Emotional behaviors as well as the hippocampal reelin expression in C57BL/6N male mice chronically treated with corticosterone

IF 3.3 3区 心理学 Q1 BEHAVIORAL SCIENCES
Daisuke Ibi , Genki Nakasai , Masahito Sawahata , Rika Takaba , Maho Kinoshita , Kiyofumi Yamada , Masayuki Hiramatsu
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Abstract

Depression is a common psychiatric disorder affecting around 300 million people worldwide. Serum cortisol and glucocorticoid levels in humans are reportedly higher in patients with depression compared to controls. Furthermore, rodents repeatedly treated with exogenous corticosterone (CORT), a glucocorticoid in rodents, exhibit deficits in emotional behaviors. To confirm the availability of mice with chronic CORT treatment as an animal model of depression, we investigated the effect of chronic CORT treatment on depression-like behavioral and neuropathological phenotypes in C57BL/6N male mice. Behavioral studies showed depression- and anxiety-like behaviors in mice treated with CORT compared with control mice in the forced-swim and elevated-plus maze tests. Additionally, treated mice represented anhedonia and social behavior impairments in the sucrose preference and social interaction tests, respectively. Brains of depression patients have altered expression of reelin, an extracellular matrix protein involved in neuronal development and function. Likewise, in the present study, mice with chronic CORT treatment also exhibited reelin downregulation in cells of the hippocampus. Hence, we investigated therapeutic effects of reelin supplementation on CORT-induced behavioral abnormalities in mice. Microinjections of recombinant reelin protein into the hippocampus did not rescue behavioral deficits in mice with chronic CORT treatment. These results suggest that C57BL/6N male mice chronically treated with CORT are a suitable animal depression model, in which depressive behaviors may occur independently of the alternation of hippocampal Reelin expression.

慢性皮质酮治疗的C57BL/6N雄性小鼠的情绪行为和海马reelin表达。
抑郁症是一种常见的精神疾病,影响着全世界约3亿人。据报道,抑郁症患者的血清皮质醇和糖皮质激素水平高于对照组。此外,反复使用外源性皮质酮(CORT)(啮齿类动物的一种糖皮质激素)治疗的啮齿类动物表现出情绪行为缺陷。为了证实慢性CORT治疗小鼠作为抑郁症动物模型的可用性,我们研究了慢性CORT处理对C57BL/6N雄性小鼠抑郁样行为和神经病理学表型的影响。行为研究显示,在强迫游泳和提升+迷宫测试中,与对照小鼠相比,接受CORT治疗的小鼠表现出抑郁和焦虑样行为。此外,在蔗糖偏好和社会互动测试中,接受治疗的小鼠分别表现出快感缺乏和社会行为障碍。抑郁症患者的大脑改变了reelin的表达,reelin是一种参与神经元发育和功能的细胞外基质蛋白。同样,在本研究中,接受慢性CORT治疗的小鼠海马细胞中也表现出reelin下调。因此,我们研究了补充reelin对CORT诱导的小鼠行为异常的治疗作用。在接受慢性CORT治疗的小鼠中,向海马微量注射重组reelin蛋白并不能挽救其行为缺陷。这些结果表明,长期用CORT治疗的C57BL/6N雄性小鼠是一种合适的动物抑郁模型,其中抑郁行为可能独立于海马Reelin表达的改变而发生。
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来源期刊
CiteScore
6.40
自引率
2.80%
发文量
122
审稿时长
38 days
期刊介绍: Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.
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