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Astrocyte syncytium:from neonatal genesis to aging degeneration

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Neural Regeneration Research 2024年第2期19卷 395-396页

作者： Min Zhou Shiying Zhong Alexei Verkhratsky Department of neuroscience Ohio State University Wexner Medical CenterColumbusOHUSA Faculty of Biology Medicine and HealthThe University of ManchesterManchesterUK Achücarro basque center for neuroscience IKERBASQUEBasque Foundation for ScienceBilbaoSpain Department of neurosciences University of the Basque Country UPV/EHU and CIBERNEDLeioaSpain

Modern neuroscience began from all reaching and fierce conflict between“neuronismo and reticulismo”——between neuronal and reticular theories of the organization of the nervous system;the conflict culminated in December of 1906 in Stockholm where Santiago Ramon y Cajal(the proponent of the neuronal doctrine)and Camillo Golgi(who advocated the syncytial reticular organization of neural networks)delivered their Noble prize lectures(Verkhratsky,2009).

关键词： degeneration neonatal aging

Astrocytes dynamically regulate the blood-brain barrier in the healthy brain

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Neural Regeneration Research 2024年第4期19卷 709-710页

作者： AgnėPociūtė Augustas Pivoriūnas Alexei Verkhratsky Department of Stem Cell Biology State Research Institute Centre for Innovative MedicineVilniusLithuania Faculty of Biology Medicine and HealthThe University of ManchesterManchesterUK achucarro Centre for neuroscience IKERBASQUEBasque Foundation for ScienceBilbaoSpain Department of Forensic Analytical Toxicology School of Forensic MedicineChina Medical UniversityShenyangLiaoning ProvinceChina

The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervous system from the circulation is evolutionarily conserved from arthropods to man.The primeval BBB of the invertebrates and some early vertebrates was made solely by glial cells and secured(in invertebrates)by septate junctions.

关键词： Ehrlich barrier blood

Alterations of protein homeostasis in Alzheimer's disease:beyond Procrustean bed of endoplasmic reticulum stress and unfolded protein response

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Neural Regeneration Research 2024年第8期19卷 1645-1646页

作者： Dmitry Lim Alexei Verkhratsky Department of Pharmaceutical Sciences Universitàdel Piemonte Orientale“Amedeo Avogadro”NovaraItaly Faculty of Biology Medicine and HealthThe University of ManchesterManchesterUK achucarro center for neuroscience IKERBASQUEBasque Foundation for ScienceBilbaoSpain&Department of NeurosciencesUniversity of the Basque Country UPV/EHU and CIBERNEDLeioaSpain Department of Stem Cell Biology State Research Institute Centre for Innovative MedicineVilniusLithuania Department of Forensic Analytical Toxicology School of Forensic MedicineChina Medical UniversityShenyangLiaoning ProvinceChina

Alzheimer’s disease(AD)is a major age-related form of dementia with a number of cases exponentially growing,causing enormous social and economic impact on individuals and society.Neuropathological hallmarks of AD,evident in postmortem AD brains,include a massive loss of the grey matter in the neocortex,extracellular deposition of amyloid-β(Aβ)in the form of senile plaques and cerebrovascular amyloid angiopathy,and intra-neuronal accumulation of neurofibrillary tangles,formed by hyper-phosphorylated tau protein.

关键词： Alzheimer homeostasis cortex

Astrocyte chloride,excitatory-inhibitory balance and epilepsy

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Neural Regeneration Research 2024年第9期19卷 1887-1887页

作者： Verena Untiet Maiken Nedergaard Alexei Verkhratsky Division of Glial Disease and Therapeutics Center for Translational NeuromedicineUniversity of CopenhagenCopenhagenDenmark Division of Glial Disease and Therapeutics Center for Translational NeuromedicineDepartment of NeurosurgeryUniversity of Rochester Medical CenterRochesterNYUSA Faculty of Biology Medicine and HealthThe University of ManchesterManchesterUK achucarro Centre for neuroscience IKERBASQUEBasque Foundation for ScienceBilbaoSpain

Excitation and inhibition are at the core of brain function and malfunction.To sustain the activity of neuronal networks over time and space,glutamatergic excitation is balanced by GABAergic inhibition.The equipoise of excitation and inhibition,known as the excitation/inhibition(E/I)balance,is crucial for proper brain function.The E/I balance is highly dynamic and shifts across different brain states:wakefulness primarily augments excitatory activity,while sleep promotes a decrease in excitation and an increase in inhibition(Bridi et al.,2020).Neuronal activity during various brain states is primarily regulated by neurotransmitters(Schiemann et al.,2015),alongside non-synaptic mechanisms that operate on a slower timescale.The non-synaptic mechanisms are many,with the ionic composition of the extracellular space playing a significant role;altering extracellular ion concentrations affects sleep,arousal,electroencephalogram patterns,and behavioral states(Ding et al.,2016).

