Integrated kinetic, genetic, and thermodynamic investigation of brain energy metabolism in neurons and astrocytes

Neuro-glial interactions are important for normal functioning of the brain as well as brain energy metabolism. There are two major working models ? in the classical view, both neurons and astrocytes can utilize glucose as the energy source through oxidative metabolism, whereas in the astrocyte-neuron lactate shuttle hypothesis (ANLSH) it is the astrocyte which can consume glucose through anaerobic glycolysis to pyruvate and then to lactate, and this lactate is secreted to the extracellular space to be taken up by the neuron for further oxidative degradation. In the integrated kinetic and genetic part of the study, energy metabolism in neurons and astrocytes were analyzed whether the ANLSH model can provide an advantage to either cell type in terms of supplying the energy demand. This experimentation-supported in silico modeling results showed that under both normoxic and hypoxic conditions in a given time period ANLSH model does indeed provide the neuron with more ATP than in the classical view. In the thermodynamic part of the study, exergy analysis was applied from the perspective of a neuron, and exergetic efficiency of ATP production in the neuron is assessed with two competing models (classical and ANLSH), seperately. Therefore, it is predicted that the ANLSH model is energetically more favorable to the neuron. Also, unsteady exergy loss of neuron under dynamic stress conditions (normoxic, hypoxic, glucose starvation and excess glucose concentration) was analyzed. According to the analysis result, it is emphasized that not only the work potential, but also the rate of exergy loss of the cell is highest under excess glucose concentration and lowest under glucose starvation condition.