Gonadal Steroids Maintain 24 h Acetylcholine Release in the Hippocampus: Organizational and Activational Effects in Behaving Rats
Gonadal Steroids Maintain 24 h Acetylcholine Release in the Hippocampus: Organizational and Activational Effects in Behaving Rats
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DOI：
10.1523/jneurosci.5301-08.2009
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发表时间：
2009-03-25
影响因子：
5.3
通讯作者：
Kimura, Fukuko
中科院分区：
文献类型：
--
作者：
Mitsushima, Dai;Takase, Kenkichi;Kimura, Fukuko
在学习或探索过程中，背侧海马区的细胞外乙酰胆碱(ACh)水平升高，表现出性别特异性的24小时释放谱。为了探讨性腺类固醇激素对性特异性ACh水平的激活作用及其与自发运动活动的相关性，我们对这些参数进行了24小时的同步观察。性腺切除严重降低了ACh水平，而性腺切除男性用睾酮替代或性腺切除女性用17β-雌二醇替代成功地恢复了ACh水平。17β-雌二醇刺激不能恢复性腺切除男性的ACh水平，而性腺切除女性的睾酮替代未能使ACh水平提高到睾酮诱导的性腺切除男性的水平，显示出性别特异性的激活效应。性腺切除或性腺类固醇替代对雄性小鼠自发活动无明显影响，但17β-雌二醇可增强去性腺雌性小鼠的自发运动活动。性腺切除严重降低了ACh释放与活动水平之间的相关性，但性腺切除男性的睾酮替代或性腺切除女性的17β-雌二醇替代成功地恢复了ACh释放与活动水平的相关性。为了进一步分析性腺类固醇的性别特异性效应，我们研究了性腺类固醇对雌性大鼠ACh释放的组织效应。新生儿睾酮或17β-雌二醇治疗不仅增加了ACh水平，还改变了它们，使其类似于男性特有的ACh释放特性，而不影响自发运动活动的水平。结论：性腺类固醇维持ACh水平的激活作用及其与自发活动的高度相关性具有性别特异性，性腺类固醇的组织效应提示雌激素受体介导隔-海马胆碱能系统的男性化。
Extracellular acetylcholine (ACh) levels in the dorsal hippocampus increases during learning or exploration, exhibiting a sex-specific 24 h release profile. To examine the activational effect of gonadal steroid hormones on the sex-specific ACh levels and its correlation with spontaneous locomotor activity, we observed these parameters simultaneously for 24 h. Gonadectomy severely attenuated the ACh levels, whereas the testosterone replacement in gonadectomized males or 17 beta-estradiol replacement in gonadectomized females successfully restored the levels. 17 beta-Estradiol-priming in gonadectomized males could not restore the ACh levels, and testosterone replacement in gonadectomized females failed to raise ACh levels to those seen in testosterone-primed gonadectomized males, revealing a sex-specific activational effect. Spontaneous locomotor activity was not changed in males by gonadectomy or the replacement of gonadal steroids, but 17 beta-estradiol enhanced the activity in gonadectomized females. Gonadectomy severely reduced the correlation between ACh release and activity levels, but the testosterone replacement in gonadectomized males or 17 beta-estradiol replacement in gonadectomized females successfully restored it. To further analyze the sex-specific effect of gonadal steroids, we examined the organizational effect of gonadal steroids on the ACh release in female rats. Neonatal testosterone or 17 beta-estradiol treatment not only increased the ACh levels but also altered them to resemble male-specific ACh release properties without affecting levels of spontaneous locomotor activity. We conclude that the activational effects of gonadal steroids maintaining the ACh levels and the high correlation with spontaneous locomotor activity are sex-specific, and that the organizational effects of gonadal steroids suggest estrogen receptor-mediated masculinization of the septo-hippocampal cholinergic system.