Glausier Jill R
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Adv Exp Med Biol. 2025;1477:105-137. doi: 10.1007/978-3-031-89525-8_5.
The human brain is an energetically costly organ, consuming 20-25% of all biochemical energy produced in the body, despite comprising only 2-3% of total body mass. Most energy in the brain is consumed to support synaptic neurotransmission, which is the primary means of neuron-to-neuron communication between. This energy is in the form of adenosine triphosphate (ATP), and within neural cells, nearly all ATP is produced by mitochondria via the process of oxidative phosphorylation (OXPHOS). To ensure that ATP is readily available, mitochondria are trafficked to areas of greater energy use, such as neuronal synapses. The balance between energetic supply and synaptic communication is essential for proper brain functioning. This chapter begins with a brief introduction to key features of neuronal synapses and mitochondrial energy production in the cerebral cortex. Next, the tight and bidirectional coupling of neuronal synaptic activity and mitochondrial OXPHOS is examined from functional, ultrastructural, and molecular perspectives. The effects of brain and non-brain organ system perturbations on synaptic-mitochondrial coupling are then examined within the context of (1) primary brain disorders, such as schizophrenia and bipolar disorder, and (2) primary peripheral disorders, such as diabetes and obesity. Finally, a discussion of potential intervention strategies that may restore neural communication and mitochondrial bioenergetics, within the framework of the brain-body connection, is provided.
人类大脑是一个能量消耗巨大的器官，尽管仅占体重的2%至3%，却消耗了身体产生的所有生物化学能量的20%至25%。大脑中的大部分能量用于支持突触神经传递，这是神经元之间通信的主要方式。这种能量以三磷酸腺苷（ATP）的形式存在，在神经细胞内，几乎所有的ATP都是由线粒体通过氧化磷酸化（OXPHOS）过程产生的。为了确保随时都能获得ATP，线粒体被运输到能量消耗较大的区域，如神经元突触。能量供应与突触通信之间的平衡对于大脑的正常功能至关重要。本章首先简要介绍大脑皮质中神经元突触和线粒体能量产生的关键特征。接下来，从功能、超微结构和分子角度研究神经元突触活动与线粒体OXPHOS之间紧密的双向耦合。然后在（1）精神分裂症和双相情感障碍等原发性脑部疾病以及（2）糖尿病和肥胖症等原发性外周疾病的背景下，研究大脑和非大脑器官系统紊乱对突触-线粒体耦合的影响。最后，在脑-体连接的框架内，讨论了可能恢复神经通信和线粒体生物能量学的潜在干预策略。
