Role of glial filaments in cells and tumors of glial origin: a review

Abstract

In the adult human brain, normal astrocytes constitute nearly 40% of the total central nervous system (CNS) cell population and may assume a star-shaped configuration resembling epithelial cells insofar as the astrocytes remain intimately associated, through their cytoplasmic extensions, with the basement membrane of the capillary endothelial cells and the basal lamina of the glial limitans externa. Although their exact function remains unknown, in the past, astrocytes were thought to subserve an important supportive role for neurons, providing a favorable ionic environment, modulating extracellular levels of neurotransmitters, and serving as spacers that organize neurons. In immunohistochemical preparations, normal, reactive, and neoplastic astrocytes may be positively identified and distinguished from other CNS cell types by the expression of the astrocyte-specific intermediate filament glial fibrillary acidic protein (GFAP). Glial fibrillary acidic protein is a 50-kD intracytoplasmic filamentous protein that constitutes a portion of, and is specific for, the cytoskeleton of the astrocyte. This protein has proved to be the most specific marker for cells of astrocytic origin under normal and pathological conditions. Interestingly, with increasing astrocytic malignancy, there is progressive loss of GFAP production. As the human gene for GFAP has now been cloned and sequenced, this review begins with a summary of the molecular biology of GFAP including the proven utility of the GFAP promoter in targeting genes of interest to the CNS in transgenic animals. Based on the data provided the authors argue cogently for an expanded role of GFAP in complex cellular events such as cytoskeletal reorganization, maintenance of myelination, cell adhesion, and signaling pathways. As such, GFAP may not represent a mere mechanical integrator of cellular space, as has been previously thought. Rather, GFAP may provide docking sites for important kinases that recognize key cellular substrates that enable GFAP to form a dynamic continuum with microfilaments, integrin receptors, and the extracellular matrix.

Brain Contains a Functional Glucose-6-Phosphatase Complex Capable of Endogenous Glucose Production

“…Immunocytochemical analysis (Fig. 4A) shows that nearly all the cells stained positively for GFAP, a marker for brain astrocytes (32), and negatively for fibronectin and myelin basic protein, which are markers of fibroblasts and oligodendrocytes, respectively (31). Western blot analysis confirmed that the primary astrocytes from wild-type, Glc-6-Pase-␣ Ϫ/Ϫ , or Glc-6-PT Ϫ/Ϫ pups express GFAP (Fig.…”

“…The purity of the astrocytes was determined by staining for GFAP (32). The cells were fixed for 10 min in 4% paraformaldehyde, incubated for 30 min at room temperature in TST buffer (0.05 M Tris-HCl, pH 7.5, 0.15 M NaCl, and 0.1% Triton-X-100) containing 1% bovine serum albumin (BSA) and 10% horse serum (TST-BSA), and then incubated overnight at 4°C with a rabbit anti-GFAP antibody at 4 g/ml in TST-BSA.…”

Identification and cloning of human astrocyte genes displaying elevated expression after infection with HIV-1 or exposure to HIV-1 envelope glycoprotein by rapid subtraction hybridization, RaSH

“…Glial cells are the predominant cell type in the brain, constituting more than 50% of the total cell count and outnumbering neurons 10-fold (Pope, 1978;Rutka et al, 1997). Two major subtypes of glia are distinguished by their distinct functions in the nervous system: oligodendrocytes, which form myelin sheaths around nerve cell axons, and astrocytes, which maintain brain homeostasis and respond to pathogens and brain injury (Benveniste, 1992;Verkhratsky et al, 1998).…”

Intraretinal changes in the presence of epiretinal traction

“…Müller cells play a central role in retinal repair processes after injury. In particular, GFAP is involved in cell adhesion mechanisms, interacting with the cytoskeleton, surface receptors, and extracellular matrix in glia [23,[35][36][37]. In addition, the formation of epiretinal traction involves intraretinal glial proliferation, which hitherto has been considered predominantly epiretinal [38].…”

“…The contraction of this tissue induces centripetal tangential traction upon the underlying retinal layers, producing changes in the inner and outer layers. [22][23][24][25][26][27][28] Although the pathogenesis appears to be epiretinal, macular changes are not confined to the vitreomacular interface (VMI). Recent studies have hypothesized that iERM may induce intraretinal changes due to the tangential vector forces associated with the expression rate of glial fibrillary acid protein (GFAP).…”