[Interaction between neurons and astrocytes involved in brain regulatory function as assessed by in vitro brain...

In the recent decade of brain research, one of the most interesting findings is the significance of the active neuronal-glial interaction. It is no exaggeration to say that astrocytes in the central nervous system have an important role, participating in the regulation of neuronal functions. For instance, the fate of brain neurotransmitters, especially amino acids, following their release by neurons, is to be mainly inactivated by uptake via specific high-affinity transport systems into not only neuronal cells but also astrocytes, rather than by extracellular enzymatic degradation. These uptake mechanisms in astrocytes are very important for maintaining brain neuronal function under the low energy condition. In our research using the in vitro brain ischemia model, it was demonstrated that the neuronal death induced by excessive amounts of glutamate (Glu) under low energy conditions (hypoglycemia, hypoxia, particularly acidosis) is caused by dysfunctions of astrocyte Glu uptake and glutamine (Gln) output systems, and neural death can be modulated by the number of surrounding astrocytes in the cultured brain cells. Moreover, the neuronal dysfunction induced by excessive amounts of Glu was enhanced by a blocker of Glu uptake into astrocytes rather than an antagonist of Gln synthetase, which mainly exists in the astrocytes. During dysfunctions of astrocytes induced by acidosis, sustained increases of NO metabolites, ammonia and cytokines were produced. These biological substances may regulate the functions of neuronal cells and astrocytes. Thus, the balance of astrocyte-neuronal cells can maintain the brain neuronal homeostasis.