Ishikawa Yuka, Kitaoka Shiho, Kawano Yuko, Ishii Shinichi, Suzuki Tomohide, Wakahashi Kanako, Kato Taro, Katayama Yoshio, Furuyashiki Tomoyuki
Division of Pharmacology, Graduate School of Medicine, Kobe University, Kobe, Japan.
Sumitomo Dainippon Pharma Co., Ltd., Osaka, Japan.
Br J Pharmacol. 2021 Feb;178(4):827-844. doi: 10.1111/bph.15203. Epub 2020 Aug 6.
Inflammation has been associated with stress-related mental disturbances. Rodent studies have reported that blood-borne cytokines are crucial for stress-induced changes in emotional behaviours. However, the roles and regulation of leukocytes in chronic stress remain unclear.
Adult male C57BL/6N mice were subjected to repeated social defeat stress (R-SDS) with two protocols which differed in stress durations, stress cycles, and housing conditions, followed by the social interaction test. The numbers of leukocyte subsets in the bone marrow, spleen, and blood were determined by flow cytometry shortly after or several days after R-SDS. These leukocyte changes were studied in two strains of mice with different stress susceptibility, C57BL/6N and BALB/c mice.
R-SDS with both protocols similarly induced social avoidance in C57BL/6N mice. In the bone marrow, neutrophils and monocytes were increased, and T cells, B cells, NK cells, and dendritic cells were decreased with both protocols. In the blood, neutrophils and monocytes were increased with both protocols, whereas T cells, B cells, NK cells, and dendritic cells were decreased with one of these. Neutrophils and monocytes were also increased in the spleen. Changes in the bone marrow and increased levels of circulating neutrophils were maintained for 6 days after R-SDS. BALB/c mice showed greater social avoidance and increase in circulating neutrophils than C57BL/6N mice.
In two strains of mice, chronic stress induced neutrophil mobilization and its maintenance. These effects were strain-related and may contribute to the pathology of mental illness.
This article is part of a themed issue on Neurochemistry in Japan. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.4/issuetoc.
炎症与应激相关的精神障碍有关。啮齿动物研究报告称，血源性细胞因子对于应激诱导的情绪行为变化至关重要。然而，白细胞在慢性应激中的作用和调节仍不清楚。
成年雄性C57BL/6N小鼠接受两种方案的重复社会挫败应激（R-SDS），这两种方案在应激持续时间、应激周期和饲养条件方面有所不同，随后进行社会互动测试。在R-SDS后不久或几天后，通过流式细胞术测定骨髓、脾脏和血液中白细胞亚群的数量。在两种具有不同应激易感性的小鼠品系C57BL/6N和BALB/c小鼠中研究了这些白细胞变化。
两种方案的R-SDS均同样诱导C57BL/6N小鼠出现社会回避行为。在骨髓中，两种方案均使中性粒细胞和单核细胞增加，而T细胞、B细胞、NK细胞和树突状细胞减少。在血液中，两种方案均使中性粒细胞和单核细胞增加，而其中一种方案使T细胞、B细胞、NK细胞和树突状细胞减少。脾脏中的中性粒细胞和单核细胞也增加。R-SDS后6天，骨髓变化和循环中性粒细胞水平升高得以维持。BALB/c小鼠比C57BL/6N小鼠表现出更大的社会回避行为和循环中性粒细胞增加。
在两种小鼠品系中，慢性应激诱导中性粒细胞动员及其维持。这些效应与品系相关，可能导致精神疾病的病理变化。
本文是日本关于神经化学的主题问题的一部分。要查看本部分的其他文章，请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.4/issuetoc。
