Alterations in glutamate uptake in NT2-derived neurons and astrocytes after exposure to gamma radiation.
Currently, the cellular and molecular mechanisms that underlie radiation-induced damage in the CNS are unclear. The present study began investigations of the underlying mechanism(s) for radiation-induced neurotoxicity by characterizing glutamate transport expression and function in neurons and astrocytes after exposure to gamma rays. NTera2-derived neurons and astrocytes, isolated as pure cultures, were exposed to doses of 10 cGy, 50 cGy and 2 Gy gamma rays, and transporter expression and function were assessed 3 h, 2 days and 7 days after exposure. In neurons, at 7 days after exposure, a significant increase was detected in EAAT3 after 50 cGy (P < 0.05) and a dose-dependent increase in GLT-1 expression was seen between doses of 10 and 50 cGy (P < 0.05). Functional assays of glutamate uptake revealed that neurons and astrocytes respond in a reciprocal manner after irradiation. Neurons responded to radiation exposure by increased glutamate uptake, an effect still evident at our last time (7 days) after exposure (P < 0.05). The astrocyte response to gamma radiation was an initial decrease in uptake followed by recovery to baseline levels at 2 days after exposure (P < 0.05). The observations made in this study demonstrate that neurons and astrocytes, while part of the same multifunctional unit, have distinct functional and reciprocal responses. The response in neurons appears to indicate a protracted response with potential long-term effects after irradiation.
Sanchez
Martha C
MC
Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Benitez
Abigail
A
Ortloff
Leticia
L
Green
Lora M
LM
D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000528:radiation effects*; D001692:Biological Transport / Q000528:radiation effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000528:radiation effects; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism* / Q000528:radiation effects*; D013997:Time Factors
D027322:Amino Acid Transport System X-AG; D018698:Glutamic Acid