NRF2 regulation in the developing brain cortex from rat offspring exposed to intrauterine and early postnatal zinc deficits
Year: 2025
Type: article
Abstract: Graphical abstract Abstract Objective Transcription factor NRF2, master regulator of the antioxidant response, is also involved in brain development. This paper investigated the role of NRF2 in developmental zinc deficiency-associated alterations in rat brain cortex: i) neurogenesis and ii) redox homeostasis. Methods Rat dams were fed a control or a marginal zinc diet (MZD) throughout gestation and until postnatal day 2 (P2). Offspring brain cortices were collected at the peaks of neurogenesis (embryonic day 14, E14) and astrogliogenesis (P2). mRNA levels of NRF2-dependent genes (Srxn1/SRXN1, Hmox1/HO-1, Cat/Catalase, Slc7a11/xCT, Pou5f1/OCT4, Nanog/NANOG, Gclc/GCLC, Gclm/GCLM, Abcc1/MRP1, and Ggt1/GGT1) were measured by qPCR, and glutathione content by reaction with 5,5′-dithiobis-(2-nitrobenzoic acid). Results In the E14 MZD brain cortex, Hmox1 and Gclc mRNA levels were higher (19 and 16%, respectively) and those of Nanog and Pou5f1 lower (32 and 34%, respectively), than controls. From E14 to P2, a 41–333% increase in expression of NRF2-dependent genes was observed in controls, which was less pronounced in MZD brains. At P2, mRNA levels of genes involved in H2O2 metabolism, i.e. catalase and glutathione production, were lower in MZD brain cortex compared to controls: Cat (27%), Gclc (20%), Gclm (24%), Ggt1 (51%) and Abcc1 (34%). Brain cortex total glutathione concentration was 19% lower in MZD than in controls. Conclusions NRF2 deregulation may not be a significant underlying mechanism of MZD-mediated altered neurogenesis. At P2, NRF2 downregulation significantly impaired the main cellular components that metabolize H2O2. Significance statement Maternal mild zinc deficiency during pregnancy can compromise the developing brain’s capacity to sustain normal redox homeostasis.
Source: Redox Experimental Medicine
DOI: 10.1530/rem-25-0013
Authors: Wei Zhu, Patricia I Oteiza
Institution: University of California, Davis
Language: English
Topic: Trace Elements in Health
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4414592539