrahydropyridine (MPTP) toxin on mice.

Using immunoblotting, we showed that in rats of audiogenic epilepsy (AE) prone strain (Krushinsky-Molodkina, KM) the superior colliculus tissue (SC) contains significantly less quantity of glial neurotrophic factor (GDNF), beta-tubulin and actin in comparison to the same brain region in "0" rats, nonprone to AE. This fact led to the suggestion that the histological structure of the SC in KM rats could differ significantly from that of the "0" strain. Using neuromorphology technique, we demonstrated that the total number of SC cells, as well as the number of neurons were significantly less in KM rats than in the "0" strain rats. Particularly strong differences were found in the deep layers of SC, the area of terminals from IC. Further studies of the midbrain structures, will help to identify the novel aspects of neural networks, involved in the genesis of AE in rats of KM strain. [ABSTRACT FROM AUTHOR]

The activation of genetic constructs including the Drosophila hsp70 promoter with four and eight HSE sequences in the regulatory region has been described in human cells. The promoter was shown to be induced at lower temperatures compared to the human hsp70 promoter. The promoter activity increased after a 60-min heat shock already at 38°C in human cells. The promoter activation was observed 24 h after heat shock for the constructs with eight HSEs, while those with four HSEs required 48 h. After transplantation of in vitro heat-shocked transfected cells, the promoter activity could be maintained for 3 days with a gradual decline. The promoter activation was confirmed in vivo without preliminary heat shock in mouse ischemic brain foci. Controlled expression of the Gdnf gene under a Drosophila hsp70 promoter was demonstrated. This promoter with four and eight HSE sequences in the regulatory region can be proposed as a regulated promoter in genetic therapeutic systems. [ABSTRACT FROM AUTHOR]

Experimental data were reviewed which demonstrated that the neonatal injection effects of certain biologically active drugs (ACTH fragment and its analogue Semax, piracetam, caffeine, levetiracetam, busperone, etc.) could be detected in adult animals as changes in physiological and behavioral reactions and in several morphological traits as well. Audiogenic seizures proneness, anxiety-fear and exploration behavior as well as pain sensitivity were analyzed. The remote effects discovered were either similar in direction to those applied to an adult organism, or opposite to it. Pharmacological treatments of such type presumably interfere the CNS development during early postnatal ontogeny and change the normal pattern of brain development. These modulatory influences could be due to changes in neurotransmitter system development and are presumably capable to induce CNS morphological deviations (numbers of neurons, adult neurogenesis). [ABSTRACT FROM AUTHOR]

Background: A number of epidemiological studies have established a link between insulin resistance and the prevalence of depression. The occurrence of depression was found to precede the onset of diabetes and was hypothesized to be associated with inherited inter-related insufficiency of the peripheral and central insulin receptors. Recently, dicholine succinate, a sensitizer of the neuronal insulin receptor, was shown to stimulate insulin-dependent H2O2 production of the mitochondrial respiratory chain leading to an enhancement of insulin receptor autophosphorylation in neurons. As such, this mechanism can be a novel target for the elevation of insulin signaling. Results: Administration of DS (25 mg/kg/day, intraperitoneal) in CD1 mice for 7 days prior to the onset of stress procedure, diminished manifestations of anhedonia defined in a sucrose test and behavioral despair in the forced swim test. Treatment with dicholine succinate reduced the anxiety scores of stressed mice in the dark/light box paradigm, precluded stress-induced decreases of long-term contextual memory in the step-down avoidance test and hippocampal gene expression of IGF2. Conclusions: Our data suggest that dicholine succinate has an antidepressant-like effect, which might be mediated via the up-regulation of hippocampal expression of IGF2, and implicate the neuronal insulin receptor in the pathogenesis of stress-induced depressive syndrome. [ABSTRACT FROM AUTHOR]

Published data and our own results on the identification, cultivation, and potential therapeutic utilization of regional stem cells from humans and animals are reviewed. Pluripotent stem cells have been shown to proliferate in the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampal formation in adult human and animal brains. Data on the hierarchical organization of genetic networks in controlling individual development suggest a possible functional role for repeat mini-and microsatellite DNA sequences in stem cell differentiation. Methods of using human bone marrow as a source of stem cells for restoring damaged tissue in the brain are discussed. Heat-shock proteins have been found to block the formation of glial scars after neural transplantation. The viability of stem cells after transplantation can be increased by transfer of genes for neurotrophic growth factors into the genomes of the neurons undergoing transplantation. [ABSTRACT FROM AUTHOR]

Abstract The fate of human fetal stem/progenitor cells transplanted into rat brain depends on conditions of preculturing (long or short) and state and site of transplantation. Human nestin-positive stem cells cultured according to the short protocol did not migrate into hypoxic and normal brain after transplantation, but actively migrated in damaged spinal cord. After transplantation of long-cultured cells into the brain mainly committed neuroblasts and solitary nestin-positive cells migrated from the site of transplantation into the brain. [ABSTRACT FROM AUTHOR]

