Cellular and metabolic origins of flavoprotein autofluorescence in the cerebellar cortex in vivo.
Cellular and metabolic origins of flavoprotein autofluorescence in the cerebellar cortex in vivo.
复制标题
体内小脑皮质黄素蛋白自发荧光的细胞和代谢起源
DOI：
10.1007/s12311-011-0278-x
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发表时间：
2011-09
期刊：
影响因子：
3.5
通讯作者：
Ebner, Timothy J.
中科院分区：
文献类型：
--
作者：
Reinert, Kenneth C.;Gao, Wangcai;Chen, Gang;Wang, Xinming;Peng, Yu-Ping;Ebner, Timothy J.
黄素蛋白自发荧光成像是一种内在的线粒体信号，已被证明可用于监测神经元活动。在小脑皮层中，平行纤维刺激引起类似光束的反应，包括最初的、短持续时间的荧光增加（光束光阶段），随后是较长持续时间的荧光减少（光束暗阶段）。由于分子层抑制，还引起荧光减少的矢状旁带。先前的研究表明，光束光相是由神经元的氧化代谢引起的。本研究进一步研究了体内黄素蛋白信号的代谢和细胞起源，测试了暗相由神经胶质细胞激活介导的假设，并且抑制带反映了神经元中黄素蛋白氧化的减少和糖酵解的增加。阻断突触后离子型和代谢型谷氨酸受体消除了光束亮相和旁矢状带，而不改变光束暗相。添加谷氨酸转运蛋白阻断剂可减少暗相。用乳酸（或丙酮酸）代替葡萄糖或在沐浴介质中添加乳酸可以消除光束暗相并减少抑制带，而不影响光相。阻断单羧酸转运蛋白消除了光束上的暗相并增加了亮相。这些结果证实，光束光阶段主要是由于神经元氧化代谢增加所致。他们还表明，光束暗相涉及神经胶质细胞中糖酵解的激活，导致乳酸的产生并转移到神经元。神经元中的氧化积聚导致抑制带荧光的减少。这些发现为星形胶质细胞-神经元乳酸穿梭假说提供了强有力的体内支持。
Flavoprotein autofluorescence imaging, an intrinsic mitochondrial signal, has proven useful for monitoring neuronal activity. In the cerebellar cortex, parallel fiber stimulation evokes a beam-like response consisting of an initial, short-duration increase in fluorescence (on-beam light phase) followed by a longer duration decrease (on-beam dark phase). Also evoked are parasagittal bands of decreased fluorescence due to molecular layer inhibition. Previous work suggests that the on-beam light phase is due to oxidative metabolism in neurons. The present study further investigated the metabolic and cellular origins of the flavoprotein signal in vivo, testing the hypotheses that the dark phase is mediated by glia activation and the inhibitory bands reflect decreased flavoprotein oxidation and increased glycolysis in neurons. Blocking postsynaptic ionotropic and metabotropic glutamate receptors abolished the on-beam light phase and the parasagittal bands without altering the on-beam dark phase. Adding glutamate transporter blockers reduced the dark phase. Replacing glucose with lactate (or pyruvate) or adding lactate to the bathing media abolished the on-beam dark phase and reduced the inhibitory bands without affecting the light phase. Blocking monocarboxylate transporters eliminated the on-beam dark phase and increased the light phase. These results confirm that the on-beam light phase is due primarily to increased oxidative metabolism in neurons. They also show that the on-beam dark phase involves activation of glycolysis in glia resulting in the generation of lactate that is transferred to neurons. Oxidative savings in neurons contributes to the decrease in fluorescence characterizing the inhibitory bands. These findings provide strong in vivo support for the astrocyte–neuron lactate shuttle hypothesis.
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