Neuroprotection mediates through oestrogen receptor alpha in astrocytes
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Transcript of Neuroprotection mediates through oestrogen receptor alpha in astrocytes
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
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.”
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
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
ER-α is specifically deleted from either neurons or astrocytes in the respective neuronal-ERα-CKO or astrocyte-ERα-CKO models.
RESULTS
METHODSTreatments
EAE
Normal
Immunization ☹
Erα ligand
Vehicle
Erα ligand
Vehicle
ER-α expression is necessary in astrocytes, but not in neurons, for clinical disease protection.
RESULTS
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
ER-α expression is necessary in astrocytes, but not in neurons, to prevent macrophage and T-cell inflammation in the CNS..
RESULTS
ER-α expression is necessary in astrocytes, but not in neurons, to attenuate axonal loss and gliosis.
RESULTS
Demyelination
Axon number
Astrogliosis
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.