GnRH对AANAT-siRNA诱导的长期延时损伤的保护作用

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-09-18 DOI:10.1016/j.npep.2024.102474

Leila Karimi-Zandi , Tahereh Ghorbandaiepour , Maryam Zahmatkesh , Esmaeil Sadroddiny

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引用次数: 0

摘要

促性腺激素释放激素（GnRH）和褪黑激素能系统之间存在相互作用。褪黑激素合成的关键酶（芳基烷基胺 N-乙酰转移酶，AANAT）和促性腺激素释放激素受体都在海马中表达。有研究表明，海马 AANAT 酶的活性是海马正常认知功能所必需的，但它们在长期延时（LTP）诱导中的作用尚未完全明了。本研究在抑制海马褪黑激素合成的同时，研究了GnRH对LTP诱导的影响。通过AANAT-siRNA抑制褪黑激素的合成，并使用体内场电位电生理记录诱导LTP。动物被分为 5 组：动物分为 5 组：完整组、载体组、siRNA 组、GnRH 组和 siRNA+GnRH 组。除完整组外，所有动物均接受立体定向手术和海马内插管，分别接受载体、AANAT siRNA（0.5 μg/hip）、GnRH（1 ng/rat）和AANAT siRNA+GnRH。识别记忆通过新物体识别测试进行评估。场电位电生理学实验通过刺激沙弗侧路进行，LTP诱导通过高频刺激（HFS）进行。记录结束后，动物大脑被分离并快速冷冻，以进一步通过LC-MS测定海马褪黑激素水平，并通过qRT-PCR测定AANAT mRNA水平。在海马中注射 GnRH 增加了局部 AANAT mRNA 的表达和褪黑激素水平。经GnRH处理的动物的LTP振幅高于完整组、车辆组和siRNA组。AANAT-siRNA 降低了海马褪黑激素水平，抑制了 LTP 并损害了识别记忆，而 GnRH 则防止了这些不利影响。这些数据表明，GnRH对AANAT-siRNA诱导的LTP下降具有保护作用。这种保护机制至少部分可能与局部 AANAT-mRNA 表达的增加有关。

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GnRH protective effects against long-term potentiation impairment induced by AANAT-siRNA

There is an interplay between the gonadotropin-releasing hormone (GnRH) and melatoninergic systems. The key enzyme of melatonin synthesis (arylalkylamine N-acetyltransferase, AANAT), and GnRH receptors are expressed in the hippocampus. While it has been shown that hippocampal AANAT enzyme activity is necessary for proper hippocampal cognitive function, their role in long-term potentiation (LTP) induction is not fully understood. In current study, the impact of GnRH on LTP induction was investigated, while hippocampal melatonin synthesis had been inhibited. The melatonin synthesis was inhibited by AANAT-siRNA administration, and LTP was induced using in vivo field potential electrophysiological recording.

Animals were divided into 5 groups: Intact, vehicle, siRNA, GnRH and siRNA+GnRH. All animals, except intact group, experienced the stereotaxic surgery and intra-hippocampal cannulation to receive vehicle agent, AANAT siRNA (0.5 μg/hip), GnRH (1 ng/rat), and AANAT siRNA+GnRH. The recognition memory was assessed by Novel object recognition test. The field potential electrophysiology experiment was conducted by stimulating the Schaffer collateral pathway, and LTP induction was carried out through high-frequency stimulation (HFS). After recording, animals' brain was isolated and quickly frozen for further hippocampal melatonin levels measurement by LC-MS and AANAT mRNA levels by qRT-PCR.

GnRH injection in the hippocampus increased local AANAT-mRNA expression and melatonin levels. GnRH-treated animals displayed higher LTP amplitude compared to intact, vehicle and siRNA groups. While the reduction in hippocampal melatonin levels by AANAT-siRNA inhibited LTP and impaired recognition memory, the GnRH prevented these adverse effects. The data suggests that GnRH have protective effects against AANAT-siRNA-induced LTP decline. The protective mechanism at least partially, may be related to the increased expression of local AANAT-mRNA.

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464