Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Daytime-Restricted Feeding Ameliorates Oxidative Stress by Increasing NRF2 Transcriptional Factor in the Rat Hippocampus after Pilocarpine-Induced Acute Seizure Model

Version 1 : Received: 19 September 2023 / Approved: 20 September 2023 / Online: 21 September 2023 (08:23:19 CEST)

A peer-reviewed article of this Preprint also exists.

Mercado-Gómez, O.F.; Arriaga-Ávila, V.S.; Vega-García, A.; Orozco-Suarez, S.; Pérez-Koldenkova, V.; Camarillo-Sánchez, J.J.; Álvarez-Herrera, M.; Guevara-Guzmán, R. Daytime-Restricted Feeding Ameliorates Oxidative Stress by Increasing NRF2 Transcriptional Factor in the Rat Hippocampus in the Pilocarpine-Induced Acute Seizure Model. Brain Sci. 2023, 13, 1442. Mercado-Gómez, O.F.; Arriaga-Ávila, V.S.; Vega-García, A.; Orozco-Suarez, S.; Pérez-Koldenkova, V.; Camarillo-Sánchez, J.J.; Álvarez-Herrera, M.; Guevara-Guzmán, R. Daytime-Restricted Feeding Ameliorates Oxidative Stress by Increasing NRF2 Transcriptional Factor in the Rat Hippocampus in the Pilocarpine-Induced Acute Seizure Model. Brain Sci. 2023, 13, 1442.

Abstract

Seizure-mediated oxidative stress is a crucial mechanism in the pathophysiology of epilepsy. This study evaluated the antioxidant effects of daytime-restricted feeding (DRF) and the role of the Nrf2 signaling pathway in a lithium-pilocarpine model seizure model that induces status epilepticus (SE). We performed a lipoperoxidation assay and dihydroethidium fluorescence to measure oxidative stress markers in the hippocampus (malondialdehyde and reactive oxygen species). The protein content of Nrf2 and its downstream protein SOD2 was evaluated by Western blot. Cellular distribution of the Nrf2 and SOD2 proteins in the pyramidal cell layer of both CA1 and CA3 hippocampal subfields and astrocytes (GFAP marker) were quantified by immunofluorescence and immunohistochemistry respectively. Our results indicate that DRF reduced malondialdehyde levels and the production of reactive oxygen species. Furthermore, a significant increase in Nrf2 and SOD2 protein content was observed in animals subjected to restrictive diet. In addition, DRF increased the relative intensity of the Nfr2 fluorescence in the perinuclear and nuclear compartments of pyramidal neurons in the CA1 subfield. Nfr2 immunoreactivity and the astrocyte marker GFAP also increased their colocalization in DRF conditions. Also, SOD 2 immunoreactivity was increased in CA1 pyramidal neurons but not in CA3 region. Our findings suggest that DRF partially prevents oxidative stress by increasing the Nrf2 transcriptional factor and the SOD2 enzyme during the development of SE.

Keywords

daytime-restricted feeding; oxidative stress; status epilepticus; Nrf2; SOD2; hippocampus

Subject

Biology and Life Sciences, Neuroscience and Neurology

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