Interactions between Astrocytes and Oligodendroglia in Human and Experimental Creutzfeldt–Jakob Disease and Scrapie

Abstract

We report here a rare interaction between reactive astrocytes and oligodendrocytes, first detected in a brain biopsy of human Creutzfeldt–Jakob disease (CJD) and then in experimental CJD in mice and in two models (263K and 22CH) of scrapie in hamsters. In human CJD brain biopsy, low-power electron microscopy revealed numerous examples of astrocytes and oligodendroglial cells in close apposition. At higher magnification, both types of cells were occasionally connected by adhesive plaque junctions (attenuated desmosomes). More complex structures were also seen. Astrocytic cytoplasm was penetrated by oligodendroglial processes or oligodendroglial cells were completely surrounded by astrocytic processes. An analogous phenomenon was identified in the brains of CJD-infected mice and in two models of scrapie-infected hamsters. In the CJD brain biopsy and in brain specimens from CJD-infected mice and scrapie-infected hamsters, GFAP-immunoreactive hypertrophic astrocytes were readily identified, particularly in those areas where the tissue damage was the most extensive. Oligodendrocytes frequently surrounded hypertrophic astrocytic processes or cell bodies and remained unstained in GFAP preparation. The significance of the interactions between astrocytes and oligodendrocytes is unclear at the present time. As in MS and other brain pathologies in which it has been studied, this interaction is not associated with a reaction toward any infectious pathogen but it may be an early cellular event that triggers further brain tissue destruction.