Caddye Edward, Pineau Julien, Reyniers Joshua, Ronen Itamar, Colasanti Alessandro
Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, University of Sussex, Falmer BN1 9RR, UK.
Department of Clinical Neuroscience, Brighton and Sussex Medical School, University of Sussex, Falmer BN1 9RR, UK.
Antioxidants (Basel). 2023 Aug 22;12(9):1656. doi: 10.3390/antiox12091656.
Alterations in neurometabolism and mitochondria are implicated in the pathophysiology of psychiatric conditions such as mood disorders and schizophrenia. Thus, developing objective biomarkers related to brain mitochondrial function is crucial for the development of interventions, such as central nervous system penetrating agents that target brain health. Lactate, a major circulatory fuel source that can be produced and utilized by the brain and body, is presented as a theranostic biomarker for neurometabolic dysfunction in psychiatric conditions. This concept is based on three key properties of lactate that make it an intriguing metabolic intermediate with implications for this field: Firstly, the lactate response to various stimuli, including physiological or psychological stress, represents a quantifiable and dynamic marker that reflects metabolic and mitochondrial health. Second, lactate concentration in the brain is tightly regulated according to the sleep-wake cycle, the dysregulation of which is implicated in both metabolic and mood disorders. Third, lactate universally integrates arousal behaviours, pH, cellular metabolism, redox states, oxidative stress, and inflammation, and can signal and encode this information via intra- and extracellular pathways in the brain. In this review, we expand on the above properties of lactate and discuss the methodological developments and rationale for the use of functional magnetic resonance spectroscopy for in vivo monitoring of brain lactate. We conclude that accurate and dynamic assessment of brain lactate responses might contribute to the development of novel and personalized therapies that improve mitochondrial health in psychiatric disorders and other conditions associated with neurometabolic dysfunction.
神经代谢和线粒体的改变与情绪障碍和精神分裂症等精神疾病的病理生理学有关。因此，开发与脑线粒体功能相关的客观生物标志物对于开发干预措施至关重要，例如针对脑健康的中枢神经系统穿透剂。乳酸是一种主要的循环燃料来源，可由大脑和身体产生和利用，它被视为精神疾病中神经代谢功能障碍的一种诊疗生物标志物。这一概念基于乳酸的三个关键特性，这些特性使其成为该领域一个引人关注的代谢中间体：首先，乳酸对各种刺激（包括生理或心理压力）的反应代表了一个可量化的动态标志物，反映了代谢和线粒体健康状况。其次，大脑中的乳酸浓度根据睡眠-觉醒周期受到严格调节，而这种调节失调与代谢和情绪障碍都有关。第三，乳酸普遍整合了觉醒行为、pH值、细胞代谢、氧化还原状态、氧化应激和炎症，并可通过大脑中的细胞内和细胞外途径传递和编码这些信息。在这篇综述中，我们详细阐述了乳酸的上述特性，并讨论了使用功能磁共振波谱对脑乳酸进行体内监测的方法学进展和原理。我们得出结论，对脑乳酸反应进行准确和动态的评估可能有助于开发新的个性化疗法，改善精神疾病和其他与神经代谢功能障碍相关疾病中的线粒体健康状况。
