Sodium valproate prevents radiation-induced injury in hippocampal neurons via activation of the Nrf2/HO-1 pathway. (7th September 2016)

• Record Type: Journal Article
• Authors: Liao, Guixiang; Li, Rong; Chen, Xiaohui; Zhang, Wenqing; Du, Shasha; Yuan, Yawei
• Is Part Of: Neuroscience. Volume 331(2016)
• Page Start: 40
• Page End: 51
• Publication Date: 2016-09-07
• Subjects: BW body weight -- GSH glutathione -- GSK3 glucose synthase kinase-3 -- HDAC histone deacetylase -- HO-1 heme oxygenase-1 -- MDA malondialdehyde -- ROS reactive oxygen species -- siRNAs short interfering RNAs -- SOD superoxide dismutase; sodium valproate -- ionizing irradiation -- reactive oxygen species -- cognitive damage; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.06.019
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Reactive oxygen species induced by radiation can cause injury in the hippocampus of zebrafish and the HT22 cells. Sodium valproate can improve the cognitive function by attenuating oxidative stress induced-injury after radiation. Sodium valproate can provide neuroprotective effect by activating Nrf2/HO-1 pathway. Abstract: Purpose: To investigate the neuroprotective role of sodium valproate (VPA) in a hippocampal neuronal cell line (HT22) and the hippocampus of zebrafish after exposure to radiation. Methods: We 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 1 month after radiation exposure. Results: VPA 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 ± 1.42 min vs. radiation therapy 16.39 ± 4.03 min vs. radiation therapy plus VPA 7.18 ± 1.79 min, P < 0.05). Conclusions: ROS 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.