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绝经后大鼠大脑中雌激素受体与微管动力学之间的关系。

The relationship between estrogen receptors and microtubule dynamics in post-menopausal rat brain.

作者信息

Selina Aksak Karamese, Murat Karamese, Emre Karakus, Ismail Malkoc, Bunyami Unal, Cemal Gundogdu

机构信息

Kafkas University, Medical Faculty, Department of Histology and Embryology, 36100 Kars, Turkey.

Kafkas University, Medical Faculty, Department of Microbiology, 36100 Kars, Turkey.

出版信息

Acta Histochem. 2015 Oct;117(8):747-51. doi: 10.1016/j.acthis.2015.08.005. Epub 2015 Aug 28.

Abstract

INTRODUCTION

Estrogen is one of the most important regulators of neuron function. There is a broad consensus that a loss of estrogen is associated with neurodegeneration in the hippocampus which leads to cognitive impairment. Hematopoietic-Pbx-interaction-protein (HPIP) is a novel scaffolding protein which interacts with microtubules and estrogen receptors. In this study, we investigated the presence and role of HPIP in hippocampal neurons and examined the relationship between estrogen receptors and microtubule damage in post-menopausal rat brains.

METHOD

Eighty female Wistar albino rats, 12 weeks old, were divided into 10 groups: control, control+17-β-estradiol, control+tamoxifen, control+mitogen-activated protein kinases (MAPK) inhibitor, control+phosphoinositide 3-kinase (PI3-K) inhibitor, ovariectomized, ovariectomized+17-β-estradiol, ovariectomized+tamoxifen, ovariectomized+MAPK inhibitor, and ovariectomized+PI3-K inhibitor. Light and electron microscopic examinations were performed. Real-time polymerase chain reaction (PCR) was used to determine the expression level of HPIP in experimental groups.

RESULTS

Light and electron microscopic examinations revealed morphological changes in hippocampal neuron axons. Axonal fluctuations and shrinkage were detected in all ovariectomized groups. HPIP was detected in all neurons with difference expression levels.

CONCLUSION

Proof that the HPIP protein can be found on hippocampal neurons may give rise to a new focus on neurodegeneration in post-menopausal women. Future molecular and pharmacological studies should be performed to reduce the rate of cognitive symptoms resulting from hippocampal neurodegeneration.

摘要

引言

雌激素是神经元功能最重要的调节因子之一。人们普遍认为,雌激素缺乏与海马体神经退行性变相关,进而导致认知障碍。造血 PBX 相互作用蛋白(HPIP)是一种新型支架蛋白,可与微管和雌激素受体相互作用。在本研究中,我们调查了 HPIP 在海马神经元中的存在及作用,并研究了绝经后大鼠大脑中雌激素受体与微管损伤之间的关系。

方法

将 80 只 12 周龄的雌性 Wistar 白化大鼠分为 10 组:对照组、对照组 + 17-β-雌二醇、对照组 + 他莫昔芬、对照组 + 丝裂原活化蛋白激酶(MAPK)抑制剂、对照组 + 磷脂酰肌醇 3-激酶(PI3-K)抑制剂、去卵巢组、去卵巢 + 17-β-雌二醇组、去卵巢 + 他莫昔芬组、去卵巢 + MAPK 抑制剂组、去卵巢 + PI3-K 抑制剂组。进行光镜和电镜检查。采用实时聚合酶链反应(PCR)测定各实验组中 HPIP 的表达水平。

结果

光镜和电镜检查显示海马神经元轴突存在形态学变化。在所有去卵巢组中均检测到轴突波动和萎缩。在所有神经元中均检测到 HPIP,但表达水平存在差异。

结论

HPIP 蛋白可在海马神经元中被发现,这一证据可能会引发对绝经后女性神经退行性变的新关注。未来应开展分子和药理学研究,以降低海马体神经退行性变导致的认知症状发生率。

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