Chronic LPS treatment enhanced nuclear exclusion of TDP-43 in spinal neurons of hTDP-43^A315T transgenic mice.

<p>Transgenic mice expressing hTDP-43^A315T mutant at 6 months of age were i.p. injected with LPS (1mg/kg) or vehicle solution once per week for a period of 2 months. (A) Spinal cord sections from LPS and vehicle-treated mice were immunostained with monoclonal antibody specific for human TDP-43. As revealed by immunostaining, more neuronal cells in LPS-treated spinal cord sections exhibited loss of nuclear TDP-43 staining (first and second panels) than vehicle (third and fourth panels). Insets in the first and second panels show magnified motor neurons of LPS-treated mice with nuclear loss of TDP-43. Arrow heads in first and second panels show neurons exhibiting nuclear loss of TDP-43 in LPS-treated hTDP-43^A315T tg mice while arrows in third and fourth panel show neurons exhibiting nuclear loss of TDP-43 in vehicle-treated hTDP-43^A315T tg mice. All representative sections are from different mice for each treatment group. DAPI was used to stain nuclei. Scale bar = 50μm. (B) Number of spinal neurons per section exhibiting nuclear loss of TDP-43 was higher in LPS-treated mice as compared to vehicle-treated mice (<i>p</i> = 0.043 by student’s t test, N = 4, 6 spinal cord sections from 4 different animals at 8 months were analyzed for each group).