Effects of Zinc Deficiency and Supplementation on Hippocampal ZnT3, NOGO-A, IL-6, and SESN2 Expression and Oxidative Stress Markers in a Cuprizone-Induced Toxic Demyelination Model
- 1Department of Phsiology, Medical Faculty, Selçuk University, 42250 Konya, Türkiye
- 2Department of Medical Biology, Medical Faculty, KTO Karatay University, 42020 Konya, Türkiye
- 3Department of Phsiology, Medical Faculty, Istanbul Medipol University, 34810 Istanbul, Türkiye
Abstract
This study investigated the effects of zinc deficiency and supplementation on oxidative stress markers and the expression of ZnT3, NOGO-A, IL-6, and SESN2 in hippocampal tissue within a cuprizone (CPZ)-induced toxic demyelination model. Methods: Forty-six adult male Wistar rats were divided into five groups: Control (n = 6), Sham (n = 10), CPZ (n = 10), CPZ + zinc-deficient diet (n = 10), and CPZ + zinc supplementation (5 mg/kg/day, i.p., n = 10). Toxic demyelination was induced by continuous cuprizone administration for eight weeks. At the end of the experimental period, hippocampal malondialdehyde (MDA) and glutathione (GSH) levels were measured; additionally, hippocampal ZnT3, NOGO-A, IL-6, and SESN2 mRNA expression levels were analyzed using quantitative real-time PCR. Cuprizone administration led to significant hippocampal oxidative stress, characterized by increased MDA levels and decreased GSH concentrations (p < 0.05); these oxidative changes were further exacerbated in CPZ-treated animals fed a zinc-deficient diet (p < 0.05). Furthermore, CPZ-induced demyelination suppressed ZnT3 expression in hippocampal tissue while significantly increasing NOGO-A, IL-6, and SESN2 mRNA expression (p < 0.05). These molecular alterations were more pronounced in the zinc-deficient CPZ group (p < 0.05). Intraperitoneal zinc supplementation effectively mitigated these changes by suppressing oxidative stress, attenuating the upregulation of NOGO-A, IL-6, and SESN2 transcripts, and restoring ZnT3 expression to levels comparable to controls (p < 0.05). While dietary zinc deficiency exacerbated hippocampal oxidative stress, neuroinflammatory transcripts, and molecular markers associated with neurodegeneration in the cuprizone model, zinc supplementation restored oxidative balance; increased ZnT3 expression; and suppressed the upregulation of NOGO-A, IL-6, and SESN2. These findings suggest that zinc homeostasis significantly modulates cuprizone-induced hippocampal damage and that zinc supplementation may exert protective transcriptional and antioxidant effects during toxic demyelination.
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BibTeX
@article{atacak2026effects,
title = {{Effects of Zinc Deficiency and Supplementation on Hippocampal ZnT3, NOGO-A, IL-6, and SESN2 Expression and Oxidative Stress Markers in a Cuprizone-Induced Toxic Demyelination Model}},
author = {Adem Atacak and Elif Gulbahce-Mutlu and Gozde Acar and Saltuk Bugra Baltaci and Rasim Mogulkoc and Abdulkerim Kasim Baltaci},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209329},
url = {https://www.mdpi.com/1422-0067/27/20/9329},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Effects of Zinc Deficiency and Supplementation on Hippocampal ZnT3, NOGO-A, IL-6, and SESN2 Expression and Oxidative Stress Markers in a Cuprizone-Induced Toxic Demyelination Model
AU - Adem Atacak
AU - Elif Gulbahce-Mutlu
AU - Gozde Acar
AU - Saltuk Bugra Baltaci
AU - Rasim Mogulkoc
AU - Abdulkerim Kasim Baltaci
PY - 2026
DA - 2026/10/20
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209329
UR - https://www.mdpi.com/1422-0067/27/20/9329
AB - This study investigated the effects of zinc deficiency and supplementation on oxidative stress markers and the expression of ZnT3, NOGO-A, IL-6, and SESN2 in hippocampal tissue within a cuprizone (CPZ)-induced toxic demyelination model. Methods: Forty-six adult male Wistar rats were divided into five groups: Control (n = 6), Sham (n = 10), CPZ (n = 10), CPZ + zinc-deficient diet (n = 10), and CPZ + zinc supplementation (5 mg/kg/day, i.p., n = 10). Toxic demyelination was induced by continuous cuprizone administration for eight weeks. At the end of the experimental period, hippocampal malondialdehyde (MDA) and glutathione (GSH) levels were measured; additionally, hippocampal ZnT3, NOGO-A, IL-6, and SESN2 mRNA expression levels were analyzed using quantitative real-time PCR. Cuprizone administration led to significant hippocampal oxidative stress, characterized by increased MDA levels and decreased GSH concentrations (p < 0.05); these oxidative changes were further exacerbated in CPZ-treated animals fed a zinc-deficient diet (p < 0.05). Furthermore, CPZ-induced demyelination suppressed ZnT3 expression in hippocampal tissue while significantly increasing NOGO-A, IL-6, and SESN2 mRNA expression (p < 0.05). These molecular alterations were more pronounced in the zinc-deficient CPZ group (p < 0.05). Intraperitoneal zinc supplementation effectively mitigated these changes by suppressing oxidative stress, attenuating the upregulation of NOGO-A, IL-6, and SESN2 transcripts, and restoring ZnT3 expression to levels comparable to controls (p < 0.05). While dietary zinc deficiency exacerbated hippocampal oxidative stress, neuroinflammatory transcripts, and molecular markers associated with neurodegeneration in the cuprizone model, zinc supplementation restored oxidative balance; increased ZnT3 expression; and suppressed the upregulation of NOGO-A, IL-6, and SESN2. These findings suggest that zinc homeostasis significantly modulates cuprizone-induced hippocampal damage and that zinc supplementation may exert protective transcriptional and antioxidant effects during toxic demyelination.
SN - 1422-0067
ER -