UPTAKE AND SUBCELLULAR-DISTRIBUTION OF CR-51 IN GOMORI-POSITIVE ASTROCYTES IN PRIMARY CULTURE

An unusual population of astrocytes containing Gomori-positive inclusi ons occurs in periventricular regions of the brain in all mammalian sp ecies. The inclusions are autofluorescent and exhibit non-enzymatic pe roxidase activity. Estradiol treatment in vivo and cysteamine treatmen t in vitro have been shown to in crease the number and size of these i nclusions. Recent studies indicate that the Gomori inclusions are accu mulations of autophagocytized abnormal mitochondria. The mitochondrial changes initiating Gomori inclusion formation begin with a loss of cr istae. Energy dispersive X-ray microanalysis also reveals small emissi on peaks indicative of chromium. The appearance of chromium peaks in t he initial stages of mitochondrial transformation suggests that enhanc ed permeability to chromium could play a causal role in generating Gom ori in elusions. In the present study, we have examined the uptake and intracellular distribution of chromium during Gomori inclusion format ion in cysteamine-treated cultured astrocytes. Cr-51 was added to the media of glial cultures 24 hours prior to the initiation of the format ion of Gomori inclusions by the addition of cysteamine. Cultures were fixed and prep:ared for EM radioautography at 12, 24, and 72 hours fol lowing the addition of cysteamine. Cr was added to control cells but t hey were not treated with cysteamine, and, they did not, therefore, de velop Gomori inclusions. Cysteamine exposure resulted in a rapid susta ined increase in radiolabel over the astrocytes. Much of the label was concentrated over mitochondria. At the later time points, label conce ntrated progressively over developing Gomori inclusions. These results confirm that the onset of Gomori inclusion formation coincides with i ncrease cellular permeability to chromium and they indicate that uptak e of chromium by mitochondria may play an important role in initiating development of these structures. 1995 Intox Press, Inc.