Wu Zuotian, Wang Gaohua, Xiao Ling, Wei Yanyan, Wang Huiling, Zhou Lin, Sun Limin
Department of Psychiatry, Renmin Hospital of Wuhan University, Jiefang Road No. 238, Wuhan, 430060, China.
Department of Psychiatry, Renmin Hospital of Wuhan University, Jiefang Road No. 238, Wuhan, 430060, China.
Brain Res Bull. 2020 Sep;162:261-270. doi: 10.1016/j.brainresbull.2020.06.015. Epub 2020 Jul 6.
Depressive-like behaviors occur at 24 h after lipopolysaccharide (LPS) injection, but whether the animals have resilience has not been reported. This study is to explore the existence of resilience in the LPS-induced acute depressive-like behaviors and its biological changes in the neuroprotection and microtubule dynamics. The behavioral tests of Sprague-Dawley male rats, including body weight (BW), sucrose preference test (SPT), forced swimming test (FST) and open field test (OFT), which are used to explore depressive and anxiety-like behaviors, were detected at 24 h after intraperitoneal injection of LPS. In the LPS-induced depression group, body weight and sucrose preference index in SPT were decreased, the immobility time in FST was increased, total distance, time in central zone and frequency of rearing in OFT were decreased. However, there was not any difference in behavioral phenotypes between the resilient animals and the saline control group. The activity of collapsing response mediator protein 2 (CRMP2), which is related to neuronal plasticity and neuroprotection, was increased in resilient rats. The brain-derived neurotrophic factor (BDNF) mRNA expression was also increased. The ratio of Tyr/Acet-tubulin in hippocampus, which is an important marker of microtubule dynamics, was increased without alpha-tubulin. In addition, the expression of CRMP2 and alpha-tubulin in dentate gyrus (DG) region increased in resilient animals, but not in CA1 and CA3 regions. This study firstly confirms the phenomenon of resilience in the LPS-induced acute depressive-like behaviors animal model. CRMP2 neuroprotection and microtubule dynamics in hippocampus are enhanced in this phenomenon of resilience, which may functionally contribute to resilience but need further research.
脂多糖(LPS)注射后24小时会出现类似抑郁的行为,但动物是否具有恢复力尚未见报道。本研究旨在探讨LPS诱导的急性类似抑郁行为中恢复力的存在及其在神经保护和微管动力学方面的生物学变化。在腹腔注射LPS后24小时,对Sprague-Dawley雄性大鼠进行行为测试,包括体重(BW)、蔗糖偏好试验(SPT)、强迫游泳试验(FST)和旷场试验(OFT),以探讨类似抑郁和焦虑的行为。在LPS诱导的抑郁组中,SPT中的体重和蔗糖偏好指数降低,FST中的不动时间增加,OFT中的总距离、中央区域停留时间和竖毛频率降低。然而,恢复力动物与生理盐水对照组之间的行为表型没有差异。在恢复力大鼠中,与神经元可塑性和神经保护相关的塌陷反应介质蛋白2(CRMP2)的活性增加。脑源性神经营养因子(BDNF)mRNA表达也增加。海马体中Tyr/Acet-微管蛋白的比例增加,这是微管动力学的一个重要标志物,且α-微管蛋白无变化。此外,恢复力动物齿状回(DG)区域中CRMP2和α-微管蛋白的表达增加,但CA1和CA3区域未增加。本研究首次证实了LPS诱导的急性类似抑郁行为动物模型中存在恢复力现象。在这种恢复力现象中,海马体中的CRMP2神经保护和微管动力学增强,这可能在功能上有助于恢复力,但仍需进一步研究。