Additive microglia-mediated neuronal injury caused by amyloid-ß 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-ß(1-40) (Aß(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 Aß(40). Combined treatment with Aß(40) and Pam(3)CSK(4) or LPS had an additive effect. Hence, in patients with AD, synergistic microglial activation by Aß and bacterial products during infections might contribute to disease progression.

Microglial cells and peritoneal macrophages release activin A upon stimulation with Toll-like receptor agonists.

Activin A levels are elevated in the cerebrospinal fluid (CSF) of patients with meningitis and in the sera of patients with sepsis. The source(s) of the elevated concentrations of activin A in CSF and serum have not yet been discovered. Here we demonstrate that primary mouse microglial cells and peritoneal macrophages release activin A after treatment with agonists of Toll-like receptor (TLR) 2, 4, and 9. These findings provide further evidence for a role of activin in the innate immune response and suggest that microglial cells and macrophages are a source of elevated activin A concentrations observed in the CSF during bacterial meningitis and in the systemic circulation during sepsis.