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羽田雄性大鼠海马中与焦虑相关的候选基因:神经介素U在海马中的抗焦虑作用。

Candidate Anxiety-Related Genes in the Hippocampus of Hatano Male Rats: Anxiolytic Action of Neuromedin U in the Hippocampus.

作者信息

Sato Kaito, Ishii Atsuhiro, Kobayashi Shohei, Hatakeyama Taichi, Watanabe Gen, Soga Tomoko, Parhar Ishwar, Matsuwaki Takashi, Moriya Shogo, Ohta Ryo, Chiba Shuichi, Kawaguchi Maiko

机构信息

Lab of Animal Behavior and Environmental Science, Graduate School of Agriculture, Meiji University, Kawasaki, Kanagawa, Japan.

Organization for the Strategic Coordination of Research and Intellectual Property, Meiji University, Kawasaki, Kanagawa, Japan.

出版信息

Neuropsychopharmacol Rep. 2025 Jun;45(2):e70018. doi: 10.1002/npr2.70018.


DOI:10.1002/npr2.70018
PMID:40275722
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12022414/
Abstract

Identifying genes involved in anxiety is important to elucidate the mechanisms of anxiety disorders. Hatano high avoidance animals (HAA) and low avoidance animals (LAA) are inbred strains that are selected based on their performance in an active avoidance test. HAA shows a higher level of anxiety-like behavior than LAA. The present study focuses on the hippocampus, which is associated with anxiety-like behavior, and used microarray analysis and RT-qPCR to select genes with differential expression in the hippocampus between HAA and LAA (Experiment 1). The microarray analysis revealed differences in 498 gene expressions between HAA and LAA, of which 21 genes were ligand-receptor related in the nervous system. We selected nine genes based on p value and conducted RT-qPCR, which identified seven genes whose expressions were higher in LAA than in HAA. We focused on the gene, neuromedin U receptor 2 (Nmur2), which showed significantly different expression levels between HAA and LAA. Further, we conducted a behavioral test to evaluate anxiety levels by administering neuromedin U (NmU), an agonist for NmUR2, into the hippocampus (Experiment 2). NmU treatment did not affect the results of the open field test or the elevated plus maze test, which are unconditioned response models of anxiety. However, in the passive avoidance test, a conditioned response model of anxiety, the NmU group showed less anxiety-like behavior than the control group. This is the first study to show that NmU suppresses the conditioned response model of anxiety via the hippocampus, indicating that NmUR2 in the hippocampus may be involved in anxiety-like behavior.

摘要

识别与焦虑相关的基因对于阐明焦虑症的发病机制至关重要。羽田野高回避动物(HAA)和低回避动物(LAA)是根据它们在主动回避试验中的表现选育出来的近交系。HAA比LAA表现出更高水平的焦虑样行为。本研究聚焦于与焦虑样行为相关的海马体,运用微阵列分析和逆转录定量聚合酶链反应(RT-qPCR)来筛选HAA和LAA之间在海马体中差异表达的基因(实验1)。微阵列分析揭示了HAA和LAA之间498个基因表达的差异,其中21个基因与神经系统中的配体-受体相关。我们基于P值选择了9个基因并进行RT-qPCR,确定了7个在LAA中表达高于HAA的基因。我们聚焦于神经介素U受体2(Nmur2)基因,它在HAA和LAA之间表现出显著不同的表达水平。此外,我们进行了一项行为测试,通过向海马体注射神经介素U(NmU)(Nmur2的激动剂)来评估焦虑水平(实验2)。NmU处理对旷场试验和高架十字迷宫试验(焦虑的非条件反应模型)的结果没有影响。然而,在被动回避试验(焦虑的条件反应模型)中,NmU组比对照组表现出更少的焦虑样行为。这是第一项表明NmU通过海马体抑制焦虑条件反应模型的研究,表明海马体中的Nmur2可能与焦虑样行为有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ea7/12022414/21695509a006/NPR2-45-e70018-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ea7/12022414/3cf2b3bf2a74/NPR2-45-e70018-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ea7/12022414/41f48cb746fb/NPR2-45-e70018-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ea7/12022414/21695509a006/NPR2-45-e70018-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ea7/12022414/3cf2b3bf2a74/NPR2-45-e70018-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ea7/12022414/41f48cb746fb/NPR2-45-e70018-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ea7/12022414/21695509a006/NPR2-45-e70018-g002.jpg

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本文引用的文献

[1]
Administration of a Selective Antagonist for Pituitary Adenylate Cyclase-Activating Polypeptide Receptor in the Hippocampus Causes Anxiolytic Effects in the Male Rat.

Neuropsychopharmacol Rep. 2025-3

[2]
Suppressive Effects of Neuromedin U Receptor 2-Selective Peptide Agonists on Appetite and Prolactin Secretion in Mice.

ACS Med Chem Lett. 2024-2-14

[3]
Spinal Nmur2-positive Neurons Play a Crucial Role in Mechanical Itch.

J Pain. 2024-8

[4]
Fear memory regulation by the cAMP signaling pathway as an index of reexperiencing symptoms in posttraumatic stress disorder.

Mol Psychiatry. 2024-7

[5]
Recent advances in anxiety disorders: Focus on animal models and pathological mechanisms.

Animal Model Exp Med. 2023-12

[6]
Hippocampus: Molecular, Cellular, and Circuit Features in Anxiety.

Neurosci Bull. 2023-6

[7]
Effect of Escitalopram on the Number of DCX-Positive Cells and NMUR2 Receptor Expression in the Rat Hippocampus under the Condition of NPSR Receptor Blockade.

Pharmaceuticals (Basel). 2022-5-20

[8]
Possible effects of voluntary exercise intensity on anxiety-like behavior and its underlying molecular mechanisms in the hippocampus: Results from a study in Hatano rats.

Behav Brain Res. 2022-6-3

[9]
Alterations between high and low-avoidance lines of Hatano rats in learning behaviors, ultrasonic vocalizations, and histological characteristics in hippocampus and amygdala.

Physiol Behav. 2022-3-1

[10]
Anxiety and hippocampal neuronal activity: Relationship and potential mechanisms.

Cogn Affect Behav Neurosci. 2022-6

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