Search

Recent findings suggest that gonadal steroid hormones are neuroprotective and may provide clinical benefits in delaying the development of Parkinson's disease. In this report we investigated the ability of oestradiol to protect mesencephalic dopaminergic neurones cultured in serum-free or serum-supplemented medium from toxicity induced by 6-hydroxydopamine or 1-methyl-4-phenylpyridinium ion (MPP[sup +]). The efficiency of both toxins and oestradiol was evaluated by tyrosine hydroxylase (TH) immunocytochemistry, [[sup 3]H]dopamine ([[sup 3]H]DA) uptake, length of dopaminergic processes and␣lactate dehydrogenase (LDH) release measurement. In␣cultures grown in serum-supplemented medium, a 2-h pre-treatment with high concentrations (10–100 µm) of 17β-oestradiol or 17α-oestradiol, the stereoisomer with weak oestrogenic activity, protected both dopaminergic and non-dopaminergic neurones from toxicity induced by 6-hydroxydopamine (6-OHDA; 40 or 100 µm) and by the high MPP[sup +] concentrations (50 µm) necessary to obtain significant neuronal death under those culture conditions. At these concentrations, MPP[sup +] was no longer selective for dopaminergic neurones but affected all cells present in the culture. In contrast, the hormonal treatments did not protect against selective degeneration of dopaminergic neurones induced by lower MPP[sup +] concentrations (below 10 µm), related to inhibition of complex I of respiratory chain. In cultures grown in serum-free medium, oestradiol concentrations higher than 1 µm induced neuronal degeneration and no protection against 6-OHDA or MPP[sup +] toxicity was observed at lower concentrations of the steroid. The neuroprotective effects of 17α- or 17β-oestradiol evidenced in this model might be due to the antioxidant properties of these compounds. However, other non-genomic effects of the steroids cannot be excluded. [ABSTRACT FROM AUTHOR]

Abstract Background In 2005, 84% of Wayana Amerindians living in the upper marshes of the Maroni River in French Guiana presented a hair mercury concentration exceeding the limit set up by the World Health Organization (10 μg/g). To determine whether this mercurial contamination was harmful, mice have been fed diets prepared by incorporation of mercury-polluted fish from French Guiana. Methods Four diets containing 0, 0.1, 1, and 7.5% fish flesh, representing 0, 5, 62, and 520 ng methylmercury per g, respectively, were given to four groups of mice for a month. The lowest fish regimen led to a mercurial contamination pressure of 1 ng mercury per day per g of body weight, which is precisely that affecting the Wayana Amerindians. Results The expression of several genes was modified with mercury intoxication in liver, kidneys, and hippocampus, even at the lowest tested fish regimen. A net genetic response could be observed for mercury concentrations accumulated within tissues as weak as 0.15 ppm in the liver, 1.4 ppm in the kidneys, and 0.4 ppm in the hippocampus. This last value is in the range of the mercury concentrations found in the brains of chronically exposed patients in the Minamata region or in brains from heavy fish consumers. Mitochondrial respiratory rates showed a 35–40% decrease in respiration for the three contaminated mice groups. In the muscles of mice fed the lightest fish-containing diet, cytochrome c oxidase activity was decreased to 45% of that of the control muscles. When mice behavior was assessed in a cross maze, those fed the lowest and mid-level fish-containing diets developed higher anxiety state behaviors compared to mice fed with control diet. Conclusion We conclude that a vegetarian diet containing as little as 0.1% of mercury-contaminated fish is able to trigger in mice, after only one month of exposure, disorders presenting all the hallmarks of mercurial contamination.

Purpose To investigate whether the chemokine CX3CL1 could play a role in the conjunctival inflammatory cell trafficking induced by an exposure to benzalkonium chloride (BAC). Methods Expression of CX3CL1 was assessed in BAC‐exposed human conjunctival cell (HCC)line using flow cytometry and RT‐PCR. In vitro migration of leukocytes to BAC‐stimulated HCCs was assessed by migration assays and immuno flow cytometry with or without inhibition of CX3CR1. In vivo inflammatory cell trafficking was investigated by immunohistochemistry and confocal microscopy in the conjunctiva of wild‐type or CX3CR1‐deficient mice exposed to BAC. Results BAC induced an overexpression of CX3CL1 in HCCs. Leukocyte chemotaxis was observed when HCCs are stimulated with BAC. Human monocytic cells (CD45+,CD14+) and NK cells (CD45+,CD56+) migration was inhibited by blocking the CXCR3 receptor. In a mouse model of BAC‐induced ocular surface toxicity, the inflammatory cell infiltration of the conjunctiva was altered in the CX3CR1‐deficient mice compared to wild‐type. Conclusion The CX3CL1/CX3CR1 axis is involved in the BAC‐induced conjunctival inflammation. Specific blockade of this receptor could regulate the cell trafficking in the ocular surface. [ABSTRACT FROM AUTHOR]