Imperial College London
Portrait Picture

ProfessorMagdalenaSastre

Faculty of Medicine, Department of Brain Sciences

Professor in Molecular Neuroscience
 
 
 
//

Contact

 

+44 (0)20 7594 6673m.sastre

 
 
//

Location

 

406Burlington DanesHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Sidoryk-Wegrzynowicz:2017:10.1186/s40478-017-0478-9,
author = {Sidoryk-Wegrzynowicz, M and Gerber, YN and Ries, M and Sastre, M and Tolkovsky, AM and Spillantini, MG},
doi = {10.1186/s40478-017-0478-9},
journal = {Acta Neuropathologica Communications},
title = {Astrocytes in mouse models of tauopathies acquire early deficits and lose neurosupportive functions},
url = {http://dx.doi.org/10.1186/s40478-017-0478-9},
volume = {5},
year = {2017}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Microtubule-associated protein tau aggregates constitute the characteristic neuropathological features of severalneurodegenerative diseases grouped under the name of tauopathies. It is now clear that the process of tauaggregation is associated with neurodegeneration. Several transgenic tau mouse models have been developed wheretau progressively aggregates, causing neuronal death. Previously we have shown that transplantation of astrocytes inP301S tau transgenic mice rescues cortical neuron death, implying that the endogenous astrocytes are deficient insurvival support. We now show that the gliosis markers Glial fibrillary acidic protein (GFAP) and S100 calcium-bindingprotein B (S100β) are elevated in brains from P301S tau mice compared to control C57Bl/6 mice whereas theexpression of proteins involved in glutamine/glutamate metabolism are reduced, pointing to a functional deficit. Totest whether astrocytes from P301S mice are intrinsically deficient, we co-cultured astrocytes and neurons from controland P301S mice. Significantly more C57-derived and P301S-derived neurons survived when cells were cultured withC57-derived astrocytes or astrocyte conditioned medium (C57ACM) than with P301S-derived astrocytes or astrocyteconditioned medium (P301SACM), or ACM from P301L tau mice, where the transgene is also specifically expressed inneurons. The astrocytic alterations developed in mice during the first postnatal week of life. In addition, P301SACMsignificantly decreased presynaptic (synaptophysin, SNP) and postsynaptic (postsynaptic density protein 95, PSD95)protein expression in cortical neuron cultures whereas C57ACM enhanced these markers. Since thrombospondin 1(TSP-1) is a major survival and synaptogenic factor, we examined whether TSP-1 is deficient in P301S mouse brains andACM. Significantly less TSP-1 was expressed in the brains of P301S tau mice or produced by P301S-derived astrocytes,whereas supplementation of P301SACM with TSP-1 increased its neurosupportiv
AU  - Sidoryk-Wegrzynowicz,M
AU  - Gerber,YN
AU  - Ries,M
AU  - Sastre,M
AU  - Tolkovsky,AM
AU  - Spillantini,MG
DO  - 10.1186/s40478-017-0478-9
PY  - 2017///
SN  - 2051-5960
TI  - Astrocytes in mouse models of tauopathies acquire early deficits and lose neurosupportive functions
T2  - Acta Neuropathologica Communications
UR  - http://dx.doi.org/10.1186/s40478-017-0478-9
UR  - http://hdl.handle.net/10044/1/52742
VL  - 5
ER  -
Download