海马毒蕈碱M4受体mRNA表达可能影响中枢胆碱能活性，引起外周肾上腺素增强恐惧记忆。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2025-02-21 DOI:10.1016/j.neuropharm.2025.110382

Ana Oliveira , Márcia Azevedo , Rafaela Seixas , Soraia Silva , Raquel Martinho , Paula Serrão , Elisabete Silva , Mónica Moreira-Rodrigues

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引用次数: 0

摘要

肾上腺素（Ad）通过提高血糖来增强情境恐惧记忆，可能增强海马乙酰胆碱合成。然而，目前尚不清楚外周Ad是否会影响胆碱能系统，从而促进情境恐惧记忆的增强。我们的目的是评估外周Ad是否会改变毒蕈碱受体的表达，以及胆碱能系统是否参与外周Ad情境恐惧记忆的强化作用。野生型（WT）和Ad缺陷雄性小鼠（129x1/SvJ）先进行恐惧调节，然后进行腹腔预训练和环境前给药，分别给予Ad （0.1 mg/kg）、阿托品（10 mg/kg）、甲基拉托品（0.5 mg/kg）、Ad （0.1 mg/kg）加阿托品（10 mg/kg）或对照物（NaCl, 0.9%）。获得了冲击响应性和冻结行为。观察海马M1、M2和M4 mRNA的表达。与WT小鼠相比，ad缺陷小鼠海马毒蕈碱M4亚型受体mRNA表达降低。在给药ad缺陷小鼠中，与载药ad缺陷小鼠相比，海马毒蕈碱M4亚型受体mRNA表达增加。在环境日，与对照或甲基拉托品给药的WT小鼠相比，阿托品给药的WT小鼠表现出更低的冷冻行为。此外，与给予Ad的Ad缺陷小鼠相比，给予Ad加阿托品的Ad缺陷小鼠的冷冻行为减少。综上所述，Ad缺陷小鼠情境恐惧记忆障碍与海马毒蕈碱M4亚型受体下调表达有关，Ad可逆转这种下调表达。这可能与周边Ad诱发的情境恐惧记忆巩固或提取有关。此外，Ad情境恐惧记忆的影响可能是由于海马毒蕈碱亚型M4表达增加，这可能导致中枢神经系统胆碱能活性增加。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Hippocampus muscarinic M4 receptor mRNA expression may influence central cholinergic activity, causing fear memory strengthening by peripheral adrenaline

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Hippocampus muscarinic M4 receptor mRNA expression may influence central cholinergic activity, causing fear memory strengthening by peripheral adrenaline

Adrenaline (Ad) strengthens contextual fear memory by increasing blood glucose, possibly enhancing hippocampus acetylcholine synthesis. Nevertheless, it is unclear if peripheral Ad influences the cholinergic system, contributing to contextual fear memory strengthening. We aimed to evaluate whether peripheral Ad alters muscarinic receptor expression and if the cholinergic system is involved in peripheral Ad contextual fear memory strengthening effect.

Wild-type (WT) and Ad-deficient male mice (129 × 1/SvJ) underwent a fear conditioning procedure followed by intraperitoneal pre-training and pre-context administration of Ad (0.1 mg/kg), atropine (10 mg/kg), methylatropine (0.5 mg/kg), Ad (0.1 mg/kg) plus atropine (10 mg/kg) or vehicle (NaCl, 0.9%). Shock responsiveness and freezing behaviour were accessed. Hippocampal M₁, M₂, and M₄ mRNA expression were evaluated.

Ad-deficient mice presented decreased hippocampal muscarinic M₄ subtype receptor mRNA expression compared to WT mice. In Ad-administered Ad-deficient mice, hippocampal muscarinic M₄ subtype receptor mRNA expression increased compared with vehicle-administered Ad-deficient mice. On the context day, atropine-administered WT mice presented decreased freezing behaviour compared to vehicle or methylatropine-administered WT mice. Moreover, Ad plus atropine-administered Ad-deficient mice led to decreased freezing behaviour compared to Ad-administered Ad-deficient mice.

In conclusion, Ad-deficient mice's contextual fear memory impairment was associated with hippocampal muscarinic M₄ subtype receptor down expression, which was reversed by Ad. This may be related to contextual fear memory consolidation or retrieval induced by peripheral Ad. Furthermore, the effect of Ad contextual fear memory might be due to increased hippocampus muscarinic subtype M₄ expression, which may contribute to increased cholinergic activity in the central nervous system.

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来源期刊

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).