雌二醇经雌激素受体调控分拣蛋白相关受体A对小鼠海马神经元树突棘密度和突触蛋白表达的影响

张沂洲; 李莎; 米世雄; 左洪春; 张倩倩; 李晗琳; 雷梓晗; 张东泽; 崔慧先

doi:10.16098/j.issn.0529-1356.2023.03.002

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解剖学报 ›› 2023, Vol. 54 ›› Issue (3) : 261-268. DOI: 10.16098/j.issn.0529-1356.2023.03.002

神经生物学

雌二醇经雌激素受体调控分拣蛋白相关受体A对小鼠海马神经元树突棘密度和突触蛋白表达的影响

张沂洲^1,2,3 李莎^1,2,3米世雄^1,2,3左洪春^1,2张倩倩⁴ 李晗琳⁵ 雷梓晗⁵ 张东泽⁵ 崔慧先^1,2,3*

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Effect of estradiol regulating sortilin-related receptor A expression on hippocampal spine density and synaptic protein expression via estrogen receptor of mouse

ZHANG Yi-zhou^1,2,3 LI Sha^1,2,3 MI Shi-xiong^1,2,3 ZUO Hong-chun^1,2 ZHANG Qian-qian⁴ LI Han-lin⁵ LEI Zi-han⁵ ZHANG Dong-ze⁵ CUI Hui-xian^1,2,3*

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摘要

目的探讨雌二醇（E2）调控分拣蛋白相关受体A（SorLA）表达对小鼠海马神经元树突棘密度和突触蛋白表达的影响及机制。方法 32只C57BL/6雌性小鼠随机分为假手术（sham）组、卵巢切除（OVX）组、卵巢切除+E2组（OVX+E2）组、卵巢切除+氟维司琼（Fu）+E2组（OVX+Fu+E2）组，通过Western blotting和免疫组织化学染色检测小鼠海马CA1区SorLA表达；40只C57BL/6雌性小鼠随机分为假手术+空白病毒（sham+NC-sgRNA）组、卵巢切除+空白病毒（OVX+NC-sgRNA）组、卵巢切除+空白病毒+E2（OVX+NC-sgRNA+E2）组、卵巢切除+SorLA敲降病毒+E2 组（OVX+Sorl1-sgRNA+E2）组，通过高尔基染色检测小鼠海马CA1区神经元树突棘密度；通过Western blotting 和免疫组织化学染色检测小鼠海马CA1区突触后致密蛋白95（PSD-95）和突触蛋白1（SYN1）表达。结果与sham组相比，和OVX组和OVX+Fu+E2组SorLA蛋白表达显著降低（P<0.05），和OVX+E2组差异无显著性（P >0.05）；与sham+NC-sgRNA组相比，OVX+NC-sgRNA组和OVX+Sorl1-sgRNA+E2组树突棘密度和PSD-95、SYN1表达显著降低（P <0.05），与OVX+NC-sgRNA+E2组差异无显著性（P>0.05）。结论 E2可通过雌激素受体上调SorLA表达，进而增加小鼠海马神经元树突棘密度和突触蛋白表达。

Abstract

Objective To study the effect and mechanism of estradiol (E2) regulating sortilin-related receptor A (SorLA) expression on hippocampal spine density and synaptic protein expression of mouse. Methods Thirty-two C57BL/6 female mice were randomly divided into sham group, ovariectomized(OVX) group, OVX+E2 group, and OVX+fulvestrant(Fu)+E2 group; The SorLA expression in hippocampal CA1 region of mouse was detected by Western blotting and immunohistochemical staining. Forty C57BL/6 female mice were randomly divided into sham+NC-sgRNA group, OVX+NC-sgRNA group, OVX+NC-sgRNA+E2 group, and OVX+sortilin-related receptor 1(Sorl1)-sgRNA+E2; the spine density in hippocampal CA1 region was detected by Golgi-Cox staining and the postsynaptic density protein 95 (PSD-95) and synapsin-1 (SYN1) expression in hippocampal CA1 region were detected by Western blotting and immunohistochemical staining. Results Compared with the sham group, the SorLA expression in OVX group and OVX+Fu+E2 group decreased significantly (P<0.05), but OVX+E2group had no significant difference (P>0.05). Compared with the sham+NC-sgRNA group, the density of dendritic spines, and the PSD-95, SYN1 expression of OVX+NC-sgRNA group and OVX+Sorl1-sgRNA+E2 group decreased significantly (P<0.05), but OVX+NC-sgRNA+E2 group had no significant difference (P>0-05). Conclusion E2 may upregulate SorLA expression through estrogen receptor and then promote the hippocampal spine density and synaptic protein expression of mouse.

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Key words

Estradiol / Estrogen receptor / Sortilin-related receptor A / Western blotting / Immunohistochemistry / Golgi-Cox staining / Mouse

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张沂洲李莎米世雄左洪春张倩倩李晗琳雷梓晗张东泽崔慧先. 雌二醇经雌激素受体调控分拣蛋白相关受体A对小鼠海马神经元树突棘密度和突触蛋白表达的影响[J]. 解剖学报. 2023, 54(3): 261-268 https://doi.org/10.16098/j.issn.0529-1356.2023.03.002

ZHANG Yi-zhou LI Sha MI Shi-xiong ZUO Hong-chun ZHANG Qian-qian LI Han-lin LEI Zi-han ZHANG Dong-ze CUI Hui-xian.

Effect of estradiol regulating sortilin-related receptor A expression on hippocampal spine density and synaptic protein expression via estrogen receptor of mouse

[J]. Acta Anatomica Sinica. 2023, 54(3): 261-268 https://doi.org/10.16098/j.issn.0529-1356.2023.03.002

中图分类号： R322.81

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