Nature Neuroscience has a nice special focus on glia and disease. The featured reviews and perspective articles discuss multiple aspects of neuron-glia interactions and their role in disease. The reason why I am highlighting this collection here is that I have the feeling that this field could potentially be a nice playground for systems biology.
A similar complexity is seen in the events underlying ischemic glutamate release. Loss of cellular ATP levels impairs the function of the Na+-K+ ATPase and thus disrupts ionic gradients. The resulting depolarization leads to a large increase in extracellular glutamate that is amplified by positive feedback, ultimately resulting in neuronal death by excitotoxicity. Astrocytes may contribute to increased extracellular glutamate levels via direct vesicular glutamate release and vesicular ATP release that in turn activates glutamate-permeable P2X receptors. Glutamate reuptake is normally carried out by five high-affinity sodium-dependent glutamate transporters. Disruption of transmembrane potential and of ionic gradients can cause transporter reversal thus further contributing to glutamate release. This depends in turn on the intracellular glutamate concentration which is much higher in astrocytes than neurons, determining the relative kinetic of neuronal and astrocytic reuptake/release as the ischemic perturbations progress. Further details are visible on Figure 3 from Rossi et al (2007):
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