Astrocyte heterogeneity in the brain: from development to disease

Schitine, Clarissa; Nogaroli, Luciana; Costa, Marcos Romualdo; Hedin-Pereira, Cecília

doi:10.3389/fncel.2015.00076

Cited by 107 publications

(93 citation statements)

References 98 publications

(166 reference statements)

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“…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). In the gray matter astrocytes divide (through the process known as tiling that starts in the late embryogenesis) the parenchyma into relatively independent units, traditionally known as neurovascular units and recently often called astroglio-vascular units, that integrate, within an individual astroglial territorial domain, neural and vascular elements (Bushong et al ., 2002; Iadecola and Nedergaard, 2007; Nedergaard et al ., 2003).…”

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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“…Others have demonstrated regional differences among astrocytes in the expression of cytoskeletal elements and neuropeptides, and in the uptake of neurotransmitters (Wilkin et al, 1990). Regional differences in astrocytes have been observed in a variety of disease states, including Alzheimer’s Disease, amyotrophic lateral sclerosis, and major depression (Schitine et al, 2015). However, in many of these situations, it has been unclear whether the regional differences in astrocytes are due to intrinsic differences in the astrocytes themselves or to regional differences in neuronal pathology.…”

Section: Discussionmentioning

confidence: 99%

“…Regional differences in astrocyte physiology exist across the brain (Bonthius and Steward, 1993; Schitine et al, 2015). Thus, astrocytes in some regions may be differently affected by certain GFAP mutations than astrocytes in other regions.…”

Section: Introductionmentioning

confidence: 99%

Alexander Disease

Bonthius

Karaçay

2015

J Child Neurol

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Alexander disease is a genetically-induced leukodystrophy, due to dominant mutations in the glial fibrillary acidic protein (GFAP) gene, causing dysfunction of astrocytes. We have identified a novel GFAP mutation, associated with a novel phenotype for Alexander disease. A boy with global developmental delay and hypertonia was found to have a leukodystrophy. Genetic analysis revealed a heterozygous point mutation in exon 6 of the GFAP gene. The guanine-to-adenine change causes substitution of the normal glutamic acid codon (GAG) with a mutant lysine codon (AAG) at position 312 (E312K mutation). At the age of four years, the child developed epilepsia partialis continua, consisting of unabating motor seizures involving the unilateral perioral muscles. Epilepsia partialis continua has not previously been reported in association with Alexander disease. Whether and how the E312K mutation produces pathologic changes and clinical signs that are unique from other Alexander disease-inducing mutations in GFAP remain to be determined.

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“…Recent studies have reported that the dysfunction of these may lead to the development of various neuropathological diseases, such as major depression. 13) Actually, it has been demonstrated that both proliferations of neurons and astrocytes are inhibited in the cortex. 14) Moreover, histopathological studies have demonstrated a decrease in the density of astrocytes in postmortem brain tissue in major depression.…”

Section: )mentioning

confidence: 99%

Corticosterone Inhibits the Proliferation of C6 Glioma Cells <i>via</i> the Translocation of Unphosphorylated Glucocorticoid Receptor

Nakatani

Amano

Takeda

2016

Biological & Pharmaceutical Bulletin

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Astroglial cells have been considered to have passive brain function by helping to maintain neurons.However, recent studies have revealed that the dysfunction of such passive functions may be associated with various neuropathological diseases, such as schizophrenia, Alzheimer's disease, amyotrophic lateral sclerosis and major depression. Corticosterone (CORT), which is often referred to as the stress hormone, is a well-known regulator of peripheral immune responses and also shows anti-inflammatory properties in the brain. However, it is still obscure how CORT affects astroglial cell function. In this study, we investigated the effects of CORT on the proliferation and survival of astroglial cells using C6 glioma cells. Under treatment with CORT for 24h, the proliferation of C6 glioma cells decreased in a dose-dependent manner. Moreover, this inhibition was diminised by treatment with mifepristone, a glucocorticoid receptor (GR) antagonist, but not by spironolactone, a mineralocorticoid receptor (MR) antagonist, and was independent of GR phosphorylation and other GR-related intracellular signaling cascades. Furthermore, it was observed that the translocation of GR from the cytosol to the nucleus was promoted by the treatment with CORT. These results indicate that CORT decreases the proliferation of C6 glioma cells by modifying the transcription of a particular gene related to cell proliferation independent of GR phosphorylation.

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Astrocyte heterogeneity in the brain: from development to disease

Cited by 107 publications

References 98 publications

Translational potential of astrocytes in brain disorders

Translational potential of astrocytes in brain disorders

Alexander Disease

Corticosterone Inhibits the Proliferation of C6 Glioma Cells <i>via</i> the Translocation of Unphosphorylated Glucocorticoid Receptor

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