title: Reactive astroglia-neuron relationships in the human cerebellar cortex: a quantitative, morphological and immunocytochemical study in Creutzfeldt-Jakob disease.
abstract: In order to investigate the role of neuron-glia interactions in the response of astroglial to a non-invasive cerebellar cortex injury, we have used two cases of the ataxic form of Creutzfeldt-Jakob disease (CJD) with distinct neuronal loss and diffuse astrogliosis. The quantitative study showed no changes in cell density of either Purkinje or Bergmann glial cells in CJ-1, whereas in the more affected CJ-2 a loss of Purkinje cells and an increase of Bergmann glial cells was found. The granular layer in both CJD cases showed a similar loss of granule cells (about 60%) in parallel with the significant increase in GFAP+ reactive astrocytes. GFAP immunostaining revealed greater reactivity of Bergmann glia in CJ-2 than in CJ-1, as indicated by the thicker glial processes and the higher optical density. Granular layer reactive astrocytes were regularly spaced. In both CJD cases there was strict preservation of the spatial arrangement of all astroglial subtypes--Fañanas cells, Bergmann glia and granular layer astrocytes. Reactive Fañanas and Bergmann glial cells and microglia/macrophages expressed vimentin, while only a few vimentin+ reactive astrocytes were detected in the granular layer. Karyometric analysis showed that the increase in nuclear volume in reactive astroglia was directly related with the level of glial 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 spines were ensheathed by lamellar processes of reactive Bergmann glia. Our results suggest that quantitative (neuron/astroglia ratio) and qualitative changes in the interaction of neurons with their region-specific astroglial partners play a central role in the astroglial response pattern to the pathogenic agent of CJD.
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine, Cardenal Herrera Oria s/n, Santander, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Lafarga
authors.forename: M T
authors.initials: MT
authors.lastname: Berciano
authors.forename: I
authors.initials: I
authors.lastname: Saurez
authors.forename: M A
authors.initials: MA
authors.lastname: Andres
authors.forename: J
authors.initials: J
authors.lastname: Berciano
mesh_terms: D001253:Astrocytes / Q000502:physiology*; D001259:Ataxia / Q000473:pathology; D002466:Cell Nucleolus / Q000648:ultrastructure; D002467:Cell Nucleus / Q000648:ultrastructure; D002525:Cerebellar Cortex / Q000473:pathology*; D007562:Creutzfeldt-Jakob Syndrome / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007621:Karyotyping; D009457:Neuroglia / Q000502:physiology*; D009469:Neuromuscular Junction / Q000648:ultrastructure; D009474:Neurons / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology / Q000648:ultrastructure; D014746:Vimentin / Q000276:immunology / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D014746:Vimentin