Astrocytes: Lessons Learned from the Cuprizone Model
Abstract
:1. Introduction
2. Glia Cells
3. Multiple Sclerosis Animal Models
4. Astrocytes and the Cuprizone Model
5. Conclusions
Citation | Main Finding(s) |
---|---|
[46] | Astrocyte proliferation via 3H-thymidine labelling |
[48] | Astrocyte activation, demonstrated by IHC and ISH |
[56] | IGF-1 is expressed by astrocytes and the receptor by oligodendrocytes |
[92] | Altered astrocytic glutathione-S-transferase isoform expression during demyelination |
[93] | Altered astrocytic glutathione-S-transferase isoform expression during remyelination |
[47] | Astrogliosis promptly follows microgliosis during demyelination |
[59] | Amelioration of cuprizone-induced pathology ameliorates the extent of astrocyte activation; IFN-γ overexpression, driven by the MBP reporter |
[94] | Amelioration of cuprizone-induced pathology ameliorates the extent of astrocyte activation; MIP-1alpha deficiency |
[60] | IL1β-deficient mice have lower IGF-1 levels during the remyelination phase |
[95] | Astrocytes express MHC class I and II |
[96] | Transgenic mice that overexpress PDGF-A in astrocytes have increased OPC numbers |
[61] | Peripheral benzodiazepine receptor is expressed by astrocytes and microglia |
[97] | Osteopontin is expressed by astrocytes and microglia |
[98] | Notch1 is expressed by various cell types, including astrocytes, within remyelinating lesions |
[84] | Lymphotoxin-alpha is expressed by astrocytes and exacerbates demyelination |
[99] | Metallothionein-I and –II are expressed by astrocytes |
[100] | Different pathologies, including axonal injury and astrocyte activation, are more pronounced in aged versus young mice during demyelination |
[101] | Complement regulatory protein Crry overexpression in astrocytes protects against demyelination |
[102] | The acyl-CoA synthetase, lipidosin, is expressed by astrocytes |
[40] | Platelet-derived growth factor-A overexpression in astrocytes supports remyelination |
[103] | Metallothionein I/II are expressed by astrocytes |
[39] | Extent of astrocytosis differs between demyelinated white and grey matter areas |
[104] | Cortical demyelination, but not astrogliosis per se, is associated with accelerated cortical spreading depression |
[105] | Astrocyte progenitor cells accumulate in cuprizone lesions |
[106] | ADAM12 is expressed by astrocytes |
[107] | Increased numbers of astrocytes in vivo within the subventricular zone during demyelination, and numbers were decreased by intraventricular Noggin infusion |
[108] | CXCL12 is expressed by astrocytes and microglia |
[109] | Cx47 is expressed by astrocytes |
[110] | Glial isoform of APP is expressed by astrocytes |
[111] | C3a and C5a overexpression exacerbates demyelination and delays remyelination |
[112] | IV-injected human-embryonic-stem-cell-derived neural precursor cells into mice express GFAP to a limited extent |
[85] | IκB kinase 2 depletion in astrocytes ameliorates demyelination |
[113] | Smad1, Smad5, and Smad8, intracellular effectors of the bone morphogenetic protein (BMP) family of proteins, are active in oligodendrocytes and a subset of astrocytes |
[65] | TSPO is expressed by astrocytes and microglia |
[114] | COX-1 is expressed by astrocytes and microglia |
[86,115] | Galectin-1 and -3 are expressed by astrocytes and microglia; galectin-3-deficient mice show impaired remyelination |
[116] | Serine palmitoyltransferase, the rate-limiting enzyme for ceramide de novo biosynthesis, is expressed by astrocytes |
[117] | FABP7 is expressed by astrocytes |
[118] | IGF1 is expressed by astrocytes |