Abstract We studied the effect of culturing conditions on the fate of human neural stem cells after transplantation into rat brain. Human neural stem cells cultured in the presence of mitogens without LIF migrated along the ependyma and cerebral vessels of recipients, but to a great extent degenerated by the 20th day after transplantation. Neural stem cells cultured with LIF migrated, apart from the above mentioned pathways, in the cortex and hippocampus, well survived; proliferating cells were retained 30 days after transplantation. [ABSTRACT FROM AUTHOR]

The aim of the present work was to study human neural stem/progenitor cells (SPC) cultured in vitro and their potential to survive, migrate, and differentiate after transplantation into adult rat brain. SPC were extracted from the brains of nine-week human embryos and were cultured in selective medium for three weeks. Transplantation was with suspensions of cells or whole neurospheres; these were studied four weeks after transplantation into the hippocampus, striatum, and lateral ventricles of adult rats. Analysis of transplanted cells was based on various histological and immunohistological staining methods: bisbenzimide, bromodeoxyuridine, and antibodies to human nuclei, vimentin, β-tubulin, neurofilaments, and glial fibrillar acidic protein, which allowed us to make independent assessments of their state and differentiation. Transplanted SPC from human brains survived well for one month in all areas of adult rat brain without immunosuppression. Cells from suspension transplants migrated intensely and differentiated into neurons and gliocytes. At the same time, transplants of whole neurospheres showed limited or no migration because of the development of a glial barrier. [ABSTRACT FROM AUTHOR]

Transplants of cultured neural stem cells from human brain survived, retained multipotent activity, and produced a neuroprotective effect on degenerating neurons in the brain of adult rats subjected to hypoxic hypoxia. They normalized animal behavior and improved conditioning in two-way avoidance response paradigm in a shuttle box. [ABSTRACT FROM AUTHOR]

Neural stem cells of human brain were cultured for a long time and successfully transplanted into the brain of rats exposed to acute hypoxia. Stem and committed cells, neuroblasts, and astrocytes were revealed in transplants by immunohistochemical assay. The transplants and brain tissue were not separated with a glial barrier. Human neuroblasts widely migrated into regions of neuronal degeneration in the host brain. [ABSTRACT FROM AUTHOR]

The review presents data which provides evidence for the internal relationship between the stages of rodent audiogenic seizures and post-ictal catalepsy with the general pattern of animal reaction to the dangerous stimuli and/or situation. The wild run stage of audiogenic seizure fit could be regarded as an intense panic reaction, and this view found support in numerous experimental data. The phenomenon of audiogenic epilepsy probably attracted the attention of physiologists as rodents are extremely sensitive to dangerous sound stimuli. The seizure proneness in this group shares common physiological characteristics and depends on animal genotype. This concept could be the new platform for the study of epileptogenesis mechanisms. [ABSTRACT FROM AUTHOR]

GABAergic brain system is an important link in the pathological circuits of rodent audiogenic epilepsy (AE). The number of GABAergic neurons in the inferior colliculi of KM strain rats (AE prone) was not different from that of the control non-prone strain. At the same time, the glutamate decarboxylase mRNA expression (the key enzyme of GABA synthesis) was 5 times higher than in control. The data evidence that the GABAergic system does play an important role in AE proneness. [ABSTRACT FROM AUTHOR]

Background: High-grade gliomas remain a virtually incurable form of brain cancer. Current therapies are unable to completely eradicate the tumor, and the tumor cells that survive chemotherapy or radiation therapy often become more aggressive and resistant to further treatment, leading to inevitable relapses. While the antiproliferative effects of new therapeutic molecules are typically the primary focus of research, less attention is given to their influence on tumor cell migratory activity, which can play a significant role in recurrence. A potential solution may lie in the synergistic effects of multiple drugs on the tumor. Objectives: In this study, we investigated the effect of combined exposure to bi-(AID-1-T), an anti-proliferative aptamer, and its analog bi-(AID-1-C), on the migratory activity of human GBM cells. Results: We examined the effects of various sequences of adding bi-(AID-1-T) and bi-(AID-1-C) on five human GBM cell cultures. Our findings indicate that certain sequences significantly reduced the ability of tumor cells to migrate and proliferate. Additionally, the expression of Nestin, PARP1, L1CAM, Caveolin-1, and c-Myc was downregulated in human GBM cells that survived exposure, suggesting that the treatment had a persistent antitumor effect on these cells. [ABSTRACT FROM AUTHOR]

Abstract Cultured mouse embryonic stem cells can be transfected with a reporter gene encoding blue fluorescent protein BFP and regulated by drosophila heat shock protein 70 promoter. This gene is activated after heating and synthesizes matrix RNA. Blue protein is synthesized under these conditions. The system for transfection of stem cells allows us to activate automatically the corresponding transgenes. [ABSTRACT FROM AUTHOR]