Additive microglia-mediated neuronal injury caused by amyloid-β and bacterial TLR agonists in murine neuron-microglia co-cultures quantified by an automated image analysis using cognition network technology.
Activated microglia is considered to be involved in the progression of Alzheimer's disease (AD). We investigated the effect of amyloid-β(1-40) (Aβ(40) and exogenous agonists of Toll-like receptor (TLR) 1/2 (Pam(3)CSK(4)) and TLR4 (LPS) on neurons in primary murine neuron-microglia co-cultures. Neuronal viability, assessed by quantifying the number of intact neuronal extensions and their crossings using a newly developed Definiens Cognition Network Technology-based method, was significantly decreased after treatment with Pam(3)CSK(4), LPS, and Aβ(40). Combined treatment with Aβ(40) and Pam(3)CSK(4) or LPS had an additive effect. Hence, in patients with AD, synergistic microglial activation by Aβ and bacterial products during infections might contribute to disease progression.
Department of Neuropathology, University of Göttingen, Göttingen, Germany. sebert1@gwdg.de
Sandra
S
Schütze
Tobias
T
Loleit
Moritz
M
Zeretzke
Stephanie
S
Bunkowski
Wolfgang
W
Brück
Sandra
S
Ribes
Roland
R
Nau
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D018920:Coculture Techniques / Q000379:methods; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D055666:Lipopeptides / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000382:microbiology / Q000473:pathology*; D009415:Nerve Net / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000382:microbiology / Q000473:pathology*; D010446:Peptide Fragments / Q000633:toxicity*; D051193:Toll-Like Receptors / Q000819:agonists* / Q000502:physiology
D016229:Amyloid beta-Peptides; D055666:Lipopeptides; D008070:Lipopolysaccharides; C508075:Pam(3)CSK(4) peptide; D010446:Peptide Fragments; D051193:Toll-Like Receptors; C078592:amyloid beta-protein (1-40)