Beta-amyloid activated microglia induce cell cycling and cell death in cultured cortical neurons.
Immunocytochemical studies of postmortem human tissue have shown that the neurons at risk for degeneration in Alzheimer's are marked by the ectopic expression of several cell cycle components. The current work investigates the roles that beta-amyloid activated microglia might play in leading neurons to re-express cell cycle components. Stable cultures of E16.5 mouse cortical neurons were exposed to beta-amyloid alone, microglial cells alone, or microglial cells activated by beta-amyloid. Increased cell death was found in response to each of these treatments, however, only the amyloid activated microglial treatment increased the number of neurons that were positive for cell cycle markers such as PCNA or cyclin D and incorporation of BrdU. Double labeling with BrdU and TUNEL techniques verified that the 'dividing' neurons were dying, most likely through an apoptotic mechanism. The identity of the soluble factor(s) elaborated by the microglia remains unknown, but FGF2, a suspected neuronal mitogen, was ruled out. These results further support a model in which microglial activation by beta-amyloid is a key event in the progression in Alzheimer's disease.
Wu
Q
Q
Alzheimer Research Laboratory, University Hospitals of Cleveland, Case Western Reserve University, School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Combs
C
C
Cannady
S B
SB
Geldmacher
D S
DS
Herrup
K
K
D016229:Amyloid beta-Peptides / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D017077:Culture Media, Conditioned; D004622:Embryo, Mammalian; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology*
D016229:Amyloid beta-Peptides; D017077:Culture Media, Conditioned