Sickmann Helle M, Walls Anne B, Schousboe Arne, Bouman Stephan D, Waagepetersen Helle S
Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark.
J Neurochem. 2009 May;109 Suppl 1:80-6. doi: 10.1111/j.1471-4159.2009.05915.x.
The involvement of brain glycogen in sustaining neuronal activity has previously been demonstrated. However, to what extent energy derived from glycogen is consumed by astrocytes themselves or is transferred to the neurons in the form of lactate for oxidative metabolism to proceed is at present unclear. The significance of glycogen in fueling glutamate uptake into astrocytes was specifically addressed in cultured astrocytes. Moreover, the objective was to elucidate whether glycogen derived energy is important for maintaining glutamatergic neurotransmission, induced by repetitive exposure to NMDA in co-cultures of cerebellar neurons and astrocytes. In the astrocytes it was shown that uptake of the glutamate analogue D-[3H]aspartate was impaired when glycogen degradation was inhibited irrespective of the presence of glucose, signifying that energy derived from glycogen degradation is important for the astrocytic compartment. By inhibiting glycogen degradation in co-cultures it was evident that glycogen provides energy to sustain glutamatergic neurotransmission, i.e. release and uptake of glutamate. The relocation of glycogen derived lactate to the neuronal compartment was investigated by employing d-lactate, a competitive substrate for the monocarboxylate transporters. Neurotransmitter release was affected by the presence of d-lactate indicating that glycogen derived energy is important not only in the astrocytic but also in the neuronal compartment.
脑糖原参与维持神经元活动这一点此前已得到证实。然而，目前尚不清楚糖原产生的能量在多大程度上被星形胶质细胞自身消耗，或者是以乳酸的形式转移到神经元中以进行氧化代谢。在培养的星形胶质细胞中专门探讨了糖原在为谷氨酸摄取到星形胶质细胞中提供能量方面的意义。此外，目的是阐明糖原衍生的能量对于维持在小脑神经元和星形胶质细胞共培养物中反复暴露于NMDA所诱导的谷氨酸能神经传递是否重要。在星形胶质细胞中发现，无论葡萄糖是否存在，当糖原降解受到抑制时，谷氨酸类似物D-[3H]天冬氨酸的摄取都会受损，这表明糖原降解产生的能量对星形胶质细胞区室很重要。通过抑制共培养物中的糖原降解，很明显糖原提供能量以维持谷氨酸能神经传递，即谷氨酸的释放和摄取。通过使用d-乳酸（一种单羧酸转运体的竞争性底物）来研究糖原衍生的乳酸向神经元区室的重新分布。d-乳酸的存在影响神经递质的释放，表明糖原衍生的能量不仅在星形胶质细胞区室而且在神经元区室中都很重要。
