Li Song, Wang Che, Wang Wei, Dong Huiping, Hou Peng, Tang Yiyuan
Laboratory for Brain and Mind, Institute of Neuroinformatics, Dalian University of Technology, Dalian, 116024, China.
Life Sci. 2008 Apr 23;82(17-18):934-42. doi: 10.1016/j.lfs.2008.02.010. Epub 2008 Mar 4.
Exposure to chronic stress in rodents and psychosocial stress in humans has been shown to alter cognitive functions and has been linked to the pathophysiology of mood disorders. The purpose of the present study was to investigate effects and possible mechanisms of a chronic mild stress (CMS) procedure on cognitive behaviors in Swiss albino mice using the object recognition test (ORT) and object location test (OLT). Results showed that CMS exposure impaired cognitive performance and produced amnesia of acquired information in both ORT and OLT. Furthermore, the cognitive impairment was coexistent with increased plasma levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), as well as with enhanced plasma levels of corticosterone (CORT), corticotrophin-releasing hormone (CRH) and adrenocorticotrophic hormone (ACTH). In addition, severe neuronal cell damage was found, as bromodeoxyuridine (BrdU) positive cells and the expression of brain derived neurotrophic factor (BDNF) in dentate gyrus (DG) of hippocampus were decreased after 5 weeks CMS procedure. Taken together, these findings indicated that CMS exposure-induced impairment of cognitive behaviors might be attributed to the stress-related alterations in brain homeostasis that were reflected in changes in the neuroimmune and neuroendocrine systems as well as in neurogenesis.
在啮齿动物中暴露于慢性应激以及在人类中经历心理社会应激已被证明会改变认知功能，并与情绪障碍的病理生理学相关联。本研究的目的是使用物体识别测试（ORT）和物体位置测试（OLT）来研究慢性轻度应激（CMS）程序对瑞士白化小鼠认知行为的影响及其可能机制。结果表明，CMS暴露损害了认知表现，并在ORT和OLT中导致对已获取信息的遗忘。此外，认知障碍与血浆中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平升高以及血浆中皮质酮（CORT）、促肾上腺皮质激素释放激素（CRH）和促肾上腺皮质激素（ACTH）水平升高同时存在。此外，发现了严重的神经元细胞损伤，因为在进行5周CMS程序后，海马齿状回（DG）中的溴脱氧尿苷（BrdU）阳性细胞和脑源性神经营养因子（BDNF）的表达降低。综上所述，这些发现表明，CMS暴露诱导的认知行为损害可能归因于脑内稳态中与应激相关的改变，这些改变反映在神经免疫和神经内分泌系统以及神经发生的变化中。
