Cu‐Zn SOD suppresses epilepsy in pilocarpine‐treated rats and alters SCN2A/Nrf2/HO‐1 expression

Objective. Copper‐zinc superoxide dismutase (Cu‐Zn SOD) is downregulated in epilepsy, however, the role of Cu‐Zn SOD in epilepsy remains unclear. Methods. Based on the pilocarpine hydrochloride‐induced rat model of epilepsy, cortical‐striatum brain slices of rats were examined based on field excitat...

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Published in:Epileptic disorders 2022-08, Vol.24 (4), p.647-656
Main Authors: Wen, Fang, Tan, Zhi‐Gang, Xiang, Jun
Format: Article
Language:English
Subjects:
Apoptosis
Brain slice preparation
Cu‐Zn SOD
Epilepsy
Flow cytometry
Neostriatum
NRF2 protein
Nrf2/HO‐1 signalling pathway
Pilocarpine
SCN2A
Signal transduction
Sodium channels (voltage-gated)
Superoxide dismutase
Zinc
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Summary:Objective. Copper‐zinc superoxide dismutase (Cu‐Zn SOD) is downregulated in epilepsy, however, the role of Cu‐Zn SOD in epilepsy remains unclear. Methods. Based on the pilocarpine hydrochloride‐induced rat model of epilepsy, cortical‐striatum brain slices of rats were examined based on field excitatory post‐synaptic potentials. Pathological changes were observed by transmission electron microscope. Also using SH‐SY5Y cells, flow cytometry and TUNEL staining were applied to investigate cell apoptosis, and ELISA was applied to detect SOD activity. In addition, qRT‐PCR and western blot were performed to detect SCN2A/Nrf2/HO‐1 gene and protein expression levels, respectively. Results. Cu‐Zn SOD over‐expression suppressed epilepsy in vivo. In addition, Cu‐Zn SOD knockdown notably decreased SOD activity and induced apoptosis in SH‐SY5Y cells. Moreover, Cu‐Zn SOD silencing decreased the levels of SCN2A, Nrf2 and HO‐1. Lastly, Cu‐Zn SOD was shown to modulate the NaV1.2/Nrf2/HO‐1 axis in rats. Significance. In this model, Cu‐Zn SOD attenuated epilepsy and was shown to alter the expression level of proteins of the NaV1.2 /Nrf2/HO‐1 signalling pathway, indicating that Cu‐Zn SOD might be a target for the treatment of epilepsy.
ISSN:1294-9361
1950-6945
DOI:10.1684/epd.2022.1434