Figure 3

Microglial p38α MAPK deficiency attenuates LPS-induced synaptic protein loss in microglia/neuron co-cultures. Mouse primary neurons (5 × 10⁴) were co-cultured with either p38α WT microglia or p38α KO microglia (2 × 10⁴) in the absence or presence of LPS (3 ng/ml) for 72 h. Neuronal lysates were analyzed by immunoblotting; a representative blot is shown in (A). The levels of the post-synaptic protein drebrin (B) but not PSD95 (C) were significantly decreased by LPS exposure in p38α WT microglia. However, LPS treatment of the p38α KO microglia/neuron co-cultures did not produce a significant decrease in drebrin or PSD95. (D) LPS treatment of p38α WT microglia/neuron co-cultures produced a significant decrease in synaptophysin levels, which was not seen in LPS stimulated co-cultures of p38α KO microglia/neurons. (E) Levels of syntaxin 1 were unaffected by LPS in either WT or KO microglia. (F) Levels of SNAP25 were significantly decreased in the LPS-stimulated p38α WT microglia co-cultures, but not in microglia co-cultures from p38α KO mice. (*p < 0.05; p38α WT vs. p38α WT+LPS). Data represents 2-3 independent experiments.