neuroprotection mediates through oestrogen receptor alpha in astrocytes
DESCRIPTION
Journal ClubTRANSCRIPT
![Page 1: Neuroprotection mediates through oestrogen receptor alpha in astrocytes](https://reader034.vdocuments.net/reader034/viewer/2022042602/557dd0a6d8b42ae4688b4d78/html5/thumbnails/1.jpg)
Neuroprotection mediated through Estrogen Receptor-alpha in astocytesRory D. Spence, Mary E. Hamby, Elizabeth Umeda, Noriko Itoh, Sienmi Du, Amy J. Wisdom, Yuan
Cao,!Galyna Bondar, Jeannie Lam, Yan Ao, Francisco Sandoval, Silvie Suriany, Michael V. Sofroniew,!
and Rhonda R. Voskuhl.
PNAS, April 2011
15 | 05 | 2013
![Page 2: Neuroprotection mediates through oestrogen receptor alpha in astrocytes](https://reader034.vdocuments.net/reader034/viewer/2022042602/557dd0a6d8b42ae4688b4d78/html5/thumbnails/2.jpg)
INTRODUCTION
❶ Demographics
❸ Estrogen receptor-alpha (ER-α)
❷ Estrogen and hormone replacement therapy
HYPOTHESIS !“Central nervous system neuroprotective effects
of estrogen mediated through ERα in vivo are
effectuated via expression of ERα in either
neurons or astrocytes.”
![Page 3: Neuroprotection mediates through oestrogen receptor alpha in astrocytes](https://reader034.vdocuments.net/reader034/viewer/2022042602/557dd0a6d8b42ae4688b4d78/html5/thumbnails/3.jpg)
METHODSConditional gene KO in gonadectomized mice
Cell type specific promoter Lox-p flanked target gene
Gene of interest is deleted
in specific cell type only
![Page 4: Neuroprotection mediates through oestrogen receptor alpha in astrocytes](https://reader034.vdocuments.net/reader034/viewer/2022042602/557dd0a6d8b42ae4688b4d78/html5/thumbnails/4.jpg)
METHODS
rNSE-Cre
mGFAP-Cre Astrocyte-ERα-CKO (mGFAP Cre+/ERαflox/flox)
Neuron-ERα-CKO (rNSE Cre+/ERαflox/flox)
ERαflox/flox
ERαflox/flox
Conditional gene KO in gonadectomized mice
![Page 5: Neuroprotection mediates through oestrogen receptor alpha in astrocytes](https://reader034.vdocuments.net/reader034/viewer/2022042602/557dd0a6d8b42ae4688b4d78/html5/thumbnails/5.jpg)
ER-α is specifically deleted from either neurons or astrocytes in the respective neuronal-ERα-CKO or astrocyte-ERα-CKO models.
RESULTS
![Page 6: Neuroprotection mediates through oestrogen receptor alpha in astrocytes](https://reader034.vdocuments.net/reader034/viewer/2022042602/557dd0a6d8b42ae4688b4d78/html5/thumbnails/6.jpg)
METHODSTreatments
EAE
Normal
Immunization ☹
Erα ligand
Vehicle
Erα ligand
Vehicle
![Page 7: Neuroprotection mediates through oestrogen receptor alpha in astrocytes](https://reader034.vdocuments.net/reader034/viewer/2022042602/557dd0a6d8b42ae4688b4d78/html5/thumbnails/7.jpg)
ER-α expression is necessary in astrocytes, but not in neurons, for clinical disease protection.
RESULTS
![Page 8: Neuroprotection mediates through oestrogen receptor alpha in astrocytes](https://reader034.vdocuments.net/reader034/viewer/2022042602/557dd0a6d8b42ae4688b4d78/html5/thumbnails/8.jpg)
ER-α expression is necessary in astrocytes, but not in neurons, to prevent macrophage and T-cell inflammation in the CNS.
RESULTS
Associated with machophages
Associated with microglia
T-cells
![Page 9: Neuroprotection mediates through oestrogen receptor alpha in astrocytes](https://reader034.vdocuments.net/reader034/viewer/2022042602/557dd0a6d8b42ae4688b4d78/html5/thumbnails/9.jpg)
ER-α expression is necessary in astrocytes, but not in neurons, to prevent macrophage and T-cell inflammation in the CNS..
RESULTS
![Page 10: Neuroprotection mediates through oestrogen receptor alpha in astrocytes](https://reader034.vdocuments.net/reader034/viewer/2022042602/557dd0a6d8b42ae4688b4d78/html5/thumbnails/10.jpg)
ER-α expression is necessary in astrocytes, but not in neurons, to attenuate axonal loss and gliosis.
RESULTS
Demyelination
Axon number
Astrogliosis
![Page 11: Neuroprotection mediates through oestrogen receptor alpha in astrocytes](https://reader034.vdocuments.net/reader034/viewer/2022042602/557dd0a6d8b42ae4688b4d78/html5/thumbnails/11.jpg)
CONCLUSIONER-α expression is necessary in astrocytes, but not in neurons…
❶ for clinical disease protection.
❷ to prevent macrophage and T-cell inflammation in the CNS.
❸ to attenuate axonal loss and gliosis.
![Page 12: Neuroprotection mediates through oestrogen receptor alpha in astrocytes](https://reader034.vdocuments.net/reader034/viewer/2022042602/557dd0a6d8b42ae4688b4d78/html5/thumbnails/12.jpg)