Stratification of astrocytes in healthy and diseased brain

Verkhratsky, Alexei; Zorec, Robert; Parpura, Vladimir

doi:10.1111/bpa.12537

Cited by 201 publications

(169 citation statements)

References 299 publications

(271 reference statements)

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“…In conclusion, the studies presented here and in other review articles (34,163) show that astrocytes and oligodendroglial cells (136,137) may have an underappreciated spectrum of roles to play in mechanisms NDD. Thus, the time may now have arrived for astrocytes and oligodendroglia to receive more attention and become the focus of studies of NDD mechanisms as well for investigating potential NDD therapies.…”

Section: Resultssupporting

confidence: 53%

Protein astrogliopathies in human neurodegenerative diseases and aging

2017

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Neurodegenerative diseases are characterized by progressive dysfunction and loss of neurons associated with depositions of pathologically altered proteins showing hierarchical involvement of brain regions. The role of astrocytes in the pathogenesis of neurodegenerative diseases is explored as contributors to neuronal degeneration or neuroprotection pathways, and also as potential mediators of the transcellular spreading of disease-associated proteins. Protein astrogliopathy (PAG), including deposition of amyloid-β, prion protein, tau, α-synuclein, and very rarely transactive response DNA-binding protein 43 (TDP-43) is not unprecedented or unusual in neurodegenerative diseases. Morphological characterization of PAG is considered, however, only for the neuropathological diagnosis and classification of tauopathies. Astrocytic tau pathology is seen in primary frontotemporal lobar degeneration (FTLD) associated with tau pathologies (FTLD-Tau), but also in the form of aging-related tau astrogliopathy (ARTAG). Importantly, ARTAG shares common features with primary FTLD-Tau as well as with the astroglial tau pathologies that are thought to be hallmarks of a brain injury related tauopathy known as chronic traumatic encephalopathy (CTE). Supported by experimental observations, the morphological variability of PAG might reflect distinct pathogenic involvement of different astrocytic populations. PAG might indicate astrocytic contribution to spreading or clearance of disease-associated proteins, however, this might lead to astrocytic dysfunction and eventually contribute to the degeneration of neurons. Here we review recent advances in understanding ARTAG and other related forms of PAG.

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Section: Resultssupporting

confidence: 53%

Protein astrogliopathies in human neurodegenerative diseases and aging

2017

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“…It is also reproduced in animal models of these diseases (Olabarria et al, 2010;Sullivan, Bjorkman, Miller, Colditz, & Pow, 2010). In addition, astrocytes may be directly or primarily targeted by the disease process, like in Alexander disease caused by Gfap mutation (Messing, 2018) or neuromyelitis optica caused by autoantibodies against the astrocyte protein aquaporin 4 [see (Verkhratsky, Zorec, & Parpura, 2017) for a complete review].…”

Section: Do Reactive Astrocytes Eventually Die?mentioning

confidence: 99%

Questions and (some) answers on reactive astrocytes

Escartin

Guillemaud

Sauvage

2019

Glia

233

180

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Astrocytes are key cellular partners for neurons in the central nervous system. Astrocytes react to virtually all types of pathological alterations in brain homeostasis by significant morphological and molecular changes. This response was classically viewed as stereotypical and is called astrogliosis or astrocyte reactivity. It was long considered as a nonspecific, secondary reaction to pathological conditions, offering no clues on disease‐causing mechanisms and with little therapeutic value. However, many studies over the last 30 years have underlined the crucial and active roles played by astrocytes in physiology, ranging from metabolic support, synapse maturation, and pruning to fine regulation of synaptic transmission. This prompted researchers to explore how these new astrocyte functions were changed in disease, and they reported alterations in many of them (sometimes beneficial, mostly deleterious). More recently, cell‐specific transcriptomics revealed that astrocytes undergo massive changes in gene expression when they become reactive. This observation further stressed that reactive astrocytes may be very different from normal, nonreactive astrocytes and could influence disease outcomes. To make the picture even more complex, both normal and reactive astrocytes were shown to be molecularly and functionally heterogeneous. Very little is known about the specific roles that each subtype of reactive astrocytes may play in different disease contexts. In this review, we have interrogated researchers in the field to identify and discuss points of consensus and controversies about reactive astrocytes, starting with their very name. We then present the emerging knowledge on these cells and future challenges in this field.

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“…Pathological changes in astrocytes are multifaceted and are disease and disease-stage specific. Conceptually, astrogliopathology is sub-classified into (i) reactive astrogliosis and (ii) astrocytopathies represented by astodegeneration with astroglial atrophy and loss of function and astroglial pathological remodelling [65,66,70].…”

Section: Principles Of Astrogliopathologymentioning

confidence: 99%

Astroglia in Sepsis Associated Encephalopathy

Shulyatnikova

Verkhratsky

2019

Neurochem Res

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Cellular pathophysiology of sepsis associated encephalopathy (SAE) remains poorly characterised. Brain pathology in SAE, which is manifested by impaired perception, consciousness and cognition, results from multifactorial events, including high levels of systemic cytokines, microbial components and endotoxins, which all damage the brain barriers, instigate neuroinflammation and cause homeostatic failure. Astrocytes, being the principal homeostatic cells of the central nervous system contribute to the brain defence against infection. Forming multifunctional anatomical barriers, astroglial cells maintain brain-systemic interfaces and restrict the damage to the nervous tissue. Astrocytes detect, produce and integrate inflammatory signals between immune cells and cells of brain parenchyma, thus regulating brain immune response. In SAE astrocytes are present in both reactive and astrogliopathic states; balance between these states define evolution of pathology and neurological outcomes. In humans pathophysiology of SAE is complicated by frequent presence of comorbidities, as well as age-related remodelling of the brain tissue with senescence of astroglia; these confounding factors further impact upon SAE progression and neurological deficits.

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Stratification of astrocytes in healthy and diseased brain

Cited by 201 publications

References 299 publications

Protein astrogliopathies in human neurodegenerative diseases and aging

Protein astrogliopathies in human neurodegenerative diseases and aging

Questions and (some) answers on reactive astrocytes

Astroglia in Sepsis Associated Encephalopathy

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