. Author manuscript; available in PMC: 2021 Jul 1.

Published in final edited form as: Ageing Res Rev. 2021 Mar 31;68:101335. doi: 10.1016/j.arr.2021.101335

Table 1.

Astrocyte targeting strategies in intact animal models of AD-like pathology.

Molecular target	Targeting method	Bio/behavioral Effects

Calcineurin/NFAT	AAV-GFa2 delivery of VIVIT to hippocampus of APP/PS1 mice	Reduced frequency of large, reactive astrocytes; reduced Iba1 immunolabeling and protein levels; reduced Aβ pathology; reduced BACE1 expression; increased synaptic strength and LTP; improved cognitive status (Furman et al., 2012)
	AAV-Gfa2 delivery of VIVIT to hippocampus of 5xFAD mice	Improved cognitive status; reduced GFAP levels; reduced Aβ pathology; reduced frequency and duration of spontaneous glutamate transients; increased Glt-1 levels; reduced neurite atrophy; improved synaptic strength; reduced frequency of spontaneous synaptic currents; restoration of AMPA/NMDA balance (Sompol et al., 2017)
	Gfa-ΔCN (activated calcineurin) overexpressing mice (dox sensitive) crossed with APP/PS1 mice.	Reduced Aβ; reduced GFAP, TNFα and Cd11b1 mRNA levels; improved cognitive status (Fernandez et al., 2012)
JAK/STAT	AAV-Gfa delivery of SOCS3 into the hippocampus of APP/PS1 mice	Normalized astrocytic transcriptome; reduced GFAP/Vimentin immunoreactivity; reduced Aβ pathology improved cognitive status (Ceyzeriat et al., 2018)
	AAV-Gfa delivery of SOCS3 into the hippocampus of 3xTg mice	Improved synaptic strength and LTP (Ceyzeriat et al., 2018); reduced GFAP protein levels and immunoreactivity; reduced anxiety (Geuillemaud et al., 2020)
	Lentivirus delivery of SOC3 into hippocampus of 3xTg	Reduced number of GFAP + astrocytes and reduced GFAP immunoreactivity (Haim et al., 2015)
	Conditional knock-out of Stat3 in astrocytes of APP/PS1 mice	Increased astrocyte volume around Aβ plaques; increased microglia branching around plaques; reduced Aβ pathology and microglial-mediated internalization/degradation of Aβ; reduced levels of inflammatory cytokines; reduced neurite atrophy near Aβ plaques; reduced spontaneous Ca²⁺ transients in astrocytes and neurons; improved cognitive status (Reichenbach et al., 2019)
EAAT2/Glt-1	Gfa-human EAAT2 mice crossed with J20 mice.	Improved glutamate uptake; improved cognitive status; increased synapsin levels; reduced Aβ pathology; improved survival (Takahashi et al., 2015)
Connexins	Gfa-Cx43 knock-out mice crossed with APP/PS1 mice	Reduced unapposed hemichannel activity; reduced astrocytic Ca²⁺ levels; reduced release of ATP and glutamate; improved neuronal viability; reduced Aβ pathology (Yi et al., 2016); improved cognitive status; reduced number of GFAP + astrocytes; improved LTP; increased dendritic spine density
GFAP/vimentin	GFAP + vimentin knock-out mice crossed with	Increased Aβ pathology; increased neuritic dystrophy; reduced astrocyte coverage of Aβ plaques; increased microglia coverage of plaques (Kraft et al., 2013); increase in in neuroinflammatory genes; increased neuronal support genes; no effect on Aβ pathology (Kamphuis et al., 2015)