Homeostatic function of astrocytes: Ca2+ and Na+ signalling

Parpura, Vladimir; Verkhratsky, Alexei

doi:10.2478/s13380-012-0040-y

Cited by 111 publications

(75 citation statements)

References 142 publications

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“…Astroglial expression of a wide array of receptors for neurotransmitters and neurohormones is regulated by the neurochemical environment and, as a rule, astrocytes possess receptors allowing them to sense neighboring neuronal transmission (Parpura and Verkhratsky, 2012a). Activation of these receptors triggers dynamic changes of concentration of ions (mainly Ca 2+ and Na + ) in the astroglial cytoplasm, which regulate astroglial functions and serve as a substrate for astroglial excitability (Agulhon et al ., 2008; Kirischuk et al ., 2012; Parpura and Verkhratsky, 2012b, 2013; Rose and Karus, 2013; Verkhratsky et al ., 2014c; Zorec et al ., 2012). The functions of astrocytes are highly diverse and are regionally specialized (Anderson et al ., 2014; Chaboub and Deneen, 2012; Matyash and Kettenmann, 2010; Oberheim et al ., 2012; Parpura et al ., 2012; Schitine et al ., 2015).…”

Section: Astrogliopathology: Reactivity Atrophy With Loss Of Funcmentioning

confidence: 99%

Translational potential of astrocytes in brain disorders

Verkhratsky

Steardo²,

Parpura

et al. 2016

Progress in Neurobiology

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Fundamentally, all brain disorders can be broadly defined as the homeostatic failure of this organ. As the brain is composed of many different cells types, including but not limited to neurons and glia, it is only logical that all the cell types/constituents could play a role in health and disease. Yet, for a long time the sole conceptualization of brain pathology was focused on the well-being of neurons. Here, we challenge this neuron-centric view and present neuroglia as a key element in neuropathology, a process that has a toll on astrocytes, which undergo complex morpho-functional changes that can in turn affect the course of the disorder. Such changes can be grossly identified as reactivity, atrophy with loss of function and pathological remodeling. We outline the pathogenic potential of astrocytes in variety of disorders, ranging from neurotrauma, infection, toxic damage, stroke, epilepsy, neurodevelopmental, neurodegenerative and psychiatric disorders, Alexander disease to neoplastic changes seen in gliomas. We hope that in near future we would witness glial-based translational medicine with generation of deliverables for the containment and cure of disorders. We point out that such as a task will require a holistic and multi-disciplinary approach that will take in consideration the concerted operation of all the cell types in the brain.

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Section: Astrogliopathology: Reactivity Atrophy With Loss Of Funcmentioning

confidence: 99%

Translational potential of astrocytes in brain disorders

Verkhratsky

Steardo²,

Parpura

et al. 2016

Progress in Neurobiology

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“…The role for sodium signalling in astroglial excitability has been considered rather recently [54][55][56][57]. It appeared that stimulation of astrocytes with neurotransmitters released from neuronal terminals triggers long lasting elevation of cytosolic Na + ([Na + ] i ) with amplitudes of 5 -20 mM [58][59][60][61]; this [Na + ] i increase resulted from Na + entry through plasmalemmal channels (mainly ionotropic receptors) and transporters (mainly Na + -dependent glutamate transporters).…”

Section: Ionic Excitability Of Astrogliamentioning

confidence: 99%

Astroglial calcium signalling in Alzheimer's disease

Verkhratsky

Rodriguez-Arellano

Parpura

et al. 2017

Biochemical and Biophysical Research Communications

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Neuroglial contribution to Alzheimer's disease (AD) is pathologically relevant and highly heterogeneous. Reactive astrogliosis and activation of microglia contribute to neuroinflammation, whereas astroglial and oligodendroglial atrophy affect synaptic transmission and underlie the overall disruption of the central nervous system (CNS) connectome. Astroglial function is tightly integrated with the intracellular ionic signalling mediated by complex dynamics of cytosolic concentrations of free Ca 2+ and Na + . Astroglial ionic signalling is mediated by plasmalemmal ion channels, mainly associated with ionotropic receptors, pumps and solute carrier transporters, and by intracellular organelles comprised of the endoplasmic reticulum and mitochondria. The relative contribution of these molecular cascades/organelles can be plastically remodelled in development and under environmental stress. In AD astroglial Ca 2+ signalling undergoes substantial reorganisation due to an abnormal regulation of expression of Ca 2+ handling molecular cascades.

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“…These inflammatory mediators play a regulatory role in the growth, differentiation, and activation of immune cells [49]. Glial cells (microglia, astrocytes, and oligodendrocytes) define brain homeostasis and are responsible for defense against neural tissue injury [50,51].…”

Section: No/cgmpmentioning

confidence: 99%

The Role of NO/cGMP Signaling on Neuroinflammation: A New Therapeutic Opportunity

Peixoto¹,

Nunes²,

Rapôso³

2017

Mechanisms of Neuroinflammation

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The nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling appears to play a key role in inhibiting neuroinflammation and preventing the activation of a proapoptotic pathway, thereby promoting neural cell survival. In addition, evidence indicates that cGMP/protein kinase G (PKG) pathway is involved in the modulation of glial cell activity. Phosphodiesterase 5 (PDE5), which hydrolyzes cGMP in the inactive form, 5ʹGMP, is present throughout the body and brain and has emerged as a potential therapeutic target for diseases related to neuroinflammatory and neurodegenerative processes, since their inhibition leads to accumulation of cGMP. The objective of this chapter is to review current knowledge of NO/cGMP signaling pathways on neuroinflammation and the potential therapeutic use of PDE5 inhibitors (PDE5-Is) in neurological diseases. The extensive, while recent, literature on the effects of PDE-Is on Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD), Huntington's disease (HD), and stroke has been reviewed.

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Homeostatic function of astrocytes: Ca2+ and Na+ signalling

Cited by 111 publications

References 142 publications

Translational potential of astrocytes in brain disorders

Translational potential of astrocytes in brain disorders

Astroglial calcium signalling in Alzheimer's disease

The Role of NO/cGMP Signaling on Neuroinflammation: A New Therapeutic Opportunity

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