关键词： epilepsy excitatory excitation

Clearing the corpses： regulatory mechanisms, novel tools, and therapeutic potential of harnessing microglial phagocytosis in the diseased brain

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Neural Regeneration Research 2016年第10期11卷 1533-1539页

作者： Irune Diaz-Aparicio Sol Beccari Oihane Abiega Amanda Sierra achucarro basque center for neuroscience Bizkaia Science and Technology Park Zamudio Spain University of the basque Country Leioa Spain Ikerbasque Foundation Bilbao Spain

Apoptosis is a widespread phenomenon that occurs in the brain in both physiological and pathological conditions. Dead ceils must be quickly removed to avoid the further toxic effects they exert in the pa- renchyma, a process executed by microglia, the brain professional phagocytes. Although phagocytosis is critical to maintain tissue homeostasis, it has long been either overlooked or indirectly assessed based on microglial morphology, expression of classical activation markers, or engulfment of artificial phagocytic targets in vitro. Nevertheless, these indirect methods present several limitations and, thus, direct obser- vation and quantification of microglial phagocytosis is still necessary to fully grasp its relevance in the diseased brain. To overcome these caveats and obtain a comprehensive, quantitative picture of microglial phagocytosis we have developed a novel set of parameters. These parameters have allowed us to identify the different strategies utilized by microglia to cope with apoptotic challenges induced by excitotoxicity or inflammation. In contrast, we discovered that in mouse and human epilepsy microglia failed to find and engulf apoptotic ceils, resulting in accumulation of debris and inflammation. Herein, we advocate that the efficiency of microglial phagocytosis should be routinely tested in neurodegenerative and neuro- logical disorders, in order to determine the extent to which it contributes to apoptosis and inflammation found in these conditions. Finally, our findings point towards enhancing microglial phagocytosis as a novel therapeutic strategy to control tissue damage and inflammation, and accelerate recovery in brain diseases.

关键词： microglia phagocytosis apoptosis impairment epilepsy brain diseases neurodegeneration inflammation neuroinflammation

Evaluation of glial cell proliferation with non-invasive molecular imaging methods after stroke

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Neural Regeneration Research 2021年第11期16卷 2209-2210页

作者： Ana Joya Abraham Martín achucarro basque center for neuroscience LeioaSpain CIC biomaGUNE Basque Research and Technology Alliance(BRTA)PaseoSpain Ikerbasque basque Foundation for Science BilbaoSpain

Glial proliferation:For the last decades,glial cells have been wrongly believed to have a mere passive supporting role for neurons.Nevertheless,this notion has clearly changed and it is now admitted that these cells are essential for the correct development and regulation of the nervous system.Glia cell population are commonly subdivided in astrocytes,oligodendrocytes and microglia.During the development,neural stem cells(NSCs)(called neuroepithelial progenitor cells or NPCs)transform into radial glia,the primary progenitor cells for neurons,astrocytes and oligodendrocytes(Zuchero and Barres,2015).Microglial cells,however,derive from a mesenchymal precursor infiltration,meaning that during brain development,precursors generated in the bone narrow invade the nervous parenchyma and differentiate into microglial cells(Zuchero and Barres,2015).This proliferative capacity is preserved in the adult mammalian brain,and neurogenic NSCs are stored in two restricted regions of the central nervous system(CNS),the forebrain subventricular zone(SVZ)and the hippocampal dentate gyrus(subgranular zone).These cells continue to produce neurons and glial cells during the adulthood,being activated after certain signals and leaving the quiescent state(Urbán et al.,2019).This process,in which glial progenitor cells differentiate into mature glia during development and in the adult brain to maintain and regulate brain function,is called gliogenesis(Ardaya et al.,2020).

关键词： admitted maintain supporting

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

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Neural Regeneration Research 2022年第3期17卷 565-566页

作者： Alexei Verkhratsky Natalia Lazareva Alexey Semyanov Faculty of Biology Medicine and HealthThe University of ManchesterManchesterUK achucarro center for neuroscience IKERBASQUEBasque Foundation for ScienceBilbaoDepartment of NeurosciencesUniversity of the Basque Country UPV/EHU and CIBERNEDLeioaSpain Sechenov First Moscow State Medical University MoscowRussia Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of SciencesFaculty of BiologyMoscow State UniversityMoscowRussia

The preservation of cognitive longevity and arresting the pandemic of senile dementia engulfing the modern world is arguably the major challenge faced by biomedical research in the 21st century.Age is the leading risk factor for neurodegenerative diseases and vascular dementia,and yet there is a clear distinction between physiological and pathological brain aging.

关键词： inflammation senile aging

Store-operated calcium entry in neuroglia

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neuroscience Bulletin 2014年第1期30卷 125-133页

作者： Alexei Verkhratsky Vladimir Parpura Faculty of Life Sciences The University of Manchester achucarro center for neuroscience IKERBASQUE Basque Foundation for Science 48011 Bilbao Spain and Department of neurosciences University of the Basque Country UPV/EHU Department of Neurobiology Center for Glial Biology in Medicine Atomic Force Microscopy & Nanotechnology aboratories Civitan International Research Center Evelyn F. McKnight Brain Institute University of Alabama Department of Biotechnology University or Rijeka

Neuroglial cells are homeostatic neural cells. Generally, they are electrically non-excitable and their activation is associated with the generation of complex intracellular Ca^2＋ signals that define the ＂Ca^2＋ excitability＂ of glia. In mammalian glial cells the major source of Ca^2＋ for this excitability is the lumen of the endoplasmic reticulum （ER）, which is ultimately （re）filled from the extracellular space. This occurs via store-operated Ca^2＋ entry （SOCE） which is supported by a specific signaling system connecting the ER with plasmalemmal Ca^2＋ entry. Here, emptying of the ER Ca^2＋ store is necessary and sufficient for the activation of SOCE, and without Ca^2＋ influx via SOCE the ER store cannot be refilled. The molecular arrangements underlying SOCE are relatively complex and include plasmalemmal channels, ER Ca^2＋ sensors, such as stromal interaction molecule, and possibly ER Ca^2＋ pumps （of the SERCA type）. There are at least two sets of plasmalemmal channels mediating SOCE, the Ca2＊-release activated channels, Orai, and transient receptor potential （TRP） channels. The molecular identity of neuroglial SOCE has not been yet identified unequivocally. However, it seems that Orai is predominantly expressed in microglia, whereas astrocytes and oligodendrocytes rely more on TRP channels to produce SOCE. In physiological conditions the SOCE pathway is instrumental for the sustained phase of the Ca^2＋ signal observed following stimulation of metabotropic receptors on glial cells.

关键词： calcium signaling astrocyte oligodendrocyte microglia store-operated calcium entry TRP STIM Orai

Neural activation while perceiving biological motion in dynamic facial expressions and point-light body action animations

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Neural Regeneration Research 2010年第14期5卷 1076-1083页

作者： Lorna García Pentón Alejandro Pérez Fernández María A.Bobes León Yanely Acosta Ymas Lídice Galán García Yasser Iturria-Medina Sandra E.Leh Mitchell Valdés-Sosa Cognitive neuroscience Laboratory Faculty of PsychologyUniversidad Diego Portales basque center on Cognition Brain and Language Cognitive Department Cuban Neuroscience Center Neuroimaging Department Cuban Neuroscience Center Montreal Neurological Institute & Hospital

BACKGROUND： The interpretation of non-verbal social signals relies heavily on the ability to perceive biological motion. The posterior superior temporal sulcus is an important part of a network involved in biological motion processing. However, the underlying functional organization remains poorly understood. Several studies have suggested topographical representation of motion from different body parts within this region. However, other studies have shown that the posterior superior temporal sulcus responds equally to any body part. OBJECTIVE： Through the use of functional magnetic resonance imaging, the effects of socially relevant biological motion stimuli to activate a specific cortical area within posterior superior temporal sulcus, even if different body parts are involved in motion, will be analyzed. DESIGN, TIME AND SETTING： A functional magnetic resonance imaging, block-design was performed at the Magnetic Resonance Imaging, Surgical Medical Investigation center, Havana, Cuba between 2004 and 2005. PARTICIPANTS： Thirteen healthy volunteers, from 19 to 55 years of age and compris!ng eight males and five females, were included in the study. METHODS： A conjunction analysis of responses to natural, dynamic, fearful, facial expressions and point-light, body-motion animations. MAIN OUTCOME MEASURES： The corresponding functionally specialized areas, as well as neural areas significant for both types of stimuli, were identified. RESULTS： One region within the posterior superior temporal sulcus of the right hemisphere was equally activated by facial and body complex motion. CONCLUSION： A site of common neural activity existed within the posterior superior temporal sulcus, which was not specific to a biological motion type. In addition, the activity was not related to a topographically organized body-part map, which suggested high-level visual representation of biological motion in this region.

关键词： human movement body movement dynamic faces emotional expressions common neural activation overlapped activations