Authors: 
A. Stolzing, T. Grune
Category: 
Poster
Conference: 
Abstract: 

Introduction: Common symptoms of different neurodegenerative diseases start in the second half of the human life. Several of theses diseases, including Alzheimer’s and Parkinsons disease, are accompanied by severe disturbances of protein metabolism and homeostasis in the brain. Since microglial cells are to some extend responsible for the maintenance of this homeostasis, age related functional changes of the microglia are significant as is the possible restoration of normal function of adult microgilal cells.

Methods: We established the preparation of cultures of primary microglial cells isolated from adult animals (12 months). Protein synthesis and degradation were measured using intracellular labeling with S35-methionine. The activity of the proteasome was investigated in cytosol with the help of flurogenic peptides and the contend of proteasome was measured by immunoblot.

Results: Protein turnover was impaired in microglial cells from adult animals. Protein synthesis (only 60% of the rate of young microglia) and also the degradation of extracellular (17%) and intracellular (45%) proteins was decreased in micoglial cells from 12 month old Wistar rats. These changes were accompanied by a decline in proteasomal activity (27% for the ATP independent activity) compared to younger cells. The contend of 20S proteasom of the cells is not lower in adult versus young microglial cells. We were also able to demonstrate higher basal levels of ROS in adult microglial cells. However, in these cells, no oxidative burst occurs after PMA stimulation. The oxidative burst could be reactivated after we cultivated our primary microglial cells from adult rats with vitamin E.

Discussion: The adult microglial cells reveals different metabolic properties in comparison to the widely used microglial cells from newborn animals. Despite the fact that the use of microglial cells from newborn animals is easier to handle and more cells can be isolated, we suggest that microglial cells from adult animals may be better suited for the the study of neurodegenerative diseases. The changes occurring in adult mircoglial cells can to some extend be retarded in in vitro cultures by the use of vitamin E. Vitamin E decreases the amount of antiinflammatory products, like TNF-alpha, gamma-IFN, NO, IL-6 and IL-12. Whether this treatment is also valuable for in vivo studies has to be further explored in animal experiments.

Ref.:

1) Stolzing A, Wengner A, Grune T. Degradation of oxidized extracellular proteins by microglia. Arch Biochem Biophys. 2002 Apr 15;400(2):171-9.

2) Stolzing A, Grune T. The proteasome and its function in the ageing process. Clin Exp Dermatol. 2001 Oct;26(7):566-72. Review.

Keywords (Optional): 
Aging
Microglia
Proteasome
Vitamin E