Stem cells research has passed a long and exciting way from the discovery to clinical applications. Every year more-and-more scientific reports and solid research breakthroughs are published in this fascinating field making it difficult to follow after new discoveries and cover the history. In the current review we overviewed history of stem cells research starting from the discovery and ending with the current state-of-art. We discussed obstacles and future perspectives of the cell-based therapy, with a special focus made on protection and regeneration of the lost functions after injury/degeneration of adult central nervous system.
The effect of 2-aminoethyl diphenylborinate (2-APB), a commonly used drug to modulate inositol-1,4,5-triphosphate (IP3) receptors and transient receptor potential (TRP) channels, on GABAA receptor-mediated currents was studied in neurons from the medial preoptic nucleus (MPN) of rat. 2-APB gradually and reversibly reduced the currents evoked by GABA but had no effect on the currents evoked by glycine. The blocking effect was not mediated by alterations in intracellular calcium concentration and showed a concentration dependence with half maximal effect at ~50 µM 2-APB, for currents evoked by 100 µM, as well as by 1.0 mM GABA, suggesting that 2-APB is not competing with GABA for its binding site at the GABAA receptor. Thus, the present study describes a novel pharmacological property of 2-APB as a non-competitive blocker of GABAA receptors and calls for caution in the interpretation of the results where 2-APB is used to affect IP3 receptors or TRP channels.
Malignant gliomas are primary brain tumors considered to be one of the deadliest cancers. Despite surgical intervention followed by aggressive radio- and chemo-therapies, average survival is approximately 15 months of diagnosis. Recurrent tumors resembling all the characteristics of the original tumor mass and growing in close vicinity to the original site are frequent due to presence of a self-renewing population of cells, glioma stem cells. The cells are resistant to therapies and able to invade the surrounding healthy brain tissue. Indeed, infiltrative growth assisted by numerous interactions with microenvironment are hallmarks of glioma growth. Many research efforts are put forward to understand the mechanisms of invasion. Glioma cells adopted numerous biological strategies to their own advantage to viciously propagate and navigate narrow spaces within the brain. Despite enormous amount of data on malignant gliomas generated by –omics approach which broaden our knowledge on glioma physiology in the last decade, parallel success in discovering new therapies did not happen. Thus, new therapeutic approaches may employ healthy cells of the microenvironment to tame malignant growth are necessary. Here, we highlight current knowledge on glioma origin, infiltrative growth, interactions with the microenvironment and potentials for new therapies.
Alzheimer’s disease (AD) is the most common cause of dementia with an increasing impact on the aging society. Although generations of researchers tried to unravel the pathomechanisms behind this disease, the molecular and cellular mechanisms leading to its onset and progression are still far from being completely understood. Accordingly, only a symptomatic treatment is available until now, and a curative treatment seems to be far-off. On the other hand, several novel therapeutic strategies have been proposed and debated during the last decade. Because of the extensive serotonergic denervation that has been observed in the AD brain and the important role played by serotonin in both, cognition and behavioural control, this neurotransmitter system has become a focus of a concerted research effort to identify new treatments for AD. Therefore, modulation of defined serotonin receptors by specific ligands represents a promising tool for treatments for neurodegenerative diseases like AD. Here we provide an overview of the involvement of the serotonergic system in AD and discuss the underlying molecular mechanisms.
The medial preoptic nucleus is critically involved in the social type of behavior regulation, such as parental behaviour, social recognition, sexual behaviour, ect.. A big amount of studies are focused on the role of glutamate, GABA, serotonin, and dopamine systems of medial preoptic area (mPOA) in the social types of behaviour regulation. However, the role of glycinergic system in this nucleus has not been investigated.
The aim of the investigation was to assess antihypoxic and neuroprotective properties of the glial cell line-derived neurotrophic factor (GDNF) in hypoxia models in vitro and in vivo. In vitro experiments were carried out on primary hippocampal cultures. Hypoxia modeling was performed on day 14 of culture development in vitro (DIV) by replacing the normoxic cultural medium with a medium containing low oxygen for 10 minutes. Registration of extracellular action potentials was conducted by MEA systems (Multichannel Systems, Germany) application. Study the effect of GDNF on synaptic plasticity was performed using SmartFlare RNA Detection Probes (Merck Millipore, France) and fluorescent microscopy. In vivo experiments were carried out on C57BL/6j male mice. For acute hypobaric hypoxia a vacuum flow-through chamber was used at the ambient temperature of 20–22°C. We have investigated the resistance of animals to hypoxia and their spatial memory retention in Morris water maze test 24 hours after hypoxia. In vitro and in vivo data demonstrated that GDNF has strong antihypoxic and neuroprotective properties. Preventive GDNF application before hypoxia contributed to the animal survival and spatial memory retention as well as the maintenance of cells viability in primary hippocampal cultures.
To identified genetic cause of congenital hypoplasia cerebellum in two families with different syndromes high- throughput sequencing analysis was performed. X-linked non-progressive ataxia in first family from Mongolian ancestry was caused by genetic defects in ABCB7 gene and modifying by ATP7A gene.
Today many fundamental questions in Neuroscience can be addressed with Microfluidics methods which provide unique approaches for cell patterning and control neural branch outgrowth. Such methods can be used to gwoe separate subpopulations of dissociated neurons connected with uni-directional connectivity. Combined with microelectrode arrays such approach can be used to simulate and study neurogenesis, learning and information coding in neural networks.
In this study we developed microfluidic structure with two neuronal cultures grown in separated chambers and connected by microchannels for axon outgrowth. We estimated bursting activity transfer characteristics between chambers in relation toculture development and determine rate of axonal growth in chambers.
The aim of the investigation was to study a role of cannabinoid receptors type 1 (СВ1) and type 2 (СВ2) in implementation of antihypoxic and neuroprotective effects of N-ADA in hypoxia model in vitro. The experiments were carried out on primary hippocampal cultures. N-ADA effect on the spontaneous bioelectrical and calcium network activity in dissociated hippocampal cultures in normal and hypoxic conditions as well as the role of CB1 and CB2 in the implementation of these effects were investigated. Registration of extracellular action potentials was conducted by MEA systems (Multichannel Systems, Germany) application. For the detection of patterns of spontaneous calcium oscillations we used fluorescent calcium dye Oregon Green 488 BAPTA-1 AM (Invitrogen) and a confocal laser scanning microscope (Zeiss LSM510, Germany). Study the expression of mRNA CB1 receptors was performed using SmartFlare RNA Detection Probes (Merck Millipore, France) and fluorescent microscopy. Our data demonstrated that N-ADA has strong antihypoxic and neuroprotective properties associated with activation of cannabinoid receptors type 1.