Oestradiol-induced synapse formation in the female hippocampus: roles of oestrogen receptor subtypes

TY - JOUR

T1 - Oestradiol-induced synapse formation in the female hippocampus: roles of oestrogen receptor subtypes

AU - Zhou, L

AU - Fester, L

AU - Haghshenas, S

AU - de Vrese, X

AU - von Hacht, R

AU - Gloger, S

AU - Brandt, N

AU - Bader, M

AU - Vollmer, G

AU - Rune, G M

N1 - © 2014 British Society for Neuroendocrinology.

PY - 2014/7/1

Y1 - 2014/7/1

N2 - During the oestrus cycle, varying spine synapse density correlates positively with varying local synthesis of oestradiol in the hippocampus. In this context, the roles of the oestrogen receptor (ER) subtypes ERα and β are not fully understood. In the present study, we used neonatal hippocampal slice cultures from female rats because these cultures synthesise oestradiol and express both receptor subtypes, and inhibition of oestradiol synthesis in these cultures results in spine synapse loss. Using electron microscopy, we tested the effects on spine synapse density in response to agonists of both ERα and ERβ. Application of agonists to the cultures had no effect. After inhibition of oestradiol synthesis, however, agonists of ERα induced spine synapse formation, whereas ERβ agonists led to a reduction in spine synapse density in the CA1 region of these cultures. Consistently, up-regulation of ERβ in the hippocampus of adult female aromatase-deficient mice is paralleled by hippocampus-specific spine synapse loss in this mutant. Finally, we found an increase in spine synapses in the adult female ERβ knockout mouse, but no effect in the adult female ERα knockout mouse. Our data suggest antagonistic roles of ERβ and ERα in spine synapse formation in the female hippocampus, which may contribute to oestrus cyclicity of spine synapse density in the hippocampus.

AB - During the oestrus cycle, varying spine synapse density correlates positively with varying local synthesis of oestradiol in the hippocampus. In this context, the roles of the oestrogen receptor (ER) subtypes ERα and β are not fully understood. In the present study, we used neonatal hippocampal slice cultures from female rats because these cultures synthesise oestradiol and express both receptor subtypes, and inhibition of oestradiol synthesis in these cultures results in spine synapse loss. Using electron microscopy, we tested the effects on spine synapse density in response to agonists of both ERα and ERβ. Application of agonists to the cultures had no effect. After inhibition of oestradiol synthesis, however, agonists of ERα induced spine synapse formation, whereas ERβ agonists led to a reduction in spine synapse density in the CA1 region of these cultures. Consistently, up-regulation of ERβ in the hippocampus of adult female aromatase-deficient mice is paralleled by hippocampus-specific spine synapse loss in this mutant. Finally, we found an increase in spine synapses in the adult female ERβ knockout mouse, but no effect in the adult female ERα knockout mouse. Our data suggest antagonistic roles of ERβ and ERα in spine synapse formation in the female hippocampus, which may contribute to oestrus cyclicity of spine synapse density in the hippocampus.

KW - Animals

KW - Aromatase

KW - Dendritic Spines

KW - Estradiol

KW - Estrogen Receptor alpha

KW - Estrogen Receptor beta

KW - Female

KW - Hippocampus

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Neurogenesis

KW - Organ Culture Techniques

KW - Rats

KW - Rats, Wistar

KW - Synapses

U2 - 10.1111/jne.12162

DO - 10.1111/jne.12162

M3 - SCORING: Journal article

C2 - 24779550

VL - 26

SP - 439

EP - 447

JO - J NEUROENDOCRINOL

JF - J NEUROENDOCRINOL

SN - 0953-8194

IS - 7

ER -