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

Article type: Research Article

Authors: Schütze, Sandra^{a; *} | Loleit, Tobias^a | Zeretzke, Moritz^a | Bunkowski, Stephanie^a | Brück, Wolfgang^a | Ribes, Sandra^a | Nau, Roland^{a; b}

Affiliations: [a] Department of Neuropathology, University of Göttingen, Göttingen, Germany | [b] Department of Geriatrics, Evangelisches Krankenhaus Göttingen-Weende, Göttingen, Germany

Correspondence: [*] Correspondence to: Sandra Schütze, Department of Neuropathology, University of Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany. Tel.: +49 551 39 12889; Fax: +49 551 39 10800; E-mail: sebert1@gwdg.de.

Abstract: Activated microglia is considered to be involved in the progression of Alzheimer's disease (AD). We investigated the effect of amyloid-β1-40 (Aβ40) and exogenous agonists of Toll-like receptor (TLR) 1/2 (Pam3CSK4) 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 Pam3CSK4, LPS, and Aβ40. Combined treatment with Aβ40 and Pam3CSK4 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.

Keywords: Amyloid-β, co-cultures, computer-assisted analysis, Definiens Cognition Network Technology, LPS, microglia, neuronal injury, neuronal viability, Toll-like receptor, Pam₃CSK₄

DOI: 10.3233/JAD-2012-120856

Journal: Journal of Alzheimer's Disease, vol. 31, no. 3, pp. 651-657, 2012