Extract from the brain of young mice produced weak cytoproliferative effect on cultured glial cells, while brain extract from old mice 3-4-and 30-60-fold stimulated glial proliferation in primary and passaged cell cultures, respectively.
Key Words: cell culture; gliosis; brain aging; prion diseasesHuman and animal prion diseases (PD) are characterized by typical histopathological changes involving only the brain and, sometimes, spinal cord. They are characterized by neuronal loss, spongiform changes of the white and/or grey matter of the brain and spinal cord, formation of amyloid plagues, and gliosis. These changes considerably differ in various PD. Thus, amyloid plagues are observed in 9 and 70% patients with Creutzfeldt-Jacob disease (CJD) and kuru. respectively. However, gliosis is typical of all diseases including lethal hereditary insomnia, which is seldom characterized by spongiosis, but induces neuronal loss and astrogliosis in the mediodorsal and anterioventral thalamic nuclei [ 10].For a long time much attention was focused on the mechanism of PD-induced lesions in the central nervous system (CNS), plague origin, chemical composition, and topography, as well as topography of spongiform regions, mechanisms of neurodegeneration, and correlations between CNS damage and mutations in PRNP gene. At the same time, it was assumed that the initial histopathological changes are neuronal loss followed by spongiosis and accumulation of amyloid. This sequence culminates in glial reaction replacing defects (reactive gliosis) caused by progressive neuronal death [ 1]. Recently, the interest of many researchers was attracted to the role of glia in this multistage process of CNS damage by infectious (and other) proteins. In the late 80s, immunocytochemical and ultrastructural studies showed that, on one hand, glial cells are involved in phagocytosis of amyloid fibrils during AIzheimer disease (AD) [11,15], while on the other hand, they participate in the formation of amyloid fibrils during AD and CJD [9,14]. These data were confirmed by the discovery of activated microglia involved in the accumulation of amyloid during experimental scrapie m mice [2]. At the same time, variable and important role of microglia in the formation of amyloid plagues during PD was demonstrated. It was suggested that variability is specific for this nosologic form and realized on the level of mRNA synthesis for scrapie-associated amyloid protein precursor [7]. These data were supplemented by studies on the mechanisms of neuronal death. It was shown that synthetic peptide 106-126 homologous to amyloid protein isolated from the brain of patient died from Gerstmann--Straussler--Scheinker syndrome (GSSS) caused apoptotic death of neurons and pronounced proliferation of glial cells in culture [13]. Moreover. it was found that peptide 106-126 promotes in vitro formation of amyloid fibrils and is toxic for cultured neurons only in the presence of microglia responding to this peptide by enhanced generation of oxidative radicals [3].