[119] | MMP3 and MMP9 are expressed by astrocytes |
[52] | RXRβ is expressed by astrocytes |
[120] | Carbonic Anhydrase II is expressed by astrocytes |
[121] | Act1-deletion in astrocytes ameliorates demyelination |
[122] | p65 is active in astrocytes |
[87] | TNFR1 and TNFR2 are expressed by astrocytes and microglia; CXCL12 is expressed by astrocytes, which promotes OPC proliferation and differentiation |
[72] | In contrast to microgliosis, astrocytosis persists during de- and remyelination. Astrocyte reaction is characterized, among others features, by early astrocyte proliferation and increased expression of GFAP, vimentin, and fibronectin. Furthermore, there is an elaboration of a dense network of processes |
[73] | Astrocyte ablation results in impaired remyelination |
[123] | IGF1 infusions can decrease astrocyte numbers during remyelination |
[124] | Glutamate-aspartate transporter is expressed by astrocytes |
[125] | Receptor protein tyrosine phosphatase β is expressed in astrocytes |
[126] | IL6 is expressed by astrocytes |
[88] | mGluR1, mGluR5, and BDNF are expressed by astrocytes; astrocyte-derived BDNF promotes recovery from cuprizone-induced demyelination |
[77] | CXCL10 is mainly expressed by astrocytes |
[127] | Oncostatin M receptor is expressed by astrocytes and microglia; OSMR deficiency aggravates demyelination; CNS-targeted OSM treatment ameliorates demyelination |
[128] | Erk is especially activated in astrocytes and promotes demyelination |
[129] | Transgenic mice that overexpress IL6 in astrocytes show reduced glia activation, axonal injury, and OPC recruitment |
[82] | Transient Receptor Potential Ankyrin 1 (TRPA1) is expressed in astrocytes; TRPA1 deficiency significantly attenuated cuprizone-induced demyelination by reducing the apoptosis of mature oligodendrocytes |
[130] | Activation of the astrocytic Nrf2/ARE system ameliorates demyelination |
[131] | Transgenic mice that overexpress IL-17A in astrocytes show aggravation of demyelination |
[132] | Transglutaminase 2 is expressed by astrocytes |
[133] | Transgenic mice that overexpress IL6 in astrocytes show amelioration in the cuprizone-induced pathologies |
[134] | S1P receptor 1 is expressed by astrocytes, and its modulation ameliorates demyelination |
[135] | Astrocytes show NF-κB activation |
[136] | Gli1 is expressed by astrocytes after chronic, but not acute, demyelination |
[137] | Cuprizone induces astrocyte atrophy in the rat |
[138] | Metallothionein I/II and Megalin are expressed by astrocytes |
[139] | Sox10 converts astrocytes into oligodendrocyte-like cells |
[140] | Transplanted astrocytes convert into oligodendrocyte-like cells |
[35] | DDIT3 is expressed by oligodendrocytes and astrocytes |
[141] | Sox2 converts astrocytes into oligodendrocyte-like cells |
[91] | Astrocyte ablation augments remyelination after chronic demyelination |
[63] | TSPO is expressed by microglia and astrocytes |
[142] | Transferrin can be incorporated by all glial cells among astrocytes |
[143] | Overexpression of GFAP reduces cuprizone-induced apoptosis, demyelination, and acute axonal damage |
[144] | Mesenchymal stem cells reduce astogliosis and microgliosis |
[145] | CD38 is expressed by astrocytes and microglia; CD38 ameliorates demyelination |
[146] | Astrocytes express NRF2, HO-1, and PI3K; Ginkgolide K augments the expression of these proteins |
[147] | Astrocytes express SOX2, CNTF, IGF2, and BDNF |
[148] | Astrocyte-specific deletion of Transient receptor potential ankyrin 1 delays demyelination |
[149] | PAR1 knock-out mice demonstrate skewing of reactive astrocyte signatures towards a pro-repair phenotype |
[150] | Astrocytes express BDNF and GDNF; Ginkgolide B augments the expression of these proteins |
[151] | Deletion of astrocytic Cav1.2 channels leads to reduced astrocytosis, microgliosis, ameliorates inflammation, and promotes remyelination |
[152] | P2x7 receptors are expressed by astrocytes and microglia; demyelination is ameliorated in P2x7-deficient mice |
[153] | Induced neural stem cells ameliorate astrocytosis |
[154] | CD44 is expressed by astrocytes and microglia; Cd44 deficiency does not ameliorate cuprizone-induced pathology |
[155] | Some astrocytes show oxidative damage to DNA (id est, 8-OHdG+) |
[156] | SIRT1 is expressed by astrocytes, microglia, and mature oligodendrocytes |
[157] | Mesenchymal stem cell transplantation ameliorates astrocytosis |
[158] | AQP4 is expressed in astrocyte endfeet; polarized expression is reduced after demyelination |
[159] | Astrocytes phagocytose myelin; astrocytes express BDNF, CTNF, Nestin, SOX2, Notch, and ß-catenin; expression profiles are regulated by ethyl pyruvate |
[160] | Astrocytes express NgR1, SPARC, and Hevin; astrocytic NgR1 sublocalization alters during demyelination; |
[161] | Astrocytes express C3; TIC knock-outs show reduced C3 expression |
[162] | Aastrocyte participation in the tripartite synapse during demyelination |
[163] | mGluR5 is expressed by astrocytes and orchestrates remyelination |
[164] | EBI2 receptor is expressed in astrocytes and microglia |
[165] | Astrocytes express TrkB, CTR1, ATP7A, and ATP7B; demyelination is ameliorated in mice lacking astrocytic TrkB expression |
[166] | Fth deletion in Glast1/EAAT1-positive astrocytes inhibits remyelination |
[167] | EAAT2 is expressed by astrocytes |
[168] | Astrocytes express S100B, GFAP, vimentin, LCN2, and ALDH1L1 |
[83] | LCN2 is expressed by astrocytes; oligodendrocyte loss is more severe in Lcn2-/- animals |
[169] | Ongoing astrocytosis weeks after completion of remyelination |
[170] | C3d, S100a10, Stat3, and Timp1 are expressed by astrocytes |
[171] | C3d and S100a10 are expressed by astrocytes; Bu Shen Yi Sui capsules promote an A2 phenotype |
[172] | Combined mesenchymal stem cell transplantation and astrocyte ablation support remyelination |
[173] | Cuprizone intoxication induces astrocyte endfeet sweelings |
[174] | Astrocytes express TRAP1; β-hydroxybutyrate downregulates the expression of this protein |
[71] | High-resolution, single-nucleus RNA sequencing (snRNA-seq) analysis of gene expression changes across various brain cells, including astrocytes |
[175] | Bone Marrow Mesenchymal Stem Cells reduce astrocytosis |
[176] | Astrocytes express HNK-1-O-Man+ PTPRZ |
[177] | A1 versus A2 astrocyte expression profiling |
[178] | The AQP4 inhibitor TGN020 ameliorates astrocyte and microglia activation |
[76] | Astrocytic transcriptome signature investigated via ribosomal tagging |
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Kipp, M. Astrocytes: Lessons Learned from the Cuprizone Model. Int. J. Mol. Sci. 2023, 24, 16420. https://doi.org/10.3390/ijms242216420
Kipp M. Astrocytes: Lessons Learned from the Cuprizone Model. International Journal of Molecular Sciences. 2023; 24(22):16420. https://doi.org/10.3390/ijms242216420
Chicago/Turabian StyleKipp, Markus. 2023. "Astrocytes: Lessons Learned from the Cuprizone Model" International Journal of Molecular Sciences 24, no. 22: 16420. https://doi.org/10.3390/ijms242216420
APA StyleKipp, M. (2023). Astrocytes: Lessons Learned from the Cuprizone Model. International Journal of Molecular Sciences, 24(22), 16420. https://doi.org/10.3390/ijms242216420