PUBLICATION
Sodium valproate prevents radiation-induced injury in hippocampal neurons via activation of the Nrf2/HO-1 pathway
- Authors
- Liao, G., Li, R., Chen, X., Zhang, W., Du, S., Yuan, Y.
- ID
- ZDB-PUB-160622-1
- Date
- 2016
- Source
- Neuroscience 331: 40-51 (Journal)
- Registered Authors
- Chen, Xiaohui
- Keywords
- Cognitive damage, Ionizing irradiation, Reactive oxygen species, Sodium valproate
- MeSH Terms
-
- Animals
- Cell Nucleus/drug effects
- Cell Nucleus/metabolism
- Cell Nucleus/radiation effects
- Drug Evaluation, Preclinical
- Signal Transduction/drug effects
- Signal Transduction/radiation effects
- NF-E2-Related Factor 2/metabolism
- Cognition/drug effects
- Cognition/physiology
- Cognition/radiation effects
- Fish Proteins/metabolism
- Oxidative Stress/drug effects
- Oxidative Stress/physiology
- Oxidative Stress/radiation effects
- Valproic Acid/pharmacology*
- Zebrafish
- Hippocampus/drug effects*
- Hippocampus/metabolism
- Hippocampus/radiation effects
- Radiation-Protective Agents/pharmacology*
- Heme Oxygenase-1/metabolism
- Neuroprotective Agents/pharmacology*
- Cell Survival/drug effects
- Cell Survival/physiology
- Cell Survival/radiation effects
- Cell Line
- Neurons/drug effects*
- Neurons/metabolism
- Neurons/radiation effects
- Radiation Injuries, Experimental/metabolism
- Radiation Injuries, Experimental/prevention & control*
- Membrane Proteins/metabolism
- RNA, Messenger/metabolism
- PubMed
- 27328419 Full text @ Neuroscience
Citation
Liao, G., Li, R., Chen, X., Zhang, W., Du, S., Yuan, Y. (2016) Sodium valproate prevents radiation-induced injury in hippocampal neurons via activation of the Nrf2/HO-1 pathway. Neuroscience. 331:40-51.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping