Astrocyte physiopathology: At the crossroads of intercellular networking, inflammation and cell death

Rossi, Daniela

doi:10.1016/j.pneurobio.2015.04.003

Cited by 156 publications

(110 citation statements)

References 569 publications

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“…Recent work suggests the current concept of brain networks, as intelligent contacts between several neurons should be expanded to include communications occurring between neurons and glial cells (Rossi, 2015;Santello et al, 2011;Volterra and Meldolesi, 2005). Astrocytes are best viewed as local 'hubs' that can receive and integrate information from thousands of synapses, other glial cells and blood vessels (Bushong et al, 2002;Rossi, 2015;Santello et al, 2011;Volterra and Meldolesi, 2005).…”

Section: Synaptogenesis Gliotransmission and Circuit Integrationmentioning

confidence: 99%

Inflammation, Glutamate, and Glia: A Trio of Trouble in Mood Disorders

Haroon

Miller

Sanacora

2016

Neuropsychopharmacol

358

291

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Increasing data indicate that inflammation and alterations in glutamate neurotransmission are two novel pathways to pathophysiology in mood disorders. The primary goal of this review is to illustrate how these two pathways may converge at the level of the glia to contribute to neuropsychiatric disease. We propose that a combination of failed clearance and exaggerated release of glutamate by glial cells during immune activation leads to glutamate increases and promotes aberrant extrasynaptic signaling through ionotropic and metabotropic glutamate receptors, ultimately resulting in synaptic dysfunction and loss. Furthermore, glutamate diffusion outside the synapse can lead to the loss of synaptic fidelity and specificity of neurotransmission, contributing to circuit dysfunction and behavioral pathology. This review examines the fundamental role of glia in the regulation of glutamate, followed by a description of the impact of inflammation on glial glutamate regulation at the cellular, molecular, and metabolic level. In addition, the role of these effects of inflammation on glia and glutamate in mood disorders will be discussed along with their translational implications.

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Section: Synaptogenesis Gliotransmission and Circuit Integrationmentioning

confidence: 99%

Inflammation, Glutamate, and Glia: A Trio of Trouble in Mood Disorders

Haroon

Miller

Sanacora

2016

Neuropsychopharmacol

358

291

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“…5 astroglia may undergo structural or functional atrophy with a loss of function, pathological remodelling or reactivity; these changes can develop on their own or in combination [70,72]. Reactive astrogliosis is an evolutionary conserved defensive reaction, which results in a complex structural, biochemical and functional remodelling of astrocytes leading to an appearance of multiple reactive phenotypes, which again seem to be context/disease specific.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

“…In the animal model of ALS expressing human mutant superoxide dismutase 1 (Tg(SOD1*G93A)1Gur mice), the emergence of atrophic astrocytes is the earliest pathological signature [81][82][83]; these atrophic astrocytes down-regulate glutamate uptake and become vulnerable to glutamate by themselves. Deficient astrocytes, therefore, provide a background for developing glutamate excitotoxicity that leads to neuronal death [72]. Incidentally, a cell-specific silencing of the mutant SOD1 gene in astrocytes significantly delayed development of clinical symptoms [84].…”

Section: A C C E P T E D Accepted Manuscriptmentioning

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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“…TLR-2 functions as a master sentry receptor to detect neuronal death and tissue damage in many different neurological conditions including nerve trans-section injury, traumatic brain injury and hippocampal excitotoxicity . Astrocytes, the other cellular actor of neuroinflammation (Ranshoff and Brown, 2012) are also able to sense tissue injury via TLR-3 (Farina et al, 2007;Rossi, 2015).…”

Section: How Does This Key Event Relationship Workmentioning

confidence: 99%