Role of the medial septum diagonal band of Broca cholinergic neurons in oestrogen-induced spine synapse formation on hippocampal CA1 pyramidal cells of female rats

Role of the medial septum diagonal band of Broca cholinergic neurons in oestrogen-induced spine synapse formation on hippocampal CA1 pyramidal cells of female rats
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DOI:
10.1046/j.1460-9568.2003.02637.x
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发表时间:
2003-05-01
影响因子:
3.4
通讯作者:
Leranth, C
Leranth, C
中科院分区:
医学3区
文献类型:
--
作者:
Lâm, TT;Leranth, C

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已知雌激素会影响海马 CA1 亚区锥体细胞棘突触的可塑性。除了雌激素对海马的直接作用外,已知皮质下结构介导的雌激素作用也很重要。本研究的目的是探讨布罗卡内侧隔对角带(MSDB)是否参与介导雌激素对海马的作用。特别关注投射到海马的胆碱能 MSDB 神经元的作用,因为其中相当大的群体含有雌激素受体,因此可能对雌激素信号敏感。成年雌性大鼠被切除卵巢。将充满雌二醇和胆固醇的插管(对照)植入 MSDB 中。为了选择性地消除雌激素治疗动物的 MSDB 神经元的胆碱能群体,在插管植入前 1 周,向一组大鼠的侧脑室注射 192 IgG-皂草素 (SAP)。使用抗胆碱乙酰转移酶和小清蛋白 (PA) 进行的免疫染色表明,在 SAP 大鼠的 MSDB 中,胆碱能而非含 PA 的 GABA 能神经元显着减少。对所有动物组之间 CA1 区锥体细胞的棘突触密度进行比较电子显微镜无偏立体学分析。接受雌二醇填充插管的大鼠表现出比对照动物更高的脊柱突触密度(30%)。接受 SAP 治疗的雌激素治疗大鼠与对照组没有显着差异。因此,这一观察表明隔海马胆碱能神经元参与介导雌激素对海马的作用。讨论了这一观察结果与记忆功能和阿尔茨海默病的相关性。
Oestrogen is known to influence pyramidal cell spine synapse plasticity in the CA1 subfield of the hippocampus. Apart from direct oestrogen action on the-hippocampus, oestrogen effects mediated by subcortical structures are known to be important. The purpose of this study was to investigate whether the medial septum diagonal band of Broca (MSDB) takes part in mediating oestrogen effects to the hippocampus. Special attention was given to the role of cholinergic MSDB neurons that project to the hippocampus, as a rather large population of them contains oestrogen receptors and, consequently, may be sensitive to oestrogen signals. Adult female rats were ovariectomized. Oestradiol- and cholesterol-filled cannulae (control) were implanted into the MSDB. To selectively eliminate the cholinergic population of MSDB neurons of oestrogen-treated animals, a group of rats was injected with 192 IgG-saporin (SAP) into the lateral ventricle 1 week before the cannula implant. Immunostaining with anti-choline acetyltransferase and parvalbumin (PA) showed that cholinergic but not PA-containing GABAergic neurons were substantially reduced in the MSDB of SAP rats. Comparative electron microscopic unbiased stereological analysis on the spine synapse density of CA1 area pyramidal cells was performed between all animal groups. Rats that received oestradiol-filled cannulae showed a higher (30%) spine synapse density than control animals. Oestrogen-treated rats that had received SAP treatment showed no significant difference to controls. Thus, this observation indicates that septo-hippocampal cholinergic neurons are involved in mediating oestrogen effects to the hippocampus. The relevance of this observation to mnemonic functions and Alzheimer's disease is discussed.