Madrer Nimrod, Perera Nirma D, Uccelli Nonthué A, Abbondanza Alice, Andersen Jens V, Carsana Emma Veronica, Demmings Matthew D, Fernandez Regina F, de Fragas Matheus Garcia, Gbadamosi Ismail, Kulshrestha Divita, Lima-Filho Ricardo A S, Marian Oana C, Markussen Kia H, McGovern Andrew J, Neal Elliott S, Sarkar Sukanya, Šimončičová Eva, Soto-Verdugo Jazmín, Yandiev Sozerko, Fernández-Moncada Ignacio
The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.
J Neurochem. 2025 Jun;169(6):e70084. doi: 10.1111/jnc.70084.
Neural networks are responsible for processing sensory stimuli and driving the synaptic activity required for brain function and behavior. This computational capacity is expensive and requires a steady supply of energy and building blocks to operate. Importantly, the neural networks are composed of different cell populations, whose metabolic profiles differ between each other, thus endowing them with different metabolic capacities, such as, for example, the ability to synthesize specific metabolic precursors or variable proficiency to manage their metabolic waste. These marked differences likely prompted the emergence of diverse intercellular metabolic interactions, in which the shuttling and cycling of specific metabolites between brain cells allows the separation of workload and efficient control of energy demand and supply within the central nervous system. Nevertheless, our knowledge about brain bioenergetics and the specific metabolic adaptations of neural cells still warrants further studies. In this review, originated from the Fourth International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Schmerlenbach, Germany (2022), we describe and discuss the specific metabolic profiles of brain cells, the intercellular metabolic exchanges between these cells, and how these bioenergetic activities shape synaptic function and behavior. Furthermore, we discuss the potential role of faulty brain metabolic activity in the etiology and progression of Alzheimer's disease, Parkinson disease, and Amyotrophic lateral sclerosis. We foresee that a deeper understanding of neural networks metabolism will provide crucial insights into how higher-order brain functions emerge and reveal the roots of neuropathological conditions whose hallmarks include impaired brain metabolic function.
神经网络负责处理感觉刺激，并驱动大脑功能和行为所需的突触活动。这种计算能力代价高昂，需要稳定的能量供应和构建模块来维持运行。重要的是，神经网络由不同的细胞群体组成，它们的代谢特征彼此不同，从而赋予它们不同的代谢能力，例如，合成特定代谢前体的能力或处理代谢废物的不同熟练程度。这些显著差异可能促使了多种细胞间代谢相互作用的出现，其中特定代谢物在脑细胞之间的穿梭和循环使得中枢神经系统内的工作负荷得以分担，并能有效控制能量需求和供应。然而，我们对大脑生物能量学以及神经细胞的特定代谢适应性的了解仍有待进一步研究。在这篇源于第四届国际神经化学学会（ISN）和《神经化学杂志》（JNC）旗舰学校于德国施默伦巴赫举行（2022年）的综述中，我们描述并讨论了脑细胞的特定代谢特征、这些细胞之间的细胞间代谢交换，以及这些生物能量活动如何塑造突触功能和行为。此外，我们还讨论了大脑代谢活动异常在阿尔茨海默病、帕金森病和肌萎缩侧索硬化症的病因和进展中的潜在作用。我们预计，对神经网络代谢的更深入理解将为高阶大脑功能如何出现提供关键见解，并揭示以大脑代谢功能受损为特征的神经病理状况的根源。
