Radiation-induced glutamate transport alterations in neuron-astrocyte coupling

Exposure of the central nervous system (CNS) to ionizing radiation is known to result in behavioral, cognitive, and motor deficits---effects similar to those seen in many neurodegenerative disorders. Neurons and astrocytes, two principal cell types in the brain, coexist as an interdependent metabolic unit via the neurotransmitter glutamate. Disruption of this metabolic coupling would have widespread effects within the CNS, therefore it is hypothesized that ionizing radiation impairs glutamate transport and metabolism, and increases oxidative stress, ultimately impairing neuron-astrocyte coupling. We propose to investigate the mechanists and determine the impetus for radiation-induced neurotoxicity by measuring the temporal sequence of glutamate transport dysfunction and oxidative stress following radiation. To achieve this objective, we utilized the NTera2/D1 cell line which was induced to differentiate into neurons and astrocytes. Neuron and astrocyte cultures were then exposed to ionizing radiation and changes in glutamate transport and antioxidant levels were measured to ascertain the temporal relationship between glutamate dysfunction and cellular antioxidant capacity. We examined alterations in glutamate transport dysfunction as an underlying mechanism of radiation-induced neurotoxicity. In particular, we examined specific cellular and molecular factors of glutamate transport dysfunction in order to elucidate a specific mechanism of radiation-induced neuronal damage. Thus, we were able to observe acute functional changes at a cellular and molecular level, thereby allowing us to ascertain the probability that radiation exposure will result in long-term neurodegenerative effects.