Astrocyte glutamine synthetase : pivotal in health and disease

The multifunctional properties of astrocytes signify their importance in brain physiology and neurological function. In addition to defining the brain architecture, astrocytes are primary elements of brain ion, pH and neurotransmitter homoeostasis. GS (glutamine synthetase), which catalyses the ATP-dependent condensation of ammonia and glutamate to form glutamine, is an enzyme particularly found in astrocytes. GS plays a pivotal role in glutamate and glutamine homoeostasis, orchestrating astrocyte glutamate uptake/release and the glutamate-glutamine cycle. Furthermore, astrocytes bear the brunt of clearing ammonia in the brain, preventing neurotoxicity. The present review depicts the central function of astrocytes, concentrating on the importance of GS in glutamate/glutamine metabolism and ammonia detoxification in health and disease

Filming the glial dreams: real-time imaging of cannabinoid receptor trafficking in astrocytes

How does the brain process incoming information and produce thoughts? These questions represent, to all likelihood, the most challenging matters ever faced by natural sciences, matters which may never be fully comprehended. The evolution of the nervous system that, in about billion of years, brought into existence the human brain progressed through an ever-increasing complexity of neural networks. This evolution began from the diffuse nervous system, in which primordial neurons were able to sense the environmental inputs and convey them to effector organs and to the neighbouring neurons. At the next evolutionary stage the conglomerates of neuronal cell bodies, the ganglia, appeared, thus forming the primitive centralized nervous system. The developments which ensued went through a continuous increase in complexity of neuronal conglomerates, which eventually formed the central nervous system, which attained maximal perfection in mammals. In this issue of ASN NEURO, Osborne et al. have described details of real-time imaging of cannabinoid receptor trafficking in astrocytes, a technique that will help to elucidate the role of these receptors in the ever-increasing complex neural networks

Inclusive Brain: From Neuronal Doctrine to the Active Milieu

This work was supported by the Russian Foundation for Basic Research (RFBR), Grant No. 21-54-53018

Lifestyle-dependent microglial plasticity: training the brain guardians

Lifestyle is one of the most powerful instruments shaping mankind; the lifestyle includes many aspects of interactions with the environment, from nourishment and education to physical activity and quality of sleep. All these factors taken in complex affect neuroplasticity and define brain performance and cognitive longevity. In particular, physical exercise, exposure to enriched environment and dieting act through complex modifications of microglial cells, which change their phenotype and modulate their functional activity thus translating lifestyle events into remodelling of brain homoeostasis and reshaping neural networks ultimately enhancing neuroprotection and cognitive longevity

Lifestyle-dependent microglial plasticity: training the brain guardians.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-08-01, epub 2021-08-05Publication status: PublishedLifestyle is one of the most powerful instruments shaping mankind; the lifestyle includes many aspects of interactions with the environment, from nourishment and education to physical activity and quality of sleep. All these factors taken in complex affect neuroplasticity and define brain performance and cognitive longevity. In particular, physical exercise, exposure to enriched environment and dieting act through complex modifications of microglial cells, which change their phenotype and modulate their functional activity thus translating lifestyle events into remodelling of brain homoeostasis and reshaping neural networks ultimately enhancing neuroprotection and cognitive longevity

Memory formation shaped by astroglia

Astrocytes, the most heterogeneous glial cells in the central nervous system (CNS), execute a multitude of homeostatic functions and contribute to memory formation. Consolidation of synaptic and systemic memory is a prolonged process and hours are required to form long-term memory. In the past, neurons or their parts have been considered to be the exclusive cellular sites of these processes, however, it has now become evident that astrocytes provide an important and essential contribution to memory formation. Astrocytes participate in the morphological remodeling associated with synaptic plasticity, an energy-demanding process that requires mobilization of glycogen, which, in the CNS, is almost exclusively stored in astrocytes. Synaptic remodeling also involves bidirectional astroglial-neuronal communication supported by astroglial receptors and release of gliosignaling molecules. Astroglia exhibit cytoplasmic excitability that engages second messengers, such as Ca(2+), for phasic, and cyclic adenosine monophosphate (cAMP), for tonic signal coordination with neuronal processes. The detection of signals by astrocytes and the release of gliosignaling molecules, in particular by vesicle-based mechanisms, occurs with a significant delay after stimulation, orders of magnitude longer than that present in stimulus–secretion coupling in neurons. These particular arrangements position astrocytes as integrators ideally tuned to support time-dependent memory formation

Astroglial networks in health and disease: New Frontiers

The common and prevailing point of view considers neurones as main substrates of pathological progression of neurological diseases. Today, however, we know that integration and information processing in the brain occurs though close interactions of two cellular circuits represented by neuronal networks embedded into internally connected astroglial syncytia. Our understanding of glial function changed dramati- cally over last two decades. This change concerns the whole concept of how the brain is organized, and how the development, life and death of neural circuits are controlled. There is compelling evidence demonstrating that these are the astrocytes that are creating the compartmentalisation in the CNS, and these are the astrocytes that are able to integrate neurones, synapses, and brain capillaries into individual and relatively independent units. Astroglial syncytia allow intercellular communica- tion routes, which permit translocation of ions, metabolic factors and second messen- gers. The resulting potential for parallel processing and integration is significant and might easily be larger, but also fuzzier, than the binary coded electrical communica- tion within the neuronal networks. The neuronal-glial circuitry endowed with distinct signalling cascades, form a “diffuse nervous net” suggested by Golgi, where millions of synapses belonging to very different neurones are integrated first into neuronal- glial-vascular units and then into more complex structures connected through glial syncytia. These many levels of integration, both morphological and functional, pre- sented by neuronal-glial circuitry ensure the spatial and temporal multiplication of brain cognitive power.Neuroglial cells are intimately involved in all forms of neurological diseases and this are neuroglia, which, to a very large extent, determine the progression and outcome of neuropathological process. Astrocytes are specifically involved in vari- ous neurodegenerative diseases including Alzheimer’s disease, Amyotrophic lateral sclerosis, Parkinson’s disease and various forms of dementia. Recent evidence sug- gest that early stages of neurodegenerative processes are associated with atrophy of astroglia, which causes disruptions in synaptic connectivity, disbalance in neurotrans- mitter homeostasis and neuronal death through increased excitotoxicity. At the later stages astrocytes became activated and contribute to neuro-inflammatory component of neurodegeneration.

Glial decline and loss of homeostatic support rather than inflammation defines cognitive aging

The work of AS was supported by the Russian Science Foundation, No. 20-14-00241

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