TABLE 1.
Astrocyte‐specific interventions in APPswePS1dE9 mice
| Intervention | Target | Age | Sex | Background | Amyloid‐beta | Astrocytes | Microglia | Synaptic density | Memory | References |
|---|---|---|---|---|---|---|---|---|---|---|
| Gfap‐Cx43 −/− ‐APPswePS1dE9 a | Cx43 | 9 mo | F/M | – | – |
ATP release↓(ATPlite) Glutamate release↓ (CE‐LIF) GABA release↔ (CE‐LIF) |
– | Hip: RTN‐3 dystrophic neurites↓ (IHC) | – | Yi et al. (2016) |
| Gfap‐Cx43 −/− ‐APPswePS1dE9 b | Cx43 | 12 mo | – | BALB/c × C57BL/6NHsd × 129S7/SvEvBrd‐Hprtb‐m2 | Cx and Hip: Aβ number↔ (IHC, 6E10) |
Cx and Hip: GFAP number↓ (IHC) GFAP, GLAST and MEGF10↓ (qPCR and WB) |
– | Hip: Syn↔, PSD95↑ (WB) |
MWM↑ NOR↑ |
Ren, Zhang, and Wang (2018) |
|
GFAP‐iE3‐APPswePS1dE9 c Induced from birth |
ApoE | 6 mo1 or 9 mo2 | F/M | C57BL/6J × C3H/HeJ |
Cx: (in)soluble Aβ 40, Aβ 42 ↔ (ELISA) Cx: Aβ↔ (IHC) |
Cx and Hip: GFAP↓ 2 (IHC) | Cx and Hip: Iba1↔ 2 (IHC) | Cx: Syn↔ 2, PSD95↑ 2 (WB) | – | Liu et al. (2017) |
|
GFAP‐iE4‐APPswePS1dE9 c Induced from birth1,2 or 6 mo3 |
ApoE | 6 mo1, 9 mo2 or 9 mo3 | F/M | C57BL/6J × C3H/HeJ |
Cx: (in)soluble Aβ 40, Aβ 42 ↑ 1,2 (ELISA) Cx: (in)soluble Aβ 40, Aβ 42 ↔ 3 (ELISA) Cx and Hip: Aβ↑ 1,2 (IHC) Cx and Hip: Aβ↔ 3 (IHC) |
Cx and Hip: GFAP↑ 1,2 Cx and Hip: GFAP↔ 3 (IHC) |
Cx and Hip: Iba1↑ 2 (IHC) | Cx: Syn↔ 2, PSD95↔ (WB) | – | Liu et al. (2017) |
| AAV‐GFAP104‐DTR injection in hippocampus at 10–12 mo | Oxidative stress | 11–13 mo | F/M | C57BL/6J | – | Hip: GFAP intensity↑ (IHC) | Hip: Iba1 area↑ (IHC) | NeuN number↓ (IHC) | NPR↓ | Chun et al. (2020) |
| Intracerebroventricular injection of AAV‐GFAP‐CLU at 2 d | Clusterin | 8 mo | F/M | C57BL/6J × C3H/HeJ |
Cx: (in)soluble Aβ 40, Aβ 42 ↓ (ELISA) Cx and Hip: Aβ area↓ (IHC, X‐34) |
Cx: GFAP intensity↓ (IHC) Cx: Gfap↓ (qPCR) |
Cx: Iba1 intensity↓ (IHC) | Cx and Hip: Dystrophic neurites↓ (IHC) | – | Wojtas et al. (2020) |
| AAV‐gfaABC1D‐SOCS3 injection in hippocampus at 3–4 mo1 or injection at 15 mo2 | STAT3 | 9–10 mo1 or 16 mo2 | M | C57BL/6J × C3H/HeJ |
Hip: Aβ number↓ 1 (IHC, BAM10) Hip: Aβ 40, Aβ 42 ↔ 1 (ELISA) |
Hip: GFAP intensity↓ (IHC and WB) Vim intensity↓ 1 (IHC) |
Hip: Iba1 number per plaque↔ 1 (IHC) | – | MWM↑ 1 | Ceyzériat et al. (2018) |
|
Cx43‐STAT3 −/− ‐APPswePS1dE9 b Induced from 6 wk |
STAT3 | 8 mo | F/M | C57BL/6N |
Aβ area↓ (IHC, IC16, and ThS) Soluble Aβ 40, Aβ 42 ↓ (ELISA) |
Cx and Hip: GFAP area↔ (IHC) Peri‐plaque astroglial volume↑ |
Cx and Hip: Iba1 area↔ (IHC) Number of microglia branches and junctions↑ |
– | MWM↑ | Reichenbach et al. (2019) |
| APPswePS1dE9 c ‐GFAP −/− vimentin −/− | Intermediate filament proteins | 4 mo1, 8 mo2 and 12 mo3 | – | B6C3 × C57BL × 129SV × 129Ola |
