Mason Shayne
Centre for Human Metabolomics, North-West University Potchefstroom, South Africa.
Front Neurosci. 2017 Feb 2;11:43. doi: 10.3389/fnins.2017.00043. eCollection 2017.
Understanding brain energy metabolism-neuroenergetics-is becoming increasingly important as it can be identified repeatedly as the source of neurological perturbations. Within the scientific community we are seeing a shift in paradigms from the traditional neurocentric view to that of a more dynamic, integrated one where astrocytes are no longer considered as being just supportive, and activated microglia have a profound influence. Lactate is emerging as the "good guy," contrasting its classical "bad guy" position in the now superseded medical literature. This review begins with the evolution of the concept of "lactate shuttles"; goes on to the recent shift in ideas regarding normal neuroenergetics (homeostasis)-specifically, the astrocyte-neuron lactate shuttle; and progresses to covering the metabolic implications whereby homeostasis is lost-a state of allostasis, and the function of microglia. The role of lactate, as a substrate and shuttle, is reviewed in light of allostatic stress, and beyond-in an acute state of allostatic stress in terms of physical brain trauma, and reflected upon with respect to persistent stress as allostatic overload-neurodegenerative diseases. Finally, the recently proposed astrocyte-microglia lactate shuttle is discussed in terms of chronic neuroinflammatory infectious diseases, using tuberculous meningitis as an example. The novelty extended by this review is that the directionality of lactate, as shuttles in the brain, in neuropathophysiological states is emerging as crucial in neuroenergetics.
了解大脑能量代谢——神经能量学——正变得越来越重要，因为它一再被确认为神经功能紊乱的根源。在科学界，我们正目睹一种范式转变，从传统的以神经为中心的观点转向一种更具动态性、综合性的观点，在这种观点中，星形胶质细胞不再仅仅被视为起支持作用，而活化的小胶质细胞具有深远影响。乳酸正成为“好人”，这与它在现已被取代的医学文献中经典的“坏人”形象形成对比。本综述首先介绍“乳酸穿梭”概念的演变；接着阐述关于正常神经能量学（内稳态）观念的最新转变——具体而言，星形胶质细胞 - 神经元乳酸穿梭；进而探讨内稳态丧失——一种非稳态状态的代谢影响以及小胶质细胞的功能。鉴于非稳态应激以及在急性非稳态应激状态下（如物理性脑损伤），乳酸作为底物和穿梭物的作用进行了综述，并就作为非稳态过载的持续性应激——神经退行性疾病进行了思考。最后，以结核性脑膜炎为例，讨论了最近提出的星形胶质细胞 - 小胶质细胞乳酸穿梭在慢性神经炎性感染性疾病中的情况。本综述的新颖之处在于，乳酸作为大脑中穿梭物在神经病理生理状态下的方向性在神经能量学中正变得至关重要。
