Sechenov Institute of Evolutionary Physiology and Biochemistry, The Russian Academy of Sciences, St. Petersburg, Russia.
Institute of Lightweight Design and Structural Biomechanics, TU Wien, Vienna, Austria.
Neurol Res. 2023 Oct;45(10):957-968. doi: 10.1080/01616412.2023.2252280. Epub 2023 Aug 29.
Hindlimb unloading (HU), widely used to simulate microgravity effects, is known to induce a stress response. However, as single-housed animals are usually used in such experiments, social isolation (SI) stress can affect experimental results. In the present study, we aimed to delineate stressful effects of 3-day HU and SI in mice.
Three animal groups, HU, SI, and group-housed (GH) control mice, were recruited. A comprehensive analysis of stress-related markers was performed using ELISA, western blotting, and immunohistochemistry.
Our results showed that blood corticosterone and activity of glucocorticoid receptors and cAMP response element-binding protein (CREB) in the hippocampus of SI and HU animals did not differ from GH control. However, SI mice demonstrated upregulation of the hippocampal corticotropin-releasing hormone (CRH), inducible NO synthase (iNOS), vesicular glutamate transporter 1 (VGLUT1), and glutamate decarboxylases 65/67 (GAD65/67) along with activation of Fos-related antigen 1 (Fra-1) in the amygdala confirming the expression of stress. In HU mice, the same increase in GAD65/67 and Fra-1 indicated the contribution of SI. The special HU effect was expressed only in neurogenesis attenuation.
Thus, our data indicated that 3-day HU could not be characterized as physiological stress, but SI stress contributed to the negative effects of HU.
后肢去负荷（HU）广泛用于模拟微重力效应，已知其会引起应激反应。然而，由于此类实验通常使用单笼饲养的动物，因此社会隔离（SI）应激会影响实验结果。在本研究中，我们旨在描绘 3 天 HU 和 SI 对小鼠的应激影响。
招募了三组动物，HU、SI 和群养（GH）对照组小鼠。使用 ELISA、western blot 和免疫组织化学法对与应激相关的标志物进行了综合分析。
我们的结果表明，SI 和 HU 动物的血液皮质酮以及海马中的糖皮质激素受体和 cAMP 反应元件结合蛋白（CREB）的活性与 GH 对照组无差异。然而，SI 小鼠表现出海马促肾上腺皮质激素释放激素（CRH）、诱导型一氧化氮合酶（iNOS）、囊泡谷氨酸转运体 1（VGLUT1）和谷氨酸脱羧酶 65/67（GAD65/67）的上调，以及杏仁核中 Fos 相关抗原 1（Fra-1）的激活，证实了应激的表达。在 HU 小鼠中，相同的 GAD65/67 和 Fra-1 增加表明了 SI 的贡献。HU 的特殊影响仅表现为神经发生减弱。
因此，我们的数据表明，3 天的 HU 不能被描述为生理应激，但 SI 应激促成了 HU 的负面效应。
