Table 2.
Increased and downregulated astrocyte proteins that affect synapse number.
| Astrocyte protein | Astrocyte expression changes in AD | Effect on synapses in AD | Model | References |
|---|---|---|---|---|
| Increased expression in AD | ||||
| ATP | Release increased by Aβ | Protects against Aβ mediated spine loss | Primary mouse astrocytes from 1-day-old ICR mice, human U373 astrocyte, and primary rat hippocampal cell cultures, strain unknown, treated with Aβ | (Jung et al., 2012) |
| LCN2 | Brain-region specific upregulation | – | Post-mortem AD patient brain tissue | (Dekens et al., 2017) |
| Increased expression after Aβ treatment; | – | Primary cortex cultures of astrocytes from 5 to 7-day-old Wistar Han rats, treated with Aβ, sex unknown | (Mesquita et al., 2014) | |
| Increased expression after Aβ treatment; | Reduced total spine number, specifically affecting thin and mushroom spines | Primary cortex of hippocampal astrocyte culture from 0 to 3-day-old C57BL/6 pups and organotypic hippocampal slice cultures from 6 to 8-day-old mice, treated with Aβ | (Maysinger et al., 2017) | |
| CaN | Increased expression in reactive astrocytes. | – | 3–18-month-old male APP/PS1 mice, on a C57CBL/6J background | (Norris, 2005) |
| – | Inhibition increases levels of synaptophysin and PSD-95 | 10-month-old male and female AβPP/PS1 mice, on a B6C3 background | (Hong et al., 2010) | |
| P2Y1R | Increased in AD patients and AD mouse model. | Blocking P2Y2R activity attenuates AD induced loss of synapses | Post-mortem brain tissue and aged (8+-month-old for expression, and 11-month-old for synapse analysis) APP/PS1 mice, on a C57BL/6J background, sex unknown | (Reichenbach et al., 2018) |
| CIP2A | Upregulated expression in reactive astrocytes (1) | CIP2A induced astrocyte reactivity decreased PSD-95, synapsin-1 (2) and synaptophysin levels and CIP2A overexpression in astrocytes resulted in decreased number of dendritic spines in hippocampus (3) | (1) Post-mortem AD brain tissue and 9-month-old male 3xTg mice, unknown background (2) Primary rat cortical astrocyte and neuron culture from new-born Sprague-Dawley rats (3) 9-month-old male 3xTg mice, unknown background | (Shentu et al., 2019) |
| TRPA1 | Increased expression in hippocampus | – | 8-month-old APP/PS1 mice, on a C57BL background, sex unknown | (Lee et al., 2016) |
| – | Inhibition of TRPA1 prevents astrocytic withdrawal from spines and preserves spine density and morphology. | 1–3-month-old male and female APP/PS1-21 mice, on a C57BL6/J background | (Paumier et al., 2021) | |
| Decreased expression in AD | ||||
| BDNF | Decreased levels in AD | Decreased spine density and PSD-95 and synaptophysin expression | Hippocampus of 5-monht-old Tg2576, on a B6SJL background, sex unknown | (Hongpaisan et al., 2011) |
| Primary hippocampal astrocyte-neuron co-cultures from 1 to 3-day-old BDNF KO mice 8-month-old 5xFAD male mice crossed with BDNF KO mice or pGFAP-BDNF mice, background unknown | (Du Z. et al., 2021) | |||
| TGF-β1 | Decreased expression by Aβ | Increased Aβ mediated spine loss. Treatment with TGF-β1 prevents Aβ induced synapse loss. | Primary mouse hippocampal cultures from 1 to 2-day-old Swiss mice, adult primary human astrocyte cultures and 3-month-old male Swiss mice | (Pereira Diniz et al., 2017) |
| Unknown expression change in AD | ||||
| 5-HT2 receptor | ?* | When active prevents loss of Synaptophysin and MAP2 via reduction of astrocyte Aβ production | Hippocampal neuron cultures treated with ACM from FLX treated primary cortical astrocyte cultures from 1-day-old APP/PS1 mice, sex unknown | (Qiao et al., 2016) |
| FOXO3 | ?* | FOXO3 KO results in a loss of synaptophysin and PSD-95 | Cortex of 3.5-month-old male and female 5xFAD mice, on a C57BL/6J background | (Du S. et al., 2021) |
*Unknown expression change in AD.