Purinergic Signaling in Neuroinflammation

ATP is stored in millimolar concentrations within the intracellular medium but may be released to extracellular sites either through the damaged plasma membrane or by means of various transporters. Extracellular ATP or its enzymatic breakdown products, ADP, AMP, and adenosine, may then stimulate a range of membrane receptors (Rs). These receptors are classified as belonging to two types termed P2 or P1. P2Rs can be, in addition, subdivided into the ligand-activated P2X and the G protein-coupled P2Y types. Adenosine acts on the P1 type of receptor. A further classification identifies seven mammalian subtypes of P2X1-7 and eight mammalian subtypes of P2YRs (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, P2Y14). P1Rs are either positively (A2A, A2B) or negatively (A1, A3) coupled to adenylate cyclase via the respective G proteins. Already, such a high number of receptors suggests that purine-mediated effects at the cellular but especially whole organism level have an immense variability. Whereas P2XRs respond only the ATP, P2YRs are sensitive to ATP/ADP, UTP/UDP, or UDP–glucose. Inspection of some articles in this Special Issue will teach us that the nucleoside guanosine probably possesses a receptor of its own, that nucleotides can be gradually degraded metabolically to functionally active nucleotides/nucleosides (see above), and indirect effects by stimulating the synthesis or decomposition of purines/pyrimidines may also increase functional diversity. Eventually, P2/P1Rs may interact both with each other as well as with other neurotransmitter receptors. It is, of course, important to note that, in many cases, receptor (sub)type-preferential agonists and highly selective antagonists are available for pharmacological analysis

Scientometrics: Untangling the topics

Measuring science is based on comparing articles to similar others. However, keyword-based groups of thematically similar articles are dominantly small. These small sizes keep the statistical errors of comparisons high. With the growing availability of bibliographic data such statistical errors can be reduced by merging methods of thematic grouping, citation networks and keyword co-usage.Comment: 2 pages, 2 figure

Pathological ATPergic Signaling in Major Depression and Bipolar Disorder

The mood disorders, major depression (MD) and bipolar disorder (BD), have a high lifetime prevalence in the human population and accordingly generate huge costs for health care. Efficient, rapidly acting, and side-effect-free pharmaceuticals are hitherto not available, and therefore, the identification of new therapeutic targets is an imperative task for (pre)clinical research. Such a target may be the purinergic P2X7 receptor (P2X7R), which is localized in the central nervous system (CNS) at microglial and neuroglial cells mediating neuroinflammation. MD and BD are due to neuroinflammation caused in the first line by the release of the pro-inflammatory cytokine interleukin-1b (IL-1b) from the microglia. IL-1b in turn induces the secretion of corticotropin-releasing hormone (CRH) and in consequence the secretion of adrenocorticotropic hormone (ACTH) and cortisol, which together with a plethora of further cytokines/chemokines lead to mood disorders. A number of biochemical/molecular biological measurements including the use of P2X7R- or IL-1b-deficient mice confirmed this chain of events. More recent studies showed that a decrease in the astrocytic release of ATP in the prefrontal cortex and hippocampus is a major cause of mood disorders. It is an attractive hypothesis that compensatory increases in P2X7Rs in these areas of the brain are the immediate actuators of MD and BD. Hence, blood-brain barrier-permeable P2X7R antagonists may be promising therapeutic tools to improve depressive disorders in humans

Considerations of Regional Coherences for the Development of Renewable Energy Technologies Used in South Part of Transdanubian Region of Hungary

Abstract The existing effective domestic regional development framework requires analyses for increasingly wider areas (micro, meso and even macro regions) before operational – short-term – local developments to be prepared and implemented. Such comprehensive complex studies or larger-term programmes may demonstrate the profitability of the given project and can complement it with combined utilization technologies; in the case of Himesháza several locally known renewable energy sources could facilitate geothermal heat, later electricity supply, e.g. local biomass (biogas-based) recovery technology (organic waste of the local pig farm) and, for example, the construction of a low-power “dwarf” hydroelectric power plant chain based on rich watercourses of the region (the “southern dwarves” in Hungary) and the connection of existing solar utility facilities to a modern “smart grid” system in the longer term. Himesháza, located in southern Hungary in Baranya county, is developing; it has a detailed feasibility study of a thermal energy supply network and an energy supply development plan. Based on the geothermal characteristics of Baranya county it would be reasonable to encourage the development of smaller-scale, decentralized heating systems for dynamic settlements. Several settlements in close proximity to Himesháza have already explored thermal wells. Power generation with a small scale, closed-loop system can be used in the project region for thermal water with an outflow temperature of 90 °C. The heating system may also be able to fulfill the needs of recreational, vacation-based or complex thermal spa facilities formerly planned in the region. Moreover, the system could also be capable of utilizing a larger spectrum of renewable energy through its combination with photovoltaic technology. Due to the country's favorable agricultural characteristics, Hungary's biomass potential is higher than the European average. The utilization of organic waste from agricultural and farming sectors is highly recommended in Baranya county; biogas production seems to be the most suitable in the region of Himesháza too, broadening the utilization of renewable resources. The realization of the current project could contribute to shifting the energy resource sector in a more modern, environmentally conscious direction. The background for shorter-term plans and investment (carried out within the framework of operational programs) necessary for the optimal operation and maintenance of longer-term (25–50 years) energy development strategies is created by the analysis (at multiple scales) of complex regional characteristics and future potential, and the selection of optimal sites

Astrocytic and Oligodendrocytic P2X7 Receptors Determine Neuronal Functions in the CNS

P2X7 receptors are members of the ATP-gated cationic channel family with a preferential localization at the microglial cells, the resident macrophages of the brain. However, these receptors are also present at neuroglia (astrocytes, oligodendrocytes) although at a considerably lower density. They mediate necrosis/apoptosis by the release of pro-inflammatory cytokines/chemokines, reactive oxygen species (ROS) as well as the excitotoxic (glio)transmitters glutamate and ATP. Besides mediating cell damage i.e., superimposed upon chronic neurodegenerative processes in Alzheimer’s Disease, Parkinson’s Disease, multiple sclerosis, and amyotrophic lateral sclerosis, they may also participate in neuroglial signaling to neurons under conditions of high ATP concentrations during any other form of neuroinflammation/neurodegeneration. It is a pertinent open question whether P2X7Rs are localized on neurons, or whether only neuroglia/microglia possess this receptor-type causing indirect effects by releasing the above-mentioned signaling molecules. We suggest as based on molecular biology and functional evidence that neurons are devoid of P2X7Rs although the existence of neuronal P2X7Rs cannot be excluded with absolute certainty

The Anti-Inflammatory Astrocyte Revealed: the Role of the Microbiome in Shaping Brain Defences

Astrocytes are a sub-type of neuroglia responsible for homoeostasis and defence of the nervous system. Pathological reactions of neuroglial cells in various neurological disorders have been identified and characterised in the end of the 19th century; in particular hypertrophy of astrocytes was recognised as a frequent morbid change accompanying diseases of the central nervous system (CNS).This work was supported by grants of the National Key R&D Programme of China (2019YFC1709101) and the Project First-Class Disciplines Development of Chengdu University of Traditional Chinese Medicine (CZYHW1901) awarded in order to build up the “International Collaborative Centre on Big Science Plan for Purinergic Signalling”, and the Science and Technology Programme of Sichuan Province, China (2019YFH0108). The stay and work of PI in Chengdu was supported by a grant from the State Administration of Foreign Experts Affairs (G20190236012). A.S. and Y.T. are supported by RFBR grant 21-54-53018 for the NSFC-RFBR projec