Figure 7
Proposed model demonstrating the key role of P5CS in maintaining glutamate homeostasis during acute METH exposure. The schematic model shows presynaptic and postsynaptic neurons along with astrocytes and highlights the pathways involved in glutamate homeostasis in the brain. The left panel depicts the sequestration of excess glutamate in the neuron for proline biosynthesis during acute METH exposure. Specifically, METH-induced enhancement of P5CS expression is associated with utilization of glutamate for proline synthesis, thus maintaining glutamate homeostasis. Whereas, the right panel describes that depletion of P5CS blocks the proline synthetic arm from glutamate and abrogates glutamate sequestration for proline biosynthesis. This metabolic disruption results in an increased levels of glutamate that could be detrimental for the neurons.
