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慢性应激导致大鼠脑线粒体呼吸链活性的性别特异性和结构特异性改变。

Chronic Stress Causes Sex-Specific and Structure-Specific Alterations in Mitochondrial Respiratory Chain Activity in Rat Brain.

机构信息

Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcellos, 2600, anexo, Porto Alegre, Rio Grande Do Sul, 90035-003, Brazil.

Department of Cellular Biology, Universidade de Brasília, Brasilia, Distrito Federal, Brazil.

出版信息

Neurochem Res. 2017 Nov;42(11):3331-3340. doi: 10.1007/s11064-017-2375-9. Epub 2017 Sep 14.

DOI:10.1007/s11064-017-2375-9
PMID:28913592
Abstract

Chronic restraint stress (CRS) induces a variety of changes in brain function, some of which are mediated by glucocorticoids. The response to stress occurs in a sex-specific way, and may include mitochondrial and synaptic alterations. The synapse is highly dependent on mitochondrial energy supply, and when mitochondria become dysfunctional, they orchestrate cell death. This study aimed to investigate the CRS effects on mitochondrial respiratory chain activity, as well as mitochondrial potential and mass in cell body and synapses using hippocampus, cortex and striatum of male and female rats. Rats were divided into non-stressed (control) and stressed group (CRS during 40 days). Results showed that CRS increased complex I-III activity in hippocampus. We also observed an interaction between CRS and sex in the striatal complex II activity, since CRS induced a reduction in complex II activity in males, while in females this activity was increased. Also an interaction was observed between stress and sex in cortical complex IV activity, since CRS induced increased activity in females, while it was reduced in males. Glucocorticoid receptor (GR) content in cortex and hippocampus was sexually dimorphic, with female rats presenting higher levels compared to males. No changes were observed in GR content, mitochondrial potential or mass of animals submitted to CRS. It was concluded that CRS induced changes in respiratory chain complex activities, and some of these changes are sex-dependent: these activities are increased in the striatal mitochondria by CRS protocol mainly in females, while in males it is decreased.

摘要

慢性束缚应激(CRS)会引起大脑功能的多种变化,其中一些是由糖皮质激素介导的。应激反应以性别特异性的方式发生,可能包括线粒体和突触的改变。突触高度依赖于线粒体的能量供应,当线粒体功能失调时,它们会协调细胞死亡。本研究旨在探讨 CRS 对雄性和雌性大鼠海马体、皮质和纹状体线粒体呼吸链活性、线粒体膜电位和质量的影响。大鼠分为非应激(对照)和应激组(40 天内 CRS)。结果表明,CRS 增加了海马体中复合物 I-III 的活性。我们还观察到 CRS 和性别之间在纹状体复合物 II 活性上存在相互作用,因为 CRS 诱导雄性复合物 II 活性降低,而在雌性中则增加。皮质中复合物 IV 活性也观察到应激和性别之间的相互作用,因为 CRS 诱导雌性活性增加,而雄性活性降低。皮质和海马体中的糖皮质激素受体(GR)含量存在性别二态性,雌性大鼠的水平高于雄性。CRS 并未改变动物的 GR 含量、线粒体膜电位或质量。综上所述,CRS 诱导了呼吸链复合物活性的变化,其中一些变化是性别依赖性的:CRS 方案主要在雌性纹状体线粒体中增加这些活性,而在雄性中则降低。

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