Altered cellular distribution of iron in the central nervous system of myelin deficient rats.

Under normal conditions, iron is found predominantly in oligodendrocytes, the myelin producing cell, in the rat brain. A genetic mutant strain of rats known as myelin deficient rats is examined in the present study because their number of oligodendrocytes is decreased and those oligodendrocytes present are structurally abnormal. The levels of iron in the liver (major site of iron storage) and in the pons-cerebellum did not differ statistically between the myelin deficient rats and the littermate control rats, whereas only half of the iron normally found in the cerebrum-midbrain was present in the myelin deficient rat. Histologically, iron was found predominantly in oligodendrocytes in the littermate control rats, as expected. In the myelin deficient rat, iron staining was confirmed to astrocytes and microglia. The results of this study strongly suggest that iron uptake into the brain continues in the absence of normal oligodendrocytes and myelin. Furthermore, these data suggest that iron metabolism can be substantially altered, as indicated by the accumulation of iron in astrocytes and microglia, when normal or near normal levels of iron are quantitatively demonstrated. The response of astrocytes and microglia to sequester the iron (presumably through phagocytosis) in the absence of invasive damage represents, to our knowledge, a new functional observation for these cells. Based on these observations it is clear that iron histochemistry in combination with quantitative analysis is necessary to interpret data regarding iron physiology, at least in neurobiology, and iron accumulation by astrocytes and microglia may provide clues of altered iron metabolism despite normal iron levels.