Nrf2 is predominantly expressed in hippocampal neurons in a rat model of temporal lobe epilepsy

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background: Drug resistance is a particular problem in patients with temporal lobe epilepsy, where seizures originate mainly from the hippocampus. Many of these epilepsies are acquired conditions following an insult to the brain such as a prolonged seizure. Such conditions are characterized by pathophysiological mechanisms including massive oxidative stress that synergistically mediate the secondary brain damage, contributing to the development of epilepsy. The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged in recent years as an attractive therapeutic approach targeting to upregulate the antioxidative defenses in the cell, to ameliorate the oxidative stress-induced damage. Thus, it is important to understand the characteristics of Nrf2 activation during epileptogenesis and epilepsy. Here, we studied the temporal, regional, and cell-type specific expression of Nrf2 in the brain, in a rat model of temporal lobe epilepsy. Results: Early after status-epilepticus, Nrf2 is mainly activated in the hippocampus and maintained during the whole period of epileptogenesis. Only transient expression of Nrf2 was observed in the cortex. Nevertheless, the expression of several Nrf2 antioxidant target genes was increased within 24 h after status-epilepticus in both the cortex and the hippocampus. We demonstrated that after status-epilepticus in rats, Nrf2 is predominantly expressed in neurons in the CA1 and CA3 regions of the hippocampus, and only astrocytes in the CA1 increase their Nrf2 expression. Conclusions: In conclusion, our data identify previously unrecognized spatial and cell-type dependent activation of Nrf2 during epilepsy development, highlighting the need for a time-controlled, and cell-type specific activation of the Nrf2 pathway for mediating anti-oxidant response after brain insult, to modify the development of epilepsy.

Original languageAmerican English
Article number3
JournalCell and Bioscience
Volume13
Issue number1
DOIs
StatePublished - 4 Jan 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

Keywords

  • Antioxidants
  • Kainic Acid
  • Nrf2
  • Oxidative stress
  • Status epilepticus

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