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催产素抑制皮质酮诱导的原代海马神经元凋亡。

Oxytocin Inhibits Corticosterone-induced Apoptosis in Primary Hippocampal Neurons.

机构信息

Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.

Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.

出版信息

Neuroscience. 2018 May 21;379:383-389. doi: 10.1016/j.neuroscience.2018.03.025. Epub 2018 Mar 27.

Abstract

Stress is an adaptive and coordinated response to endogenous or exogenous stressors that pose an unpleasant and aversive threat to an individual's homeostasis and wellbeing. Glucocorticoids, corticosterone (CORT) in rodents and cortisol in humans, are adrenal steroids which are released in response to stressful stimuli. Although they help individuals to cope with stress, their overexposure in animals has been implicated in hippocampal dysfunction and neuronal loss. Oxytocin (OT) plays an active role in adaptive stress-related responses and protects hippocampal synaptic plasticity and memory during stress. In this study, we showed that OT protects primary mouse hippocampal neurons from CORT-induced apoptosis. OT receptors (OTR) were expressed in primary mouse hippocampal neurons and glial cells. CORT induced apoptosis in hippocampal neurons, but had no effect on apoptosis in glial cells. OT inhibited CORT-induced apoptosis in primary hippocampal neurons. OT was unable to protect primary hippocampal neurons prepared from OTR KO mice from CORT-induced apoptosis. These results indicate that OT has inhibitory effects on CORT-induced neuronal death in primary hippocampal neurons via acting on OTR. The findings suggest a therapeutic potential of OT in the treatment of stress-related disorders.

摘要

压力是一种适应和协调的反应,针对的是对内源或外源应激源的反应,这些应激源对内个体的体内平衡和健康构成了不愉快和厌恶的威胁。糖皮质激素、啮齿动物中的皮质酮(CORT)和人类中的皮质醇,是对应激刺激释放的肾上腺类固醇。虽然它们有助于个体应对压力,但它们在动物中的过度暴露已被牵连到海马功能障碍和神经元丧失。催产素(OT)在适应应激相关反应中发挥积极作用,并在应激期间保护海马突触可塑性和记忆。在这项研究中,我们表明 OT 可防止原代小鼠海马神经元受到 CORT 诱导的凋亡。OT 受体(OTR)在原代小鼠海马神经元和神经胶质细胞中表达。CORT 诱导海马神经元凋亡,但对神经胶质细胞凋亡没有影响。OT 抑制原代海马神经元中的 CORT 诱导凋亡。OT 无法保护来自 OTR KO 小鼠的原代海马神经元免受 CORT 诱导的凋亡。这些结果表明,OT 通过作用于 OTR,对原代海马神经元中的 CORT 诱导的神经元死亡具有抑制作用。这些发现表明 OT 在治疗应激相关疾病方面具有治疗潜力。

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