engleski

Gender-related differences in hepcidin and matallothionein I/II expression in spinal cord of iron-overloaded EAE rats

Introduction: Iron (Fe) is essential element for cellular functions but it can also participate in reactions that produce toxic reactive oxygen species. Recent researches show that disturbance of mechanisms that prevent harmful effects of Fe-induced oxidative stress may contribute to demyelinating process in multiple sclerosis (MS). To analyse those mechanisms we evaluated demyelinating changes and expression of metal-regulating proteins hepcidin and metallothionein I/II (MT I/II) in spinal cord (SC) tissue of Fe-overloaded (FeO) male and female Dark Agouti (DA) rats during the experimental autoimmune encephalomyelitis (EAE), an animal model that closely resembles MS. Since MS is more common among women than men, special attention was devoted to gender-related differences. Aim: To analyse the influence of metal-regulating proteins hepcidin and MT I/II on gender-related differences in demyelination process in iron-overloaded EAE rats. Material and methods: Male and female DA rats were treated by intraperitoneal injections of Fe–sucrose or saline for two consecutive weeks. 24 hours after the last injection animals were immunized by bovine brain homogenate in complete Freund's adjuvant. Untreated groups didn’t have any Fe or encephalitogen treatment. Animals were sacrificed 13 days after immunization and results were obtained in SC tissue by Kluver-Barrera staining, by immunohistochemistry and cell-based staining quantification. Results: The results show that male FeO EAE rats developed greater signs of demyelinating plaque formation in SC than female FeO EAE rats. Female EAE rats reacted on FeO by enhanced expression of hepcidin and MT-I/II in SC neurons in comparison to male rats. Conclusion: The data imply that harmful consequences during FeO and autoimmune attack might be partially restrained by Fe-regulated hormone hepcidin and by cytoprotective activities of MTI/II. Expression profiles of these proteins were different in male and female EAE rats exposed to FeO and this might have contributed to gender-related differences in demyelinating process. Funded by the University of Rijeka, Croatia (projects 13.06.1.1.16, 13.06.2.2.61 and 13.06.1.1.10).

iron ; experimental autoimmune encephalomyelits ; hepcidin ; metallothionein I/II ; spinal cord ; gender

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