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. 2019 Jan 7;11(2):e9665. doi: 10.15252/emmm.201809665

Figure 4. Astrocyte‐specific Stat3 deletion increases microglial Aβ internalization and degradation, and reduces apoE expression, dystrophic neurites, and detrimental cytokines.

Figure 4

  • A
    Internalization of Aβ (stained with IC16 antibody or methoxy‐XO4) was assessed using an engulfment assay, in which glial and Aβ structures were surface‐rendered and Aβ volumes co‐localized with glial volumes were quantified. Scale bars, 10 μm.
  • B, C
    Microglia (left Y axes) from APP/PS1 mice internalized significantly more Aβ positive for IC16 or methoxy‐XO4 when Stat3 was deleted in astrocytes (*P < 0.05, Mann–Whitney test), whereas no changes were seen in astrocytes (right axes; APP/PS1‐Stat3WT, n = 8 (four females and four males) mice; APP/PS1‐Stat3KO, n = 11 (five females and six males) mice; age, 11 months; Mann–Whitney test).
  • D–H
    (D–F) Western blot quantification of protein levels of the Aβ‐degrading enzymes neprilysin/CD10 and CD36, as well as the Aβ‐binding apolipoprotein E (apoE), revealed a significantly increased expression of neprilysin and CD36 and a decreased expression of apoE (APP/PS1‐Stat3WT, n = 9 (five females and four males) mice; APP/PS1‐Stat3KO, n = 9 (five females and four males) mice; age, 11 months; *P < 0.05, Mann–Whitney test for all comparisons). (G) In contrast, TREM2 expression remained unchanged (APP/PS1‐Stat3WT, n = 8 (four females and four males) mice; APP/PS1‐Stat3KO, n = 7 (four females and three males) mice; age, 11 months; Mann–Whitney test). (H) Western blots for proteins analyzed in (D‐G).
Data information: Data are represented as mean ± SEM.Source data are available online for this figure.