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急性冷应激对小鼠神经行为学的影响及其模型的建立

Effect of Acute Cold Stress on Neuroethology in Mice and Establishment of Its Model.

作者信息

Hu Yajie, Liu Yang, Li Shize

机构信息

National Experimental Teaching Demonstration Center of Animal Medicine Foundation, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China.

出版信息

Animals (Basel). 2022 Oct 4;12(19):2671. doi: 10.3390/ani12192671.

Abstract

Cold environment is an inevitable stress source for humans and livestock in cold areas, which easily induce a cold stress response and then cause a series of abnormal changes in energy metabolism, neuroendocrine system, behavior and emotion. Homeostasis is maintained by the unified regulation of the autonomic nervous system, endocrine system, metabolism and behavior under cold exposure. Behavior is an indispensable part of the functional regulation of the body to respond to environmental changes. At present, the behavioral changes caused by cold exposure are unclear or even chaotic due to the difficulty of defining cold stress. Therefore, this study aims to systematically observe the changes in spontaneous movement, exploratory behavior and anxiety of mice under different intensity cold exposure and summarize the characteristics and behavior traits combined with relevant blood physiological indexes under corresponding conditions. Mice models of cold stress with different intensities were established (cold exposure gradients were 22 °C, 16 °C, 10 °C and 4 °C, and time gradients of each temperature were 2 h, 4 h, 6 h, 8 h, 10 h and 12 h). After the corresponding cold exposure treatment, mice immediately carried out the open field test(OFT) and elevated plus maze test (PMT) to evaluate their spontaneous movement, exploratory behavior and anxiety. Subsequently, blood samples were collected and used for the determination of corticosterone (Cort), corticotropin-releasing hormone (CRH), epinephrine (E), norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) by enzyme-linked immunosorbent assay (ELISA). Spontaneous movement of mice increased under 22 °C cold exposure, but their exploration behavior did not significantly change, and their anxiety improved at the initial stage. The spontaneous movement and anxiety of mice increased in the initial stage and decreased in the later stage under cold exposure at 16, 10 and 4 °C and the exploratory behavior was inhibited. The hypothalamic-pituitary-adrenal (HPA) axis and locus coeruleus-noradrenergic (LC/NE) system were activated by cold stress and fluctuated with different intensities of cold exposure. Meanwhile, serum DA increased, and 5-HT was the opposite under different intensities of cold exposure. In conclusion, mild acute cold exposure promoted the spontaneous movement, increased exploratory behavior and improved anxiety. As the intensity of cold exposure increases, cold exposure had a negative effect on spontaneous movement, exploratory behavior and emotion. The physiological basis of these behavioral and emotional changes in mice under different intensity cold stimulation is the fluctuation of Cort, CRH, E, NE, DA and 5-HT.

摘要

寒冷环境是寒冷地区人类和家畜不可避免的应激源,容易引发冷应激反应,进而导致能量代谢、神经内分泌系统、行为和情绪出现一系列异常变化。在寒冷暴露条件下,通过自主神经系统、内分泌系统、代谢和行为的统一调节来维持体内平衡。行为是机体功能调节以应对环境变化不可或缺的一部分。目前,由于难以界定冷应激,寒冷暴露引起的行为变化尚不清楚甚至混乱。因此,本研究旨在系统观察不同强度寒冷暴露下小鼠的自发活动、探究行为和焦虑的变化,并结合相应条件下的相关血液生理指标总结其特征和行为特点。建立了不同强度冷应激小鼠模型(寒冷暴露梯度为22℃、16℃、10℃和4℃,每个温度的时间梯度为2小时、4小时、6小时、8小时、10小时和12小时)。经过相应的寒冷暴露处理后,小鼠立即进行旷场试验(OFT)和高架十字迷宫试验(EPMT),以评估其自发活动、探究行为和焦虑情况。随后,采集血样,采用酶联免疫吸附测定法(ELISA)测定皮质酮(Cort)、促肾上腺皮质激素释放激素(CRH)、肾上腺素(E)、去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)。在22℃寒冷暴露下小鼠的自发活动增加,但其探究行为无明显变化,且焦虑在初期有所改善。在16℃、10℃和4℃寒冷暴露下,小鼠的自发活动和焦虑在初期增加,后期减少,且探究行为受到抑制。冷应激激活了下丘脑-垂体-肾上腺(HPA)轴和蓝斑-去甲肾上腺素能(LC/NE)系统,并随寒冷暴露强度的不同而波动。同时,在不同强度寒冷暴露下血清DA升高,而5-HT则相反。总之,轻度急性寒冷暴露促进了自发活动,增加了探究行为,改善了焦虑。随着寒冷暴露强度的增加,寒冷暴露对自发活动、探究行为和情绪产生负面影响。不同强度寒冷刺激下小鼠这些行为和情绪变化的生理基础是Cort、CRH、E、NE、DA和5-HT的波动。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44d3/9559653/7792b7030541/animals-12-02671-g001.jpg

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