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褪黑素降低老年雄性大鼠海马体和前额叶皮质的过度兴奋性并增强睡眠振荡。

Melatonin Reduced Hyperexcitability and Enhanced Sleep Oscillations in the Hippocampus and Prefrontal Cortex of Aged Male Rats.

作者信息

Karimani Farnaz, Eivani Mehdi, Asgari Taei Afsaneh, Abolghasemi Dehaqani Mohammad-Reza, Dargahi Leila

机构信息

Neuroscience Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Brain and Cognitive Science Lab, Center for Convergent Technologies, University of Tehran, Tehran, Iran.

出版信息

Neurochem Res. 2025 Jul 22;50(4):243. doi: 10.1007/s11064-025-04497-6.

DOI:10.1007/s11064-025-04497-6
PMID:40694166
Abstract

Aging is commonly associated with cognitive decline, particularly in memory, and is linked to neuronal hyperexcitability and disrupted sleep-related oscillations in key brain regions such as the hippocampus and prefrontal cortex. Melatonin has been proposed as a potential therapeutic agent to counteract age-related cognitive impairments. In this study, 24-month-old male Wistar rats were treated with melatonin (10 mg/kg, intraperitoneally) for 30 days. Local field potentials were recorded from the hippocampus and prefrontal cortex to assess neuronal activity. Memory performance was evaluated using the novel object recognition test, and qPCR measured expression levels of inflammatory and amyloidogenesis markers. Melatonin treatment significantly reduced neuronal hyperexcitability, enhanced delta and theta oscillations, and increased sleep spindle amplitude, which were associated with improved memory performance. Additionally, melatonin attenuated the expression of pro-inflammatory markers without affecting the expression of amyloidogenesis-related genes. These findings suggest that melatonin may enhance cognitive function in aging by modulating neuronal excitability, sleep oscillations, and neuroinflammatory processes.

摘要

衰老通常与认知能力下降有关,尤其是在记忆方面,并且与神经元过度兴奋以及海马体和前额叶皮质等关键脑区中与睡眠相关的振荡紊乱有关。褪黑素已被提议作为一种潜在的治疗药物来对抗与年龄相关的认知障碍。在本研究中,对24月龄雄性Wistar大鼠腹腔注射褪黑素(10毫克/千克),持续30天。记录海马体和前额叶皮质的局部场电位以评估神经元活动。使用新物体识别测试评估记忆表现,并通过qPCR测量炎症和淀粉样蛋白生成标志物的表达水平。褪黑素治疗显著降低了神经元的过度兴奋性,增强了δ波和θ波振荡,并增加了睡眠纺锤波振幅,这些都与记忆表现的改善有关。此外,褪黑素减弱了促炎标志物的表达,而不影响淀粉样蛋白生成相关基因的表达。这些发现表明,褪黑素可能通过调节神经元兴奋性、睡眠振荡和神经炎症过程来增强衰老过程中的认知功能。

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本文引用的文献

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Melatonin alleviates cognition impairment by antagonizing brain insulin resistance in aged rats fed a high-fat diet.褪黑素通过拮抗高脂肪饮食喂养的老年大鼠脑胰岛素抵抗来减轻认知障碍。
J Pineal Res. 2019 Sep;67(2):e12584. doi: 10.1111/jpi.12584. Epub 2019 Jun 3.
2
Long-term administration of melatonin attenuates neuroinflammation in the aged mouse brain.长期给予褪黑素可减轻老年小鼠大脑中的神经炎症。
EXCLI J. 2018 Jul 2;17:634-646. doi: 10.17179/excli2017-654. eCollection 2018.
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Melatonin induces mechanisms of brain resilience against neurodegeneration.
褪黑素诱导大脑抵抗神经退行性变的弹性机制。
J Pineal Res. 2018 Nov;65(4):e12515. doi: 10.1111/jpi.12515. Epub 2018 Jul 4.
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Transcranial slow oscillation stimulation during NREM sleep enhances acquisition of the radial maze task and modulates cortical network activity in rats.非快速眼动睡眠期间经颅慢振荡刺激可增强大鼠放射状迷宫任务的习得并调节皮质网络活动。
Front Behav Neurosci. 2014 Jan 8;7:220. doi: 10.3389/fnbeh.2013.00220. eCollection 2013.
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NREM Sleep Oscillations and Brain Plasticity in Aging.非快速眼动睡眠振荡与衰老中的大脑可塑性。
Front Neurol. 2012 Dec 14;3:176. doi: 10.3389/fneur.2012.00176. eCollection 2012.
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Melatonin modulates the GABAergic response in cultured rat hippocampal neurons.褪黑素调节培养的大鼠海马神经元中的 GABA 能反应。
J Pharmacol Sci. 2012;119(2):177-85. doi: 10.1254/jphs.11183fp. Epub 2012 May 31.
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Melatonin improves D-galactose-induced aging effects on behavior, neurogenesis, and lipid peroxidation in the mouse dentate gyrus via increasing pCREB expression.褪黑素通过增加 pCREB 表达改善 D-半乳糖诱导的小鼠齿状回行为、神经发生和脂质过氧化的衰老效应。
J Pineal Res. 2012 Jan;52(1):21-8. doi: 10.1111/j.1600-079X.2011.00912.x. Epub 2011 Jul 1.
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Melatonin in experimental seizures and epilepsy.褪黑素在实验性癫痫发作和癫痫中的作用。
Pharmacol Rep. 2011;63(1):1-11. doi: 10.1016/s1734-1140(11)70393-0.
9
Involvement of GABAergic and cholinergic medial septal neurons in hippocampal theta rhythm.γ-氨基丁酸能和胆碱能内侧隔区神经元参与海马θ节律。
Hippocampus. 2005;15(3):381-92. doi: 10.1002/hipo.20062.
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Fluctuation of blood melatonin concentrations with age: result of changes in pineal melatonin secretion, body growth, and aging.血液褪黑素浓度随年龄的波动:松果体褪黑素分泌、身体生长和衰老变化的结果。
J Pineal Res. 1990;8(2):179-92. doi: 10.1111/j.1600-079x.1990.tb00678.x.