HIV-1 Tat-Induced Microgliosis and Synaptic Damage via Interactions between Peripheral and Central Myeloid Cells
Figure 10
Tat alters ultrastructural relationships between polymorphonuclear granulocytes, microglia and neuronal elements including synapses in the cerebral cortex of CX3CR1+/− mice.
This is a montage of electron micrographs 24 hrs (Panels A–D) or 7 d (Panels E, F) after Tat injection (n = 3 independent replicates). Panels A and B show a polymorphonuclear granulocyte (pmn) cell body in apposition to a microglial process. Panel B presents a higher resolution view of the boxed region in Panel A Two processes arising from the degenerating polymorphonuclear granulocyte (arrows) surround an Iba-1 immunopositive microglial process (m+) with a cellular inclusion (in). Panel C presents another example of microglial process with a cellular inclusion. In both Panels B and C, the cellular inclusion appears as engulfed material from degenerating neurons. In Panel D, a microglial process contains three cellular inclusions resembling profiles of dendrites (“d”). Direct contacts with other synaptic elements including dendritic spines (s) and axon terminals (t) are also observed. Panel E shows a microglial process displaying a cellular inclusion resembling an axon terminal (“t”; arrows), as well as cellular inclusions resembling a dendrite, suggesting their phagocytic engulfment by microglia after HIV infection. Panel F presents a higher resolution view of the boxed region in Panel E. a, astrocytic process; d, dendrite; ma, myelinated axon; n, nucleus; N, neuron; *, extracellular space; scale bars, 1 µm (Panel A) and 0.5 µm (Panels C–E).