Androgens increase spine synapse density in the CA1 hippocampal subfield of ovariectomized female rats
Androgens increase spine synapse density in the CA1 hippocampal subfield of ovariectomized female rats
复制标题
DOI：
10.1523/jneurosci.4516-03.2004
复制
发表时间：
2004-01-14
影响因子：
5.3
通讯作者：
MacLusky, NJ
中科院分区：
文献类型：
--
作者：
Leranth, C;Hajszan, T;MacLusky, NJ
研究了雄激素对去卵巢（OVX）成年雌性大鼠海马CA1区锥体神经元棘突触密度的影响。用丙酸睾酮（TP； 500杯/天，s.c, 2 d）治疗OVX大鼠，脊柱突触密度显著增加(从OVX大鼠的0.661 +/- 0.016脊柱突触/妈妈（3)到TP治疗后的1.081 +/- 0.018脊柱突触/妈妈(3)）。在使用非芳香化雄激素二氢睾酮（DHT； 500马克杯/天，s.c， 2天）治疗后，OVX动物的突触密度增加较小，但仍具有统计学意义（0.955 +/- 0.029脊柱突触/母亲(3)）。在类固醇注射前1小时给予1mg来曲唑（一种强效的非甾体芳香酶抑制剂），几乎完全阻断了突触对睾酮的反应，导致平均突触密度（0.723 +/- 0.003个脊柱突触/母亲）仅略高于OVX对照大鼠。相比之下，对DHT的反应不受来曲唑预处理的影响。这些数据表明，雌性生殖周期中的雄激素分泌可能有助于海马突触密度的周期性变化。他们还指出，在逆转卵巢功能丧失后海马CA1脊柱突触的衰退方面，雄激素治疗可能与雌激素替代一样有效。然而，雄激素诱导海马突触形成并不完全通过脑内雌激素生物合成介导，因为芳香酶非依赖性机制也显著影响CA1脊柱突触密度。
The effects of androgen on the density of spine synapses on pyramidal neurons in the CA1 area of the hippocampus were studied in ovariectomized (OVX) adult female rats. Treatment of OVX rats with testosterone propionate (TP; 500 mug/d, s.c., 2 d) significantly increased spine synapse density (from 0.661 +/- 0.016 spine synapse/mum(3) in OVX rats to 1.081 +/- 0.018 spine synapse/mum(3) after TP treatment). A smaller, but still statistically significant, increase in synapse density (0.955 +/- 0.029 spine synapse/mum(3)) was observed in OVX animals after treatment with the nonaromatizable androgen dihydrotestosterone (DHT; 500 mug/d, s.c., 2 d). Administration of 1 mg of letrozole, a powerful nonsteroidal aromatase inhibitor, 1 hr before the steroid injections almost completely blocked the synaptic response to testosterone, resulting in a mean synapse density (0.723 +/- 0.003 spine synapse/mum(3)) only slightly higher than in OVX control rats. By contrast, the response to DHT was unaffected by letrozole pretreatment. These data suggest that androgen secretion during the female reproductive cycle may contribute to cyclical changes in hippocampal synaptic density. They also indicate that androgen treatment may be as effective as estrogen replacement in reversing the decline in hippocampal CA1 spine synapses that follows loss of ovarian function. Induction of hippocampal synapse formation by androgen is not mediated entirely via intracerebral estrogen biosynthesis, however, because aromatase-independent mechanisms also significantly affect CA1 spine synapse density.