Nrf2 is expressed more extensively in neurons than in astrocytes following an acute epileptic seizure in rats

Sereen Sandouka, Aseel Saadi, Rhoda Olowe, Prince Kumar Singh, Tawfeeq Shekh-Ahmad*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The modulation of the nuclear factor erythroid 2-like 2 (Nrf2) activity has been reported to be implicated in the pathology of various neurological disorders, including epilepsy. Previous studies have demonstrated that Nrf2 is activated in the post-status epilepticus rat model; however, the spatiotemporal as well as cell type-specific expression of Nrf2 following brief epileptic seizures remains unclear. Here, we evaluated how an acute epileptic seizure affected the expression of Nrf2 and its downstream genes in the rats' cortex and the hippocampus up to 1 week following the induced seizure. We found that after a pentylenetetrazol-induced seizure, Nrf2 significantly increased at 24 h at the mRNA level and 3 h at the protein level in the cortex. In the hippocampus, the Nrf2 mRNA level peaked at 3 h after the seizure, and no significant changes were observed in the protein level. Interestingly, the mRNA level of Nrf2 downstream genes peaked at 3–6 h after seizure in both the cortex and the hippocampus. A significant increase in the expression of Nrf2 was observed in the neuronal population of CA1 and CA3 regions of the hippocampus, as well as in the cortex. Moreover, we observed no change in the co-localization of Nrf2 with astrocytes neither in the cortex nor in CA1 and CA3. Our results revealed that following a brief acute epileptic seizure, the expression of Nrf2 and its downstream genes is transiently increased and peaked at early timepoints after the seizure predominantly in the hippocampus, and this expression is restricted to the neuronal population. (Figure presented.)

Original languageAmerican English
Pages (from-to)550-562
Number of pages13
JournalJournal of Neurochemistry
Volume165
Issue number4
DOIs
StatePublished - May 2023

Bibliographical note

Funding Information:
The authors are thankful to The Neubauer Family Foundation for their generous support in our research. We also acknowledge the David R. Bloom Center for Pharmacy for financial support. This work is abstracted from the PhD thesis of Ms. Sereen Sandouka in a partial fulfillment for the requirements of a PhD degree at The Hebrew University of Jerusalem.

Publisher Copyright:
© 2023 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

Keywords

  • Nrf2
  • antioxidants
  • epilepsy
  • oxidative stress
  • pentylenetetrazol
  • seizure

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