Pegueros-Maldonado Rogelio, Fuentes-Ibañez Antonio, Monroy Mónica M, Gutiérrez Oscar A, Serafín Norma, Pech-Pool Santiago M, Díaz-Muñoz Mauricio, Quirarte Gina L
Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico.
Facultad de Química, Universidad Autónoma de Querétaro, Querétaro, Mexico.
Front Mol Neurosci. 2024 Dec 4;17:1495027. doi: 10.3389/fnmol.2024.1495027. eCollection 2024.
Stressful experiences form stronger memories due to enhanced neural plasticity mechanisms linked to glucocorticoid hormones (cortisol in humans, corticosterone in rats). Among other neural structures, the dorsal striatum plays a role in the corticosterone-induced consolidation of stressful memories, particularly in the cued water maze task. Neural plasticity is related to mitochondrial activity due to the relevance of energy production and signaling mechanisms for functional and morphological neuronal adaptations. Corticosterone has been shown to enhance brain mitochondrial activity by activating glucocorticoid receptors. In this context, striatum functions are susceptible to change in relation to mitochondrial responses. Based on this evidence, we hypothesized that training in the cued water maze would induce an increase in corticosterone levels and mitochondrial activity (mitochondrial membrane potential and calcium content) in the dorsal striatum, and that these adaptations might be related to memory consolidation of the task. We used an ELISA assay to evaluate plasma and striatal corticosterone levels; mitochondrial activity was determined with the florescent probes MitoTracker Red (mitochondrial membrane potential) and Rhod-2 (calcium content) in brain slices containing the dorsal striatum of rats trained in the cued water maze and euthanized at different times after training (0.5, 1.5, or 6.0 h). We also analyzed the effect of post-training inhibition of striatal mitochondrial activity by OXPHOS complex 1 inhibitor rotenone, on the consolidation of the cued water maze task. We found that cued water maze training induced an increase in corticosterone levels and a time-dependent elevation of mitochondrial membrane potential and mitochondrial calcium content in the dorsal striatum. Unexpectedly, rotenone administration facilitated the retention test. Altogether, our results suggest that enhanced mitochondrial activity in the dorsal striatum is relevant for cued water maze consolidation. The increase in mitochondrial activity was contextually associated with an elevation of corticosterone in plasma and the dorsal striatum. Additionally, our swimming groups also showed an increase in mitochondrial activity in the dorsal striatum, but with a different pattern, which could suggest a differential functional adaptation in this structure.
由于与糖皮质激素（人类中的皮质醇，大鼠中的皮质酮）相关的神经可塑性机制增强，应激经历会形成更强的记忆。在其他神经结构中，背侧纹状体在皮质酮诱导的应激记忆巩固中起作用，特别是在提示性水迷宫任务中。由于能量产生以及功能和形态神经元适应的信号机制的相关性，神经可塑性与线粒体活性有关。已表明皮质酮通过激活糖皮质激素受体来增强脑线粒体活性。在这种情况下，纹状体功能易受线粒体反应变化的影响。基于这些证据，我们假设在提示性水迷宫中的训练会导致背侧纹状体中皮质酮水平和线粒体活性（线粒体膜电位和钙含量）增加，并且这些适应性变化可能与该任务的记忆巩固有关。我们使用酶联免疫吸附测定（ELISA）来评估血浆和纹状体皮质酮水平；用荧光探针MitoTracker Red（线粒体膜电位）和Rhod-2（钙含量）测定在提示性水迷宫中训练并在训练后不同时间（0.5、1.5或6.0小时）安乐死的大鼠背侧纹状体脑片中的线粒体活性。我们还分析了在训练后用氧化磷酸化复合物1抑制剂鱼藤酮抑制纹状体线粒体活性对提示性水迷宫任务巩固的影响。我们发现提示性水迷宫训练导致皮质酮水平升高以及背侧纹状体中线粒体膜电位和线粒体钙含量随时间升高。出乎意料的是，给予鱼藤酮促进了记忆保持测试。总之，我们的结果表明背侧纹状体中线粒体活性增强与提示性水迷宫巩固有关。线粒体活性的增加与血浆和背侧纹状体中皮质酮的升高在背景上相关。此外，我们的游泳组在背侧纹状体中也显示出线粒体活性增加，但模式不同，这可能表明该结构存在不同的功能适应性。
