Astroglial plasticity in hemizygous and heterozygous jimpy mice

Gliosis is a common phenomenon which occurs in many human diseases and in experimentally altered nervous tissue. The factors activating astrocytes to respond are still unclear but recent evidence suggests that diverse substances can provoke a gliotic response. This paper describes the nature of the gliosis in the myelin deficient jimpy and relates these findings to other recent studies of experimentally induced demyelination in which gliosis is a prominent feature of the disorder. In jimpy males, an astroglial hypertrophy which consists of an increase in the number of cell processes can be demonstrated by both electron microscopy and immunocytochemistry using antibodies to glial fibrillary acidic protein. Increased glial fibrillary acidic protein staining in the white matter of jimpy males correlates with the normal time of myelination in different tracts. The immunostaining is not, however, restricted to white matter. Increased staining can be demonstrated in spinal cord grey matter when hardly any myelinated fibers are present, it is especially prominent around blood vessels of both white and grey matter, and is found in the corpus callosum and in the underlying subventricular zone shortly before or at the time myelination begins in this tract. These observations suggest that the hypertrophy is not simply a response by the astrocyte to the absence of myelin sheaths. While an astroglial hypertrophy is dramatic in jimpy males, quantitative counts of astrocytes and electron microscopic autoradiograms do not reveal an increase in the total number of this cell type. These findings suggest that hyperplasia and hypertrophy of astrocytes may be under separate regulatory control with different factors involved in each phenomenon. In the female carriers of the jimpy gene, myelination is temporarily delayed during postnatal development but after several months, the amount of myelin, whether measured morphometrically or biochemically, reaches normal levels. In the white matter of the young female carrier, staining for glial fibrillary acidic protein is increased in terms of the number of processes and the total volume of neuropil but a normal pattern of staining is observed within a year. These and other observations suggest that the glial hypertrophy in the young mosaic is temporary and that regression and reorganization of glial processes takes place as myelination proceeds.