Fig. 2.
Pharmacological inhibitors selective for HDAC6 are protective in oxidatively stressed neurons, and promote neurite outgrowth in the presence of MAG. (A) Neuronal viability after treatment with homocysteic acid (HCA; 5 mM) with or without the pan-HDAC inhibitor TSA (0.66 μM), or the HDAC6-selective inhibitors MA-I (10 μM), and MA-II (10 μM) for 24 h. Viability was measured by using MTT assay. *, Significant protection compared to HCA treatment alone P < 0.001. §, Significant death compared to non-HCA control P < 0.001. (B) Live/Dead staining of treated rat primary cortical cultures. (C and D) Mean neurite length of cortical neurons measured after 24 h coculture with either R2 and R2M21+MAG cells in the presence or absence of the RhoA kinase Inhibitor (ROCKI), Y27632 (10 μM), the pan-HDAC inhibitor, TSA, or the HDAC6-selective inhibitors MA-I, and MA-II. Neurites were identified by neuron-specific β-III tubulin immunostaining and fluorescence microscopy (D), and measured by using Metamorph (C). Significant increase in neurite length relative to nontreated R2M21+MAG denoted by *, P < 0.05 or **, P < 0.001. Significant increase in neurite length relative to nontreated R2 denoted by §, P < 0.05.