ER-α expression is necessary in astrocytes, but not in neurons, for neuroprotection in an EAE model: 1) ER-α expression in astrocytes is required for clinical disease protection, while neuronal ER-α is not. 2) Astrocyte ER-α prevents macrophage and T-cell inflammation in the central nervous system. 3) Astrocyte ER-α attenuates axonal loss and gliosis, but neuronal ER-α does not.

1. Neuroprotection mediated through
Estrogen Receptor-alpha in astocytes
Rory 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

2. 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.”

3. METHODS
Conditional gene KO in gonadectomized mice
Cell type specific promoter Lox-p flanked target gene
Gene of interest is
deleted

4. 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

5. ER-α is specifically deleted from either neurons or astrocytes in the
respective neuronal-ERα-CKO or astrocyte-ERα-CKO models.
RESULTS

6. METHODS
Treatments
EAE
Normal
Immunization
☹
Erα ligand
Vehicle
Erα ligand
Vehicle

7. ER-α expression is necessary in astrocytes, but not in neurons, for
clinical disease protection.
RESULTS

8. 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

9. ER-α expression is necessary in astrocytes, but not in neurons, to
prevent macrophage and T-cell inflammation in the CNS..
RESULTS

10. ER-α expression is necessary in astrocytes, but not in neurons, to
attenuate axonal loss and gliosis.
RESULTS
Demyelination
Axon number
Astrogliosis

11. CONCLUSION
ER-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.