Cx and Hip: Aβ area↑ 2,3 (IHC, HJ3.4 and X‐34) Cx: insoluble Aβ 40, Aβ 42 ↔ 1 Cx: Insoluble Aβ 40 ↑ 3 , Aβ 42 ↑ 2 (ELISA) |
Plaque‐astrocyte overlap↓ 3 GFAP number↔ 3 (IHC) |
Plaque‐microglia overlap↑ Iba1 number↑ 2 (IHC) Iba1↑ 3 (qPCR) |
ECx: RTN‐3↑ 3 (IHC) | – | Kraft et al. (2013) |
| APPswePS1dE9 c ‐GFAP −/− vimentin −/−1 and APPswePS1dE9 b ‐GFAP −/−2 | Intermediate filament protein(s) | 6 mo, 9 mo, and 15 mo | – | C57BL/6 × 129Sv × 129Ola | Aβ area↔ (IHC, 6E10) |
Plaque‐astrocyte overlap↓ Vim area↑ 2 (IHC) |
Iba1 number↔ (IHC) | – | – | Kamphuis et al. (2015) |
Abbreviations: General—Specified interventions or ages indicated with 1–3. When not indicated: same effect for all interventions or ages. When a specific group is not indicated: read‐out was not determined for that group; ↑, Increased or improved (Memory) compared to control of same age; ↓, decreased or impaired (Memory); ↔, no (significant) difference; –, not studied; d, day(s); mo, month(s); wk, week(s). Intervention and Target—Different APPswePS1dE9 strains indicated with a–c. aAPPswePS1dE9 mice, specific strain not indicated; bMMRRC Stock No: 34832‐JAX–C57BL/6J; cMMRRC Stock No: 34829‐JAX–C57BL/6J × C3H/HeJ. AAV, adeno‐associated virus‐based vectors; ApoE, apolipoprotein E; CLU, clusterin; Cx43, Connexin43; DTR, diphtheria toxin receptor; gfaABC1D, promoter to mediate astrocyte‐specific expression; GFAP, glial fibrillary acidic protein; iE3, inducible human ApoE3 expression; iE4, inducible human ApoE4 expression; SOCS3, suppressor of cytokine signaling 3; STAT3, signal transducer and activator of transcription 3. Age —at read‐out. Sex—Female (F), Male (M), or both (F/M). –, not indicated. Background: Genetic background of mice used in the study. x, Crossed with. Brain Regions—Cx, cortex; ECx, entorhinal cortex; Hip, hippocampus. Techniques—ATPlite, Luciferin‐luciferase bioluminescence assay; CE‐LIF, capillary electrophoresis with laser‐induced fluorescence; ELISA, enzyme‐linked immunosorbent assay; IHC, immunohistochemistry; MWM, Morris water maze; NOR, novel object recognition; NPR, novel place recognition; qPCR, quantitative polymerase chain reaction; WB, western blot. Genes, proteins, and transmitters—6E10, Aβ1–16 antibody; Aβ, amyloid‐beta; ATP, adenosine triphosphate; BAM10, Aβ1–40 antibody; GABA, gamma‐aminobutyric acid; GFAP, glial fibrillary acidic protein; GLAST, glutamate–aspartate transporter; HJ3.4, Aβ1–13 antibody; Iba1, ionized calcium‐binding adapter molecule 1; IC16, Aβ1‐16 antibody; MEGF10, multiple EGF‐like domains 10; PSD95, postsynaptic density protein 95; RTN‐3, reticulon‐3, marker of neuritic dystrophy; Syn, synaptophysin; ThS, thioflavin‐S; Vim, vimentin; X‐34 dye, fluorescent amyloid‐specific dye.