Lactate-mediated glia-neuronal signaling in the mammalian brain (Nature comm, 2014, 5: 3284)

報告日期: 2014/11/14
報告時間: 3:10/4:00
報告學生: 鄭向帆(以英文報告)
講評老師: 簡伯武
附件下載: 下載[1449-1412238698-1.pdf] 

Lactate-mediated glia-neuronal signaling in the mammalian brain

Nat Commun. 2014;5:3284.

F. Tang1,*, S. Lane1,*, A. Korsak2, J.F.R. Paton1, A.V. Gourine2, S. Kasparov1 & A.G. Teschemacher1

          Date: 2014.11.14                                               Place: Room 602

          Time: 15:10                                                       Reporter: Cheng, Hsiang-Fan

          Commentator: Gean, Po-Wu, Ph.D.                      Advisor: Yang, Bei-Chang, Ph.D.



In recent decades, more and more studies show that astrocytes are able to modulate neuronal synaptic transmission via various glio-transmitters. Both neuronal and astrocytic inputs affect noradrenergic neuron at locus coeruleus (LC) and influent the norepinephrine (NE) release. However, the signaling molecule between astrocyte and neuron is not known. The lactate shuttle hypothesis proposed that neurons take up L-lactate secreted by astrocytes via monocarboxylate transporters and use it as metabolic substrate. It has also been demonstrated that pharmacological intervention of lactate would affect long-term potentiation and memory, but the mechanism is suspected as interfering of neuron energy metabolism. Combining above two questions, the authors hypothesized that lactate may directly participate in glial-neuronal signaling. They stimulated astrocytes that were engineered to express optogenetic actuators with light and measured electrophysiological responses of LC neurons using patch clamp. The releases of NE were determined directly with fast-scan cyclic voltammetry. These experiments revealed that L-lactate released from astrocytes acted as an excitatory stimulant to LC neurons and then triggered the releases of NE. In vivo experiments demonstrated that microinjection of L-lactate into LC increased arterial blood pressure and EEG frequency similar to those of glutamate effects. Despite the receptors of L-lactate are not identified, the L-lactate mediated stimulation was independent from action potential and lactate uptake mechanism. The L-lactate induced signaling pathway in neuron was mediated by cAMP and PKA. In conclusion, this paper provides a novel idea that L-lactate acts as a glio-transmitter in addition to the role of energy supplier.