Glia Fibrillary Acidic Protein Research Articles

Synergistic action of thyroid hormone, insulin and hydrocortisone on astrocyte differentiation

We report here on the synergistic regulation of astrocyte development by 3 hormones: thyroid hormone (TH), insulin, and hydrocortisone (HC). Their effect, in a defined serum-free media, on astrocyte morphology, on glia fibrillary acidic protein (GFAP) immunostaining pattern, and on glutamine synthetase (GS) was investigated. TH transformed the flat, polygonal astrocytes into process-bearing cells. This effect was accentuated by insulin, which by itself had no effect on astrocyte morphology. The morphological transformations were accompanied by changes in the pattern of GFAP immunostaining which indicated a more organized and directed cytoskeleton arrangement in the TH-insulin treated cultures. Over 95% of the cells in the culture expressed GFAP. All 3 hormones regulated GS levels. TH increased GS levels by 50% and insulin raised its levels by 3-fold. While having no effect on astrocyte morphology, HC increased GS levels by 3.7-fold in both the hormone-free and insulin-supplemented medium. HC acted synergistically with insulin in its action on GS bringing about a 12-fold increase in the enzyme activity. In contrast, TH did not interact with insulin and was additive with HC in its action on GS. The continuous presence of insulin and TH was required to maintain their morphological and GS effect, suggesting that these hormones might not only be important for astrocyte differentiation, but later on for astrocyte function as well. Since astrocytes interact with and affect neurons and oligodendrocytes, the findings reported here might have bearing on the development and function of these other brain cells as well.

Autocrine regulation of glial proliferation and differentiation: The induction of cytodifferentiation of postmitotic normal glioblast by growth-promoting factor from astrocytoma cell

A growth-promoting factor (GPF) from astrocytoma cells (GA-1) cultured in serum-free medium (N2) exerted on normal glioblasts proliferative and differentiation-promoting effects, which have been observed in glia maturation factor (GMF) stimulation. The serum-free conditioned media of GA-1 provoked DNA synthesis of glioblasts, and subsequently elicited a morphological differentiation characterized by the extrusion of processes as well as biochemical changes including an increased cellular level of glia fibrillary acidic protein (GFA protein), S-100 protein, and α-enolase. The transforming growth factor activity was also found in the media. Partially purified GPF had a molecular weight range of 7100–10,000 M r and acidic isoelectric point (pH 4.6), and showed a susceptibility to heat treatment and denaturation at low and high pHs. The present results and the findings accumulated from our previous studies on gliotrophic growth factors provide a general concept of the growth and differentiation regulations of normal or neoplastic glial cells by growth factors through autocrine systems.

Influence of grafted glia cells and host mossy fibers on anomalously migrated host granule cells surviving in cortical transplants

Embryonic cerebral cortex was transplanted over the cerebellum of one- to two-day-old rats. In mature rats, clusters of granule cells that failed to migrate into the internal granule cell layer were now found within the graft tissue. Immunocytochemical staining of astrocytic glial cells in the cortical transplants revealed that glial processes were distributed in an unusual polarized orientation in those regions that contained host granule cells. Other areas of the graft exhibited glia cells with processes that projected radially from their cell body, thus resembling fibrous astrocytes. Fibrous astrocytes in transplants, however, were more heavily stained than similar glial cells in the intact cerebral cortex of the host, indicating a quantitative difference in the glia fibrillary acidic protein. Acetylcholinesterase-positive fibers were observed between the clusters of granule cells in the cortical grafts. Such fibers traversed the molecular layer and, since they could be traced from the white matter of the host cerebellum, they were presumed to be mossy fibers. It is concluded that migration of external granule cells in the cerebellum can be altered by placing embryonic cerebral cortex next to the developing cerebellum. Granule cells that have migrated into the grafted cerebral cortical tissue nevertheless receive afferent fibres.