Alexei Verkhratsky

The University of Manchester · Faculty of Life Sciences

Astroglial perisynaptic sheath covers the majority of synapses in the central nervous system. This glial coverage evolved as a part of the synaptic structure in which elements directly responsible for neurotransmission (exocytotic machinery and appropriate receptors) concentrate in neuronal membranes, whereas multiple molecules imperative for homeo...

Neuroglia are represented by several population of cells heterogeneous in structure and function that provide for the homeostasis of the brain and the spinal cord. Neuroglial cells are also central for neuroprotection and defence of the central nervous system against exo- and endogenous insults. At the early stages of neurodegenerative diseases inc...

The entorhinal-hippocampal circuit is severely affected in Alzheimer's disease (AD). Here, we demonstrate that amyloid-β (Aβ) differentially affects primary cultured astrocytes derived from the entorhinal cortex (EC) and from the hippocampus from non-transgenic controls and 3xTg-AD transgenic mice. Exposure to 100 nM of Aβ resulted in increased exp...

The peripheral nervous system (PNS) consists of the nerves and ganglia outside of the brain and spinal cord. There are four major types of glia in the PNS. They are myelinating and non-myelinating Schwann cells, satellite glial cells (SGCs), enteric glial cells (EGCs), and olfactory ensheathing cells (OECs). Schwann cells support regeneration and s...

Astroglial excitability is largely mediated by fluctuations in intracellular ion concentrations. In addition to generally acknowledged Ca²⁺ excitability of astroglia, recent studies have demonstrated that neuronal activity triggers transient increases in the cytosolic Na⁺ concentration ([Na⁺](i)) in perisynaptic astrocytes. These [Na⁺](i) transient...

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...

Inflammatory pain, sustained by a complex network of inflammatory mediators, is a severe and persistent illness affecting many of the general population. We explore possible anti-inflammatory pathways of Polyphyllin VI (PPVI) based on our prior study, which showed that PPVI reduces inflammation in mice to reduce pain. Network pharmacology and RNA-S...

Background and objective: Itch, an unpleasant sensation prompting the urge to scratch, and pain, aimed at detecting potential harm through acute withdrawal or protective behaviors, are increasingly recognized as interconnected phenomena. The co-occurrence of itch and pain symptoms in various diseases impairs therapeutic efficacy and the quality of...

Mechanisms controlling movement of the CSF through the central canal towards the peripheral nerves are poorly characterized. We found that fluorescent dyes injected into cisterna magna are carried with cerebrospinal fluid (CSF) through the central canal and peripheral nerves to the peripheral organs such as liver, and pancreas. We also found close...

Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence of the central nervous system (CNS). Astroglia contribute to the pathophysiology of all neurological and neuropsychiatric disorders in ways that can be either beneficial or detrimental to disorder outcome. Pathophysiological changes in astroglia...

Ke y w ords: scientific errors; correction of errors; fraud; irreproducibility; wrong methodology The famous phrase "Errar e human um est, sed in errare perse-v erar e dia bolicum" ("To err is human, but to persist in error is diabolical"), which is attributed to the Roman philosopher and orator Lucius Annaeus Seneca (∼4 bce to 65 ce), is as r elev...

The immunomodulatory cellular network that triggers early inflammation and demyelination, the key steps in multiple sclerosis (MS) pathogenesis remains poorly characterized. Here, we demonstrate that overactivation of Wnt pathway promotes pathological transformation of oligodendrocyte precursor cells (OPCs) to replicate pathological OPCs in human M...

The pandemic of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) instigated the most serious global health crisis. Clinical presentation of COVID-19 frequently includes severe neurological and neuropsychiatric symptoms. However, it is presently unknown whether and to which extent pathologica...

Neuronal morphogenesis relies on intercellular signaling. Astrocytes release metabolites, trophic, and guidance factors to promote neuronal differentiation. In contrast, the mechanisms by which astrocytes could limit and stabilize neuronal connectivity remain less explored. Here, we show cortical astrocytes to express and release S100A6, a Ca2+-bin...

Inflammatory pain, sustained by a complex network of inflammatory mediators, is a severe and persistent illness affecting a large proportion of the general population. Based on our earlier research showing that Polyphyllin VI (PPVI) alleviates pain by reducing inflammation in mice we proceed to identify potential anti-inflammatory mechanisms of PPV...

Astrocyte atrophy is the main histopathological hallmark of major depressive disorder (MDD) in humans and in animal models of depression. Here we show that electroacupuncture prevents astrocyte atrophy in the prefrontal cortex and alleviates depressive-like behaviour in mice subjected to chronic unpredictable mild stress (CUMS). Treatment of mice w...

Nervous system pathophysiology is poorly understood. This translates into limited therapeutic options for neurological diseases, ranging from neurodegenerative diseases to neuropsychiatric disorders. The deficits in our knowledge reflect the complexity of the human brain, which is certainly the most complex system that confronts the natural science...

Adult oligodendrocyte precursor cells (aOPCs), transformed from fetal OPCs, are idiosyncratic neuroglia of the central nervous system (CNS) that are distinct in many ways from other glial cells. OPCs have been classically studied in the context of their remyelinating capacity. Recent studies, however, revealed that aOPCs not only contribute to post...

Lia et al. [1] discovered the critical role of STIM1 ER Ca2+ sensor in the functional decline of astrocytes in the AD-like pathology in PS2APP mice. Profound downregulation of STIM1 expression in astrocytes in the disease results in the decreased ER Ca2+ content and severely impaired evoked as well as spontaneous astrocytic Ca2+ signalling. Aberran...

Ageing is associated with a morphological and functional decline of astrocytes with a prevalence of morphological atrophy and loss of function. In particular, ageing is manifested by the shrinkage of astrocytic processes: branches and leaflets, which decreases synaptic coverage. Astrocytic dystrophy affects multiple functions astrocytes play in the...

Locomotion triggers a coordinated response of both neurons and astrocytes in the brain. Here we performed calcium (Ca2+) imaging of these two cell types in the somatosensory cortex in head-fixed mice moving on the airlifted platform. Ca2+ activity in astrocytes significantly increased during locomotion from a low quiescence level. Ca2+ signals firs...

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiolo...

Textbook of neuroglia covering all aspects of glial physiology and pathophysiology.

Information transfer within neuronal circuits depends on the balance and recurrent activity of excitatory and inhibitory neurotransmission. Chloride (Cl⁻) is the major central nervous system (CNS) anion mediating inhibitory neurotransmission. Astrocytes are key homoeostatic glial cells populating the CNS, although the role of these cells in regulat...

Neuropathological mechanisms of manic syndrome or manic episodes in bipolar disorder remain poorly characterised, as the research progress is severely limited by the paucity of appropriate animal models. Here we developed a novel mania mice model by combining a series of chronic unpredictable rhythm disturbances (CURD), which include disruption of...

Adult neurogenesis is a striking example of neuroplasticity, which enables adaptive network remodelling in response to all forms of environmental stimulation in physiological and pathological contexts. Dysregulation or cessation of adult neurogenesis contributes to neuropathology negatively affecting brain functions and hampering regeneration of th...

Astrocytes contribute to the progression of neurodegenerative diseases, including Alzheimer's disease (AD). Here, we report the neuroanatomical and morphometric analysis of astrocytes in the entorhinal cortex (EC) of the aged wild type (WT) and triple transgenic (3xTg-AD) mouse model of AD. Using 3D confocal microscopy, we determined the surface ar...

Protein misfolding is prominent in early cellular pathology of Alzheimer's disease (AD), implicating pathophysiological significance of endoplasmic reticulum stress/unfolded protein response (ER stress/UPR) and highlighting it as a target for drug development. Experimental data from animal AD models and observations on human specimens are, however,...

Astrocyte atrophy is the main histopathological hallmark of the major depressive disorder (MDD) in humans and in animal models of depression. Here we show that electroacupuncture prevents astrocyte atrophy in the prefrontal cortex and alleviates depressive-like behaviour in mice subjected to the chronic unpredictable mild stress (CUMS). Treatment o...

Astrocytes display a highly complex, spongiform morphology, with their fine terminal processes (leaflets) exercising dynamic degrees of synaptic coverage, from touching and surrounding the synapse to being retracted from the synaptic region. In this paper, a computational model is used to reveal the effect of the astrocyte-synapse spatial relations...

Astrocyte atrophy is the main histopathological hallmark of the major depressive disorder (MDD) in humans and in animal models of depression. Here we show that electroacupuncture prevents astrocyte atrophy in the prefrontal cortex and alleviates depressive-like behaviour in mice subjected to the chronic unpredictable mild stress (CUMS). Treatment o...

Objective: Inflammatory pain is one of the most common diseases in daily life and clinic. In this work, we analysed bioactive components of the traditional Chinese medicine Chonglou and studied mechanisms of their analgesic effects. Material and methods: Molecular docking technology and U373 cells overexpressing P2X3 receptors combined with the cel...

Nervous system is segregated from the body by the complex system of barriers. The CNS is protected by (i) the blood-brain and blood-spinal cord barrier between the intracerebral and intraspinal blood vessels and the brain parenchyma; (ii) the arachnoid blood-cerebrospinal fluid barrier; (iii) the blood-cerebrospinal barrier of circumventricular org...

Key homeostasis providing cells in the central nervous system (CNS) are astrocytes, which belong to the class of cells known as atroglia, a highly heterogeneous type of neuroglia and a prominent element of the brain defence. Diseases evolve due to altered homeostatic state, associated with pathology-induced astroglia remodelling represented by reac...

Astrocytes are key homeostatic and defensive cells of the central nervous system (CNS). They undertake numerous functions during development and in adulthood to support and protect the brain through finely regulated communication with other cellular elements of the nervous tissue. In Alzheimer's disease (AD), astrocytes undergo heterogeneous morpho...

Oligodendrocyte precursor cells (OPCs) undergo an extensive and coordinated migration in the developing CNS, using the pre-formed scaffold of developed blood vessels as their physical substrate for migration. While OPC association with vasculature is critical for dispersal, equally important for permitting differentiation and proper myelination of...

How aging affects cellular components of the human brain active milieu remains largely unknown. We analyzed astrocytes and neurons in the neocortical access tissue of younger (22-50 years) and older (51-72 years) adult patients who underwent glioma resection. Aging decreased the amount of reduced mitochondrial cytochromes in astrocytes but not neur...

Microglial research has advanced considerably in recent decades yet has been constrained by a rolling series of dichotomies such as “resting versus activated” and “M1 versus M2.” This dualistic classification of good or bad microglia is inconsistent with the wide repertoire of microglial states and functions in development, plasticity, aging, and d...

In the human brain glial cells are as abundant as neurons. The relative number of glial cells has increased with increasing complexity of the central nervous system (CNS) during evolution. In vertebrates three types of glial cells can be distinguished in the CNS, namely, astrocytes, oligodendrocytes, and microglia. In the peripheral nervous system...

The evolution of the nervous system progressed through cellular diversification and specialization of functions. Conceptually, the nervous system is composed of electrically excitable neuronal networks connected by chemical synapses and nonexcitable glial cells that provide for homeostasis and defense. The evolution of neuroglia began with the emer...

Astrocytes display a highly complex, spongiform morphology, with their fine terminal processes (leaflets) exercising dynamic degrees of synaptic coverage, from touching and surrounding the synapse to being retracted from the synaptic region. In this paper, a computational model is used to reveal the effect of the astrocyte-synapse spatial relations...

Although the link of white matter to pathophysiology of schizophrenia is documented, loss of myelin is not detected in patients at the early stages of the disease, suggesting that pathological evolution of schizophrenia may occur before significant myelin loss. Disrupted-in-schizophrenia-1 (DISC1) protein is highly expressed in oligodendrocyte prec...

Major depressive disorder (MDD) is one of the most prevalent psychiatric illnesses worldwide which impairs the social functioning of the afflicted patients. Astrocytes promote homeostasis of the CNS and provide defense against various types of harmful influences. Increasing evidence suggests that the number, morphology and function of astrocytes ar...

The treatment of chronic itch is considered to be a challenge for its non-histamine dependence and the search for alternative medicine is still striving. The pathology of the chronic itch is closely related to immune system regulation and inflammatory response. Oxymatrine (OMT) is a traditional Chinese medicine ingredient extracted from the roots o...

Multiple paracrine factors are implicated in the regulation of barrier properties of human brain endothelial cells (BECs) in different physiologic and pathologic settings. We have recently demonstrated that autocrine secretion of basic fibroblast growth factor (bFGF) by BECs is necessary for the establishment of endothelial barrier (as demonstrated...

Alzheimer’s disease (AD) is a neurodegenerative disorder that causes age-dependent neurological and cognitive declines. The treatments for AD pose a significant challenge, because the mechanisms of disease are not being fully understood. Malfunction of the blood-brain barrier (BBB) is increasingly recognized as a major contributor to the pathophysi...

Multiple paracrine factors have been implicated in the regulation of barrier properties of human brain endothelial cells (BECs) in different physiologic and pathologic settings. We have recently demonstrated that autocrine secretion of basic broblast growth factor (bFGF) by BECs is necessary for the establishment of endothelial barrier (as demonstr...

Astrocytes contribute to the complex cellular pathology of Alzheimer’s disease (AD). Neurons and astrocytes function in close collaboration through neurotransmitter recycling, collectively known as the glutamate/GABA-glutamine cycle, which is essential to sustain neurotransmission. Neurotransmitter recycling is intimately linked to astrocyte energy...

Accumulating evidence suggests that the activation of nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome contributes to the pathophysiology of post-traumatic stress disorder (PTSD). Astrocytes, the homeostatic cells of the central nervous system are intimately involved into pathophysiology of various mental disorders i...

Aim: A high-fat diet (HFD) is generally considered to negatively influence the body, the brain, and cognition. Nonetheless, fat and fatty acids are essential for nourishing and constructing brain tissue. Astrocytes are central for lipolysis and fatty acids metabolism. We tested how HFD affects astrocyte metabolism, morphology and physiology. Meth...

Alzheimer’s disease (AD) is the prevalent cause of dementia in the ageing world population. Apolipoprotein E4 (ApoE4) allele is the key genetic risk factor for AD, although the mechanisms linking ApoE4 with neurocognitive impairments and aberrant metabolism remains to be fully characterised. We discovered a significant increase in the ApoE4 content...

Although posttraumatic stress disorder (PTSD) is on the rise, traumatic events and their consequences are often hidden or minimized by patients for reasons linked to PTSD itself. Traumatic experiences can be broadly classified into mental stress (MS) and traumatic brain injury (TBI), but the cellular mechanisms of MS-or TBI-induced PTSD remain unkn...

Although the link of white matter to pathophysiology of schizophrenia is documented, loss of myelin is not detected in patients at the early stages of the disease, suggesting that pathological evolution of schizophrenia may occur before significant myelin loss. Disrupted-in-schizophrenia-1 (DISC1) protein is highly expressed in oligodendrocyte prec...

Neuropathological mechanisms triggering manic syndrome or manic episodes in bipolar disorder remain poorly characterised, as the research progress is severely limited by the paucity of appropriate animal models. Here we developed a novel manic mice model by combining a series of chronic unpredictable rhythm disturbances (CURD), which include disrup...

The brain active milieu. The brain as an organ is organised from several interconnected structures: neocortex, hippocampus, thalamus, cerebellum and so on. Each structure is built of multiple cell types (including neurons, neuroglia and non-neural cells) and non-cellular elements (extracellular space with extracellular matrix). All these elements a...

Information transfer within neuronal circuits depends on the balance and recurrent activity of excitatory and inhibitory neurotransmission. Chloride (Cl ⁻ ) is the major CNS anion mediating inhibitory neurotransmission and thus essential for balanced brain function. Sustained activation of inhibitory synapses leads to a significant reduction in the...

Extracellular adenosine 5′-triphosphate (ATP) in the brain is suggested to be an etiological factor of major depressive disorder (MDD). It has been assumed that stress-released ATP stimulates P2X7 receptors (Rs) at the microglia, thereby causing neuroinflammation; however, other central nervous system (CNS) cell types such as astrocytes also posses...

Stroke causes degeneration and death of neurones leading to the loss of motor function and frequent occurrence of cognitive impairment and depression. Lithium (Li⁺), the archetypal mood stabiliser, is neuroprotective in animal models of stroke, albeit underlying mechanisms remain unknown. We discover that Li⁺ inhibits activation of nucleotide-bindi...

Major depressive disorder (MDD) presents multiple clinical phenotypes and has complex underlying pathological mechanisms. Existing theories cannot completely explain the pathophysiological mechanism(s) of MDD, while the pharmacology of current antidepressants is far from being fully understood. Astrocytes, the homeostatic and defensive cells of the...