Effects of Cholinergic Lesions and Cholinesterase Inhibitors on Aromatase and Estrogen Receptor Expression in Different Regions of the Rat Brain.
Effects of Cholinergic Lesions and Cholinesterase Inhibitors on Aromatase and Estrogen Receptor Expression in Different Regions of the Rat Brain.
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DOI：
10.1016/j.neuroscience.2018.05.033
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发表时间：
2018-08-01
期刊：
影响因子：
3.3
通讯作者：
Gibbs RB
中科院分区：
文献类型：
--
作者：
Li J;Rao D;Gibbs RB
胆碱能投射已被证明以影响突触可塑性和认知表现的方式与雌激素相互作用。其机制尚不清楚。本研究的目的是探讨胆碱能投射是否通过影响芳香化酶（ARO）来影响脑雌激素的产生，或者通过影响雌激素受体的表达来影响雌激素信号。在第一个实验中，卵巢切除大鼠接受隔内注射的选择性免疫毒素192 IgG-皂草素破坏胆碱能输入海马。在第二个实验中，切除卵巢的大鼠每天接受胆碱酯酶抑制剂多奈哌齐或加兰他敏的腹膜内注射，持续1周。在海马、额叶皮质、杏仁核和视前区定量ARO活性和ARO、ERα、ER β和GPR 30 mRNA的相对水平。结果表明，胆碱能损伤有效地消除了胆碱能输入海马，但对ARO或ER mRNA的相对水平没有显着影响。同样，注射胆碱酯酶抑制剂对大脑大部分区域的ARO或ER表达没有影响。这表明胆碱能输入对突触可塑性和神经元功能的影响不是通过对局部雌激素产生或ER表达的影响来介导的。一个例外是杏仁核，其中用加兰他敏治疗与ARO活性的显著增加相关。杏仁核是记录恐惧和焦虑的关键结构。因此，这一发现可能与接受记忆障碍治疗的老年患者以及与恐惧和焦虑症作斗争的老年患者有关。
Cholinergic projections have been shown to interact with estrogens in ways that influence synaptic plasticity and cognitive performance. The mechanisms are not well understood. The goal of this study was to investigate whether cholinergic projections influence brain estrogen production by affecting aromatase (ARO), or influence estrogen signaling by affecting estrogen receptor expression. In the first experiment, ovariectomized rats received intraseptal injection of the selective immunotoxin 192IgG-saporin to destroy cholinergic inputs to the hippocampus. In the second experiment ovariectomized rats received daily intraperitoneal injections of the cholinesterase inhibitors donepezil or galantamine for 1 week. ARO activity and relative levels of ARO, ERα, ERß, and GPR30 mRNAs were quantified in the hippocampus, frontal cortex, amygdala and preoptic area. Results show that the cholinergic lesions effectively removed cholinergic inputs to the hippocampus, but had no significant effect on ARO or on relative levels of ER mRNAs. Likewise, injections of the cholinesterase inhibitors had no effect on ARO or ER expression in most regions of the brain. This suggests that effects of cholinergic inputs on synaptic plasticity and neuronal function are not mediated by effects on local estrogen production or ER expression. One exception was the amygdala where treating with galantamine was associated with a significant increase in ARO activity. The amygdala is a key structure involved in registering fear and anxiety. Hence this finding may be clinically relevant to elderly patients who are treated for memory impairment and who also struggle with fear and anxiety disorders.
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DOI：
10.1177/1073858413519865
发表时间：
2014-10
期刊：
The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
影响因子：
--
作者：
Bean LA;Ianov L;Foster TC
通讯作者：
Foster TC
影响因子：
3.8
作者：
Fitz, Nicholas F.;Gibbs, Robert B.;Johnson, David A.
通讯作者：
Johnson, David A.
影响因子：
3.2
作者：
Balthazart, J;Baillien, M;Ball, GF
通讯作者：
Ball, GF
影响因子：
3.5
作者：
Daniel, JM;Fader, AJ;Dohanich, GP
通讯作者：
Dohanich, GP
影响因子：
3.8
作者：
Fitz, Nicholas F.;Gibbs, Robert B.;Johnson, David A.
通讯作者：
Johnson, David A.