Neuroprotection mediates through oestrogen receptor alpha in astrocytes
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
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.