REACTIVE ASTROGLIA NEURON RELATIONSHIPS IN THE HUMAN CEREBELLAR CORTEX - A QUANTITATIVE, MORPHOLOGICAL AND IMMUNOCYTOCHEMICAL STUDY IN CREUTZFELDT-JAKOB DISEASE

In order to investigate the role of neuron-glia interactions in the re sponse of astroglial to a non-invasive cerebellar cortex injury, we ha ve used two cases of the ataxic form of Creutzfeldt-Jakob disease (CJD ) with distinct neuronal loss and diffuse astrogliosis. The quantitati ve study showed no changes in cell density of either Purkinje or Bergm ann glial cells in CJ-1, whereas in the more affected CJ-2 a loss of P urkinje cells and an increase of Bergmann glial cells was found. The g ranular layer in both CJD cases showed a similar loss of granule celts (about 60%) in parallel with the significant increase in GFAP+ reacti ve astrocytes. GFAP immunostaining revealed greater reactivity of Berg mann glia in CJ-2 than in CJ-1, as indicated by the thicker glial proc esses and the higher optical density. Granular layer reactive astrocyt es were regularly spaced. In both CJD cases there was strict preservat ion of the spatial arrangement of all astroglial subtypes-Fananas cell s, Bergmann glia and granular layer astrocytes. Reactive Fananas and B ergmann glial cells and microglia/macrophages expressed vimentin, whil e only a few vimentin+ reactive astrocytes were detected in the granul ar layer. Karyometric analysis showed that the increase in nuclear vol ume in reactive astrloglia was directly related with the level of glia l hypertrophy. The number of nucleoli per nuclear section was constant in astroglial cells of human controls and CJD, suggesting an absence of polyploidy in reactive astroglia. Ultrastructural analysis revealed junctional complexes formed by the association of macula adherens and gap junctions. In the molecular layer numerous vacant dendritic spine s were ensheathed by lamellar processes of reactive Bergmann glia. Our results suggest that quantitative (neuron/astroglia ratio) and qualit ative changes in the interaction of neurons with their region-specific astroglial partners play a central role in the astroglial response pa ttern to the pathogenic agent of CJD.