Research Center for Cognitive and Behavioral Sciences, Tehran University of Medical Sciences, Tehran, Iran; School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
Department of Neurosciences and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Neuropeptides. 2024 Dec;108:102474. doi: 10.1016/j.npep.2024.102474. Epub 2024 Sep 18.
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.
促性腺激素释放激素 (GnRH) 和褪黑素能系统之间存在相互作用。褪黑素合成的关键酶（芳烷基胺 N-乙酰转移酶，AANAT）和 GnRH 受体都在海马体中表达。虽然已经表明海马体中的 AANAT 酶活性对于正常的海马体认知功能是必要的，但它们在长时程增强 (LTP) 诱导中的作用尚未完全理解。在目前的研究中，研究了 GnRH 对 LTP 诱导的影响，同时抑制了海马体褪黑素的合成。通过 AANAT-siRNA 给药抑制褪黑素的合成，并用体内场电位电生理记录诱导 LTP。动物被分为 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套管以接受载体试剂、AANAT siRNA（0.5μg/海马）、GnRH（1ng/大鼠）和 AANAT siRNA+GnRH。通过新物体识别测试评估识别记忆。通过刺激 Schaffer 侧支通路进行场电位电生理学实验，并通过高频刺激 (HFS) 进行 LTP 诱导。记录后，将动物的大脑分离并迅速冷冻，通过 LC-MS 测量海马褪黑素水平和 qRT-PCR 测量 AANAT mRNA 水平。GnRH 注射到海马体中增加了局部 AANAT-mRNA 表达和褪黑素水平。与完整组、载体组和 siRNA 组相比，GnRH 处理的动物的 LTP 幅度更高。而 AANAT-siRNA 降低海马褪黑素水平抑制 LTP 和损害识别记忆，但 GnRH 阻止了这些不利影响。数据表明，GnRH 对 AANAT-siRNA 诱导的 LTP 下降具有保护作用。保护机制至少部分可能与局部 AANAT-mRNA 表达增加有关。
