Characterization of the
microglial capacity to phagocytize LPNPs
in the rat hypothalamus. (A, B) Small (A) or large (B) number of LPNP-Au-containing
phagolysosomes (red) accumulate in ionized calcium binding adaptor
molecule 1-immunoreactive (Iba1-ir, green) microglia. (C) 3D reconstruction
of LPNP-Au-555-containing phagolysosomes (yellow) and Iba1-ir microglial
soma (blue) based on panels (B1, B2) for the volume calculation. (D,
E) Quantification of the total number and volume of the LPNP-Au-555-containing
phagolysosomes in microglial cells. (F) An illustration of a LPNP-Au
by electron microscopy shows a LPNP that contains several 10 nm Au
particles (pointed by a white arrowhead). (G–I) Characterization
of LPNP-Au nanoparticle accumulation in phagolysosomes by electron
microscopy. (G) Microglia are recognized with their densely packed
heterochromatin-containing nuclei (asterisk in panel G); four Au-containing
phagolysosomes in the microglia distal to the nucleus indicated by
the red arrow in panel (G) are shown in high magnification in panel
(H); the orange-dotted lines in panel (G) frame the area covered by
the microglial soma. (I) One of the 10 nm Au particle-containing phagolysosomes
also contains a 15 nm Au particle derived from immunogold labeling
for the lysosome marker LAMP1 (pointed by a red arrowhead). (J) Diameter
of the Au-containing phagolysosomes in microglia. (K–N) The
localization of the siRNA-FAM (green) in the cytosolic compartments
of microglial cells with 0.5 h (K, L) or 6 h (M, N) treatment. The
lysosomes in the cytosolic compartments are visualized with LysoTracker
(red). Higher magnification of the cells pointed by the white arrows
in panels (K) or (M) was illustrated in panels (L) or (N). (O) Ratio
between the area of coverage of the extra-Lyso siRNA-FAM fluorescence
signal and the LysoTracker fluorescence signal in the BV2 cells with
0.5 or 6 h treatment. All the results were presented as means ±
SD. The data were analyzed using Student’s t test in panel (O). Scale bar: 10 μm in panels (A–C),
100 nm in panel (F), 1 μm in panel (G), 200 nm in panel (H),
100 nm in panel (I), 15 μm in panels (K, M), and 5 μm
in panels (L, N).