Impairment of protein homeostasis and decline of proteasome activity in microglial cells from adult Wistar rats.
Common symptoms of different neurodegenerative diseases start to develop in the second half of the human life. Several of these diseases, including Alzheimer's and Parkinson's disease, are accompanied by severe disturbances of protein metabolism and homeostasis in the brain. Because microglial cells are, to some extent, responsible for the maintenance of this homeostasis, age-related functional changes of the microglia are important. We established, therefore, the preparation of cultures of primary microglial cells isolated from adult animals in comparison to the widely used standard model, primary microglial cells isolated from newborn animals. In addition, we investigated changes in the activation and in the protein homeostasis within these cells. The protein turnover seems to be significantly impaired in microglial cells isolated from adult animals and this seems to be accompanied by a decline in proteasomal function, but not in the protease content. We were also able to demonstrate higher cell surface molecule expression and a higher basal NO release of microglia isolated from adult animals in comparison to the microglia isolated from newborn rats; however, the PMA stimulated oxidative burst was abolished completely in cells from adult animals. Microglia from adult animals were also not able to upregulate their protein metabolism after activation. From these investigations it was concluded that microglial cells from adult animals have significantly different metabolic properties in comparison to the widely used microglial cells from newborn animals.
Stolzing
Alexandra
A
Neuroscience Research Center, Medical Faculty (Charité), Humboldt University Berlin, Germany.
Grune
Tilman
T
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000367:Age Factors; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006213:Hallucinogens / Q000494:pharmacology; D006706:Homeostasis; D037102:Lectins / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009097:Multienzyme Complexes / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000032:analysis; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D013997:Time Factors
D000662:Amphetamines; D019013:CD40 Antigens; D005904:Glial Fibrillary Acidic Protein; D006213:Hallucinogens; D037102:Lectins; D016177:Macrophage-1 Antigen; D009097:Multienzyme Complexes; C524898:PLAUR protein, human; C524900:Plaur protein, rat; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D017493:Leukocyte Common Antigens; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C100230:4-methoxyamphetamine