Figure 3. HIV-1 Tat induces endoplasmic reticulum neuropathologic changes in cortical neurons.

A–L, The following symbols are used throughout the montage: m, mitochondria; n, nucleus; black arrows, ER; white arrows, ribosomes. A, Control neurons displayed classic rough ER morphology with ribosomes contiguous with the rough ER membrane. B, Cortical neurons treated with 8 nM Tat demonstrated a dilation of ER and a dissociation of ribosomes. C, An untreated cortical neuron displayed normal morphology. D, A magnified image of the untreated cortical neuron in C. E, Cortical neuron treated with 8 nM Tat for 15 minutes. F, A magnified image of the treated [8 nM Tat] cortical neuron. G, Cortical neuron treated with [8 nM] Tat for 15 minutes displayed dilated ER. H, Magnified image of treated neuron in G. The dilated ER at this level of magnification was highly prominent. I, Cortical neurons pretreated with an antagonist concentration [20 µM] of ryanodine for 30 min before [8 nM] of Tat treatment displayed none of the pathology demonstrated in previous images. J, Cortical neurons pretreated with the RyR antagonist [25 µM] dantrolene for 30 min before [8 nM] of Tat treatment had similar morphologies to those that received [20 µM] ryanodine pretreatment. K, Cortical neurons pretreated with the IP₃ inhibitor [100 µM] TMB-8 for 1 hour before Tat [8 nM] treatment failed to attenuate the morphological pathology induced by Tat. L, Cortical neurons pretreated for 30 minutes with 2 µM MK-801 also failed to attenuate the pathology elicited by treatment of Tat [8 nM].