Jara Claudia, Torres Angie K, Park-Kang Han S, Sandoval Lisette, Retamal Claudio, Gonzalez Alfonso, Ricca Micaela, Valenzuela Sebastián, Murphy Michael P, Inestrosa Nibaldo C, Tapia-Rojas Cheril
Laboratory of Neurobiology of Aging, Centro Científico y Tecnológico de Excelencia Ciencia & Vida, Fundación Ciencia & Vida, Avenida del Valle Norte 725, Huechuraba, Santiago, 8580702, Chile.
Facultad de Medicina y Ciencia, Universidad San Sebastián, Lota 2465, Santiago, 7510157, Chile.
Neurotox Res. 2025 Jan 8;43(1):3. doi: 10.1007/s12640-024-00726-y.
Mitochondria produces energy through oxidative phosphorylation (OXPHOS), maintaining calcium homeostasis, survival/death cell signaling mechanisms, and redox balance. These mitochondrial functions are especially critical for neurons. The hippocampus is crucial for memory formation in the brain, which is a process with high mitochondrial function demand. Loss of hippocampal function in aging is related to neuronal damage, where mitochondrial impairment is critical. Synaptic and mitochondrial dysfunction are early events in aging; both are regulated reciprocally and contribute to age-associated memory loss together. We previously showed that prolonged treatment with Curcumin or Mitoquinone (MitoQ) improves mitochondrial functions in aged mice, exerting similar neuroprotective effects. Curcumin has been described as an anti-inflammatory and antioxidant compound, and MitoQ is a potent antioxidant directly targeting mitochondria; however, whether Curcumin exerts a direct impact on the mitochondria is unclear. In this work, we study whether Curcumin could have a mechanism similar to MitoQ targeting the mitochondria. We utilized hippocampal slices of 4-6-month-old C57BL6 mice to assess the cellular changes induced by acute Curcumin treatment ex-vivo compared to MitoQ. Our results strongly suggest that both compounds improve the synaptic structure, oxidative state, and energy production in the hippocampus. Nevertheless, Curcumin and MitoQ modify mitochondrial function differently; MitoQ improves the mitochondrial bioenergetics state, reducing ROS production and increasing ATP generation. In contrast, Curcumin reduces mitochondrial calcium levels and prevents calcium overload related to mitochondrial swelling. Thus, Curcumin is described as a new regulator of mitochondrial calcium homeostasis and could be used in pathological events involving calcium deregulation and excitotoxicity, such as aging and neurodegenerative diseases.
线粒体通过氧化磷酸化（OXPHOS）产生能量，维持钙稳态、细胞存活/死亡信号机制以及氧化还原平衡。这些线粒体功能对神经元尤为关键。海马体对大脑中的记忆形成至关重要，而这一过程对线粒体功能的需求很高。衰老过程中海马体功能的丧失与神经元损伤有关，其中线粒体损伤至关重要。突触和线粒体功能障碍是衰老过程中的早期事件；两者相互调节，共同导致与年龄相关的记忆丧失。我们之前表明，用姜黄素或线粒体醌（MitoQ）长期治疗可改善衰老小鼠的线粒体功能，发挥类似的神经保护作用。姜黄素被描述为一种抗炎和抗氧化化合物，而MitoQ是一种直接靶向线粒体的强效抗氧化剂；然而，姜黄素是否对线粒体有直接影响尚不清楚。在这项工作中，我们研究姜黄素是否可能具有与MitoQ类似的靶向线粒体的机制。我们利用4 - 6月龄C57BL6小鼠的海马切片，与MitoQ相比，评估体外急性姜黄素处理诱导的细胞变化。我们的结果强烈表明，这两种化合物都能改善海马体中的突触结构、氧化状态和能量产生。然而，姜黄素和MitoQ对线粒体功能的影响不同；MitoQ改善线粒体生物能量状态，减少活性氧产生并增加ATP生成。相比之下，姜黄素降低线粒体钙水平，防止与线粒体肿胀相关的钙超载。因此，姜黄素被描述为线粒体钙稳态的新调节剂，可用于涉及钙失调和兴奋性毒性的病理事件，如衰老和神经退行性疾病。
