• Neuroscience · Sep 2016

    Sodium valproate prevents radiation-induced injury in hippocampal neurons via activation of the Nrf2/HO-1 pathway.

    • Guixiang Liao, Rong Li, Xiaohui Chen, Wenqing Zhang, Shasha Du, and Yawei Yuan.
    • Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, China; Department of Radiation Oncology, Shenzhen people's Hospital, Second Clinical Medicine College of Jinan University, China; Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515 China.
    • Neuroscience. 2016 Sep 7; 331: 40-51.

    PurposeTo investigate the neuroprotective role of sodium valproate (VPA) in a hippocampal neuronal cell line (HT22) and the hippocampus of zebrafish after exposure to radiation.MethodsWe investigated whether VPA could protect HT22 hippocampal neurons and the hippocampus of zebrafish from radiation-induced injury. We measured the generation of reactive oxygen species (ROS), the mitochondrial membrane potential, the levels of glutathione (GSH) and malondialdehyde (MDA), and the activity of superoxide dismutase (SOD). The expression of nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was also measured. The cognitive behavior of the zebrafish was evaluated 1month after radiation exposure.ResultsVPA treatment improved the survival rate (300 mg/kg body weight (BW) VPA: 76.67%; 100 mg/kg BW VPA: 56.7%) of zebrafish 1 month after exposure to a lethal dose of whole-body irradiation (P<0.01). VPA treatment decreased the ROS generation (P<0.01), decreased the MDA levels (P<0.01), increased the GSH levels (P<0.01) and increased the SOD activity (P<0.01). VPA treatment activated the Nrf2/HO-1 pathway, increased the nuclear translocation of Nrf2 and increased the mRNA (P<0.01) and protein expression of HO-1 to prevent radiation-induced neuronal injury. SiRNA knockdown of the Nrf2 gene prevented the VPA-induced attenuation of radiation injury in the HT22 neuronal cells that was found in the control cells (40.09±1.76% vs. 41.14±1.09%, P>0.05). VPA also improved the zebrafish cognitive behavior after radiation-induced neuronal injury as measured by the exploration test (control 5.74±1.42min vs. radiation therapy 16.39±4.03min vs. radiation therapy plus VPA 7.18±1.79min, P<0.05).ConclusionsROS generation after radiation exposure contributes to DNA damage in the zebrafish brain. VPA inhibits ROS generation by activating the Nrf2/HO-1 pathway, which improves cognitive behavior following radiation-induced neuronal injury.Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

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