Forsyth R, Fray A, Boutelle M, Fillenz M, Middleditch C, Burchell A
Department of Child Health, Royal Victoria Infirmary, University of Newcastle upon Tyne, UK.
Dev Neurosci. 1996;18(5-6):360-70. doi: 10.1159/000111429.
The present paper examines the possible role of astrocytes in the delivery of glycogen-derived glucose for neuronal metabolism. Such a process would require astrocytic expression of glucose-6-phosphatase. The degree and significance of brain expression of glucose-6-phosphatase (EC 3.1.3.9) has been a subject of controversy. Published immunohistochemical data are consistent with expression of glucose-6-phosphatase by astrocytes, both in vivo and in vitro. In this paper additional confirmation of the expression of glucose-6-phosphatase mRNA in rat brain is presented. Although cultured astrocytes demonstrate glucose-6-phosphatase activity in vitro under assay conditions, there is very limited in vitro evidence that this activity confers a glucose-export capacity on astrocytes. Under most conditions in vitro, lactate export predominates, however this may relate to aspects of the in vitro phenotype. Data relating to astrocytic glucose and lactate export are considered in the context of hypotheses of trafficking by astrocytes of substrates for neuronal metabolism, hypotheses that imply and require compartmentation of these substances, in contrast with current formulations of glucose transport into and within brain that imply no glucose compartmentation. Microdialysis studies of the properties of the brain extracellular fluid (ECF) glucose pool in the freely moving rat were performed seeking evidence of glucose compartmentation. Results of these studies do imply compartmentalisation of brain glucose, and are consistent with a model envisaging the majority of glucose reaching the neuron via the astrocytic intracellular space and the ECF. In addition, such studies provide evidence that rises in ECF glucose concentration are not the direct result of local recruitment of cerebral blood flow, but suggest the influence of intermediate, astrocyte-based mechanisms. Astrocytic glucose-6-phosphatase may permit astrocytes to modulate the trans-astrocytic flux of glucose to adjacent neurons in response to signals reflecting increased neuronal demand.
本文探讨了星形胶质细胞在为神经元代谢提供糖原衍生葡萄糖过程中可能发挥的作用。这样一个过程需要星形胶质细胞表达葡萄糖-6-磷酸酶。脑内葡萄糖-6-磷酸酶（EC 3.1.3.9）的表达程度及意义一直存在争议。已发表的免疫组化数据表明，无论是在体内还是体外，星形胶质细胞均可表达葡萄糖-6-磷酸酶。本文提供了大鼠脑内葡萄糖-6-磷酸酶mRNA表达的更多证据。虽然培养的星形胶质细胞在体外检测条件下表现出葡萄糖-6-磷酸酶活性，但体外证据非常有限，表明这种活性赋予星形胶质细胞葡萄糖输出能力。在大多数体外条件下，乳酸输出占主导，但这可能与体外表型的某些方面有关。在关于星形胶质细胞转运神经元代谢底物的假说背景下，考虑了与星形胶质细胞葡萄糖和乳酸输出相关的数据，这些假说暗示并需要对这些物质进行分隔，这与目前关于葡萄糖进入脑内及在脑内转运的说法不同，后者认为不存在葡萄糖分隔。对自由活动大鼠脑细胞外液（ECF）葡萄糖池特性进行了微透析研究，以寻找葡萄糖分隔的证据。这些研究结果确实暗示了脑葡萄糖的分隔，并且与设想大多数葡萄糖通过星形胶质细胞内空间和ECF到达神经元的模型一致。此外，此类研究提供证据表明，ECF葡萄糖浓度升高并非局部脑血流量募集的直接结果，而是提示存在基于星形胶质细胞的中间机制的影响。星形胶质细胞的葡萄糖-6-磷酸酶可能使星形胶质细胞能够根据反映神经元需求增加的信号，调节葡萄糖向相邻神经元的跨星形胶质细胞通量。
