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Fig. 5 | Acta Neuropathologica Communications

Fig. 5

From: Nuclear poly(ADP-ribose) activity is a therapeutic target in amyotrophic lateral sclerosis

Fig. 5

Veliparib inhibits TDP-43-associated neuronal loss in rat spinal cord cultures. a. The spinal cord was isolated from Sprague Dawley embryos (E16-E18), dissociated with protease and DNase, and seeded onto astrocyte coated 12-well plates. After 1 day in vitro (1 DIV) cell proliferation was stopped by the addition of 5 μM cytosine arabinoside (AraC). At 14 DIV cultures were infected with a LacZ control or TDP-43 attenuated herpes simplex virus alongside DMSO or Veliparib. At 19 DIV the neurons were fixed and immunostained for the neuronal marker neurofilament-H (NF-H) and counterstained with Hoescht. Five images (10X magnification) were captured from each condition and neuronal cell bodies were counted. Each condition was repeated three times from 3 independent cultures. b. Viral infection of TDP-43 leads to the loss of neuronal cell bodies in dose-dependent manner. Co-treatment with 1 μM or 5 μM Veliparib inhibits TDP-43-induced neuronal cell loss. Mean (± SEM) is presented, each data point represents three technical repeats from an independent culture. 1X represents a virus titer of 3-5 × 104 pfu/ml. Two-way ANOVA (p < 0.0001) and a Dunnett’s test for significance was performed. NS: not significant. c. Example images (magnification 10X), of rat spinal-cord cultures infected with 1X LacZ or 1X TDP-43 and incubated with DMSO or 5 μM Veliparib. Cultures were immunolabeled for Neuro filament-H (NF-H) and counterstained with Hoescht. d. Schematic showing that motor neuron loss induced by virally expressed TDP-43 in spinal cord cultures and that this loss is suppressed by the PARP-1/2 inhibitor Veliparib

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