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中缝正中区的多巴胺能细胞调节雄性小鼠的社会行为。

The Dopaminergic Cells in the Median Raphe Region Regulate Social Behavior in Male Mice.

作者信息

Chaves Tiago, Török Bibiána, Fazekas Csilla Lea, Correia Pedro, Sipos Eszter, Várkonyi Dorottya, Tóth Zsuzsanna E, Dóra Fanni, Dobolyi Árpád, Zelena Dóra

机构信息

Institute of Physiology, Medical School, Centre for Neuroscience, Szentágothai Research Centre, University of Pécs, H7624 Pécs, Hungary.

Laboratory of Behavioral and Stress Studies, Institute of Experimental Medicine, H1083 Budapest, Hungary.

出版信息

Int J Mol Sci. 2024 Apr 13;25(8):4315. doi: 10.3390/ijms25084315.

Abstract

According to previous studies, the median raphe region (MRR) is known to contribute significantly to social behavior. Besides serotonin, there have also been reports of a small population of dopaminergic neurons in this region. Dopamine is linked to reward and locomotion, but very little is known about its role in the MRR. To address that, we first confirmed the presence of dopaminergic cells in the MRR of mice (immunohistochemistry, RT-PCR), and then also in humans (RT-PCR) using healthy donor samples to prove translational relevance. Next, we used chemogenetic technology in mice containing the Cre enzyme under the promoter of the dopamine transporter. With the help of an adeno-associated virus, designer receptors exclusively activated by designer drugs (DREADDs) were expressed in the dopaminergic cells of the MRR to manipulate their activity. Four weeks later, we performed an extensive behavioral characterization 30 min after the injection of the artificial ligand (Clozapine-N-Oxide). Stimulation of the dopaminergic cells in the MRR decreased social interest without influencing aggression and with an increase in social discrimination. Additionally, inhibition of the same cells increased the friendly social behavior during social interaction test. No behavioral changes were detected in anxiety, memory or locomotion. All in all, dopaminergic cells were present in both the mouse and human samples from the MRR, and the manipulation of the dopaminergic neurons in the MRR elicited a specific social response.

摘要

根据先前的研究,中缝正中区域(MRR)对社会行为有显著贡献。除了血清素外,该区域也有少量多巴胺能神经元的报道。多巴胺与奖赏和运动有关,但对其在中缝正中区域的作用知之甚少。为了解决这个问题,我们首先通过免疫组织化学、逆转录-聚合酶链反应(RT-PCR)在小鼠的中缝正中区域证实了多巴胺能细胞的存在,然后利用健康供体样本通过RT-PCR在人类中也证实了这一点,以证明其转化相关性。接下来,我们在多巴胺转运体启动子下含有Cre酶的小鼠中使用化学遗传学技术。在腺相关病毒的帮助下,仅由设计药物激活的设计受体(DREADDs)在中缝正中区域的多巴胺能细胞中表达,以操纵它们的活性。四周后,在注射人工配体(氯氮平N-氧化物)30分钟后,我们进行了广泛的行为特征分析。刺激中缝正中区域的多巴胺能细胞会降低社会兴趣,而不影响攻击性,并增加社会辨别力。此外,抑制相同的细胞会增加社交互动测试中的友好社交行为。在焦虑、记忆或运动方面未检测到行为变化。总而言之,在小鼠和人类样本的中缝正中区域均存在多巴胺能细胞,并且对中缝正中区域多巴胺能神经元的操纵引发了特定的社会反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7c/11050709/ad10a77eb112/ijms-25-04315-g001.jpg

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