Article

Astrocytes: Biology and pathology

Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1763, USA.
Acta Neuropathologica (Impact Factor: 10.76). 12/2009; 119(1):7-35. DOI: 10.1007/s00401-009-0619-8
Source: PubMed

ABSTRACT

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.

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Available from: Michael V Sofroniew
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    • "Moreover, the most abundant and largest glial cell type in the spinal cord is astrocytes. Even though the morphologicall structures of astrocytes are the same, these cells can be classified into two types: protoplasmic and fibrous astrocytes, which are located in gray and white matter, respectively (Sofroniew and Vinters, 2010;Molofsky et al., 2012). Astrocytes play effective roles in supporting neurons in terms of neuroprotection, transmission of neurotransmitters, and regulation of neurogenesis (Tsacopoulos and Magistretti, 1996;Goldman, 2003;Newman, 2003). "

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    • "Reactive astrogliosis is the cellular and biochemical transformation of astrocytes in response to brain injury, and it significantly impacts—both positively and negatively—neural regeneration (Sofroniew and Vinters, 2010; Williams et al., 2007). Reactive astrogliosis was once thought to be an all-or-nothing transformation , but emerging evidence suggests that reactive astrocytes (RAs) are highly dynamic and tailor their transcriptional response to the type of injury and the region in which it occurs (Zamanian et al., 2012). "
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    ABSTRACT: Reactive astrogliosis is an essential and ubiquitous response to CNS injury, but in some cases, aberrant activation of astrocytes and their release of inhibitory signaling molecules can impair endogenous neural repair processes. Our lab previously identified a secreted intercellular signaling molecule, called endothelin-1 (ET-1), which is expressed at high levels by reactive astrocytes in multiple sclerosis (MS) lesions and limits repair by delaying oligodendrocyte progenitor cell (OPC) maturation. However, as ET receptors are widely expressed on neural cells, the cell- and receptor-specific mechanisms of OPC inhibition by ET-1 action remain undefined. Using pharmacological approaches and cell-specific endothelin receptor (EDNR) ablation, we show that ET-1 acts selectively through EDNRB on astrocytes—and not OPCs—to indirectly inhibit remyelination. These results demonstrate that targeting specific pathways in reactive astrocytes represents a promising therapeutic target in diseases with extensive reactive astrogliosis, including MS.